Ziziphus jujuba

Scienti fi c Name Arabic: Annab, Aunnabe-Hindi, Aunnabehindi, Ennab, Unnab, Unab, Nabec, Nabig, Nabiq, Sidr, Ziziphus jujuba Miller. Zenzeli; Bangladesh : Bozoi, Kool, Kul; Brazil : Jujuba; Synonyms Burmese : Hsi:, Zee-Pen, Zi, Ziben, Zizidaw; Chines e: Da Zao, Beijing Mi Zao, Hei Zao, Hei Rhamnus lucidus Salisb., Rhamnus soporifer Tsao, Hong Zao, Hung Tzao, Peiching Mi Tzao, Lour., Rhamnus ziziphus L., Ziziphus jujuba var. Suan Zao Ren, Tzao, Wu He Hong Zao, Wu Ho spinosa (Bunge) Hu ex H. F. Chow, Ziziphus Hung Tzao, Zao, Zao Shu; nitida Roxb., Ziziphus sativa Gaertn., Ziziphus Czech : Cicimek Datlový, Čínská Datle, Jujuba; sinensis Lam., Ziziphus spinosa (Bunge) Hu ex F. Danish : Almindelig Jujube, Brystbærtræ; H. Chen, Ziziphus soporifer (Lour.) Schult., Dutch : Jujubeboom; Ziziphus vulgaris Lam., Ziziphus vulgaris var . Eastonian : Harilik Kreektürn; spinosa Bunge, Ziziphus zizyphus (L.) Meikle, Fiji : Ber; Zizyphus jujuba Mill. Finnish : Kiinanjujuba: French: Circoulier, Dattier De Chine, Guindanlier, Jujube De Chine, Jujubier, Jujubier Commun, Family Jujubier De Chin; German: Brustbeerbaum, Brustbeere, Chinesische Rhamnaceae Dattel, Chinesische Jujube, Domjujube, Jujube, Judendom, Rote Dattel; Greek : Tzintzola; Common/English Names Hungarian: Jujuba (Fa), Kínai Datolya, Zsidótövis; Chinese Date, Chinese-Date, Chinese Jujube, India : Boguri ( Assamese ), Boroi ( Bengali ), Chinese Plum, Chinese Red Date, Common Badara, Badari, Ber, Beri, Baer, Bor, Kath Ber Jujube, Jujube, Jujube Tree. (Hindu ), Badari, Bare, Bari, Barihannu, Ber, Bogare, Bogari, Bogori, Bogri, Bore, Egaci, Egasi, Elaci, Elachi, Elasi, Ilanji, Ilantai, Ilici, Vernacular Names Ilisi, Jati, Jelachi, , Karkandhu, Karkhandhyalachi, Yalachi-Hannuyagachi, Yalachi, Yelachi, Yelanji, Afghanistan : Berra ( Pashto ); Yelchi, Yellachi (Kannada ), Badaram, Badari,

T.K. Lim, Edible Medicinal and Non-Medicinal Plants: Volume 5, Fruits, 578 DOI 10.1007/978-94-007-5653-3_30, © Springer Science+Business Media Dordrecht 2013 Ziziphus jujuba 579

Elanta,Elantap-Pazham, Elantha, Elenda, Elentha, Russian : Kitajskij Finik, Unabi; Ilanta, Ilantha, Kolam, Lantaparintoddali, Slovašcina : Čičimak Navadni; Parintudai, Perimtoddali, Perintoddah, Perintutali, Spanish : Azufaifo, Azufaifo Chino, Jinjolero; Yelanda ( Malayalam ), Boroi ( Manipuri ), Bori, Thai : Bhud-Saar, Phutsaa Cheen; Bor, Baher, Ber, Bera, Bhor, Bora ( Marath i), Tibetan : Gya-Sug, Ko La, Rgya Sug; Borai, Kawl-Sun-Hlu ( Mizoram ), Ubhayakantaka Turkish : Hünnap; (Oriya ), Ajapriya, Badara, Badari, Balashta, Vietnamese : Táo, Táo Tàu . Dridhabija, Dviparni, Ghonta, Grddhanakha, Gudaphala, Kantaki, Karkarmadhu, Kola, Koli, Kuvali, Madhuraphala, Mahadebara, Nakhi, Origin/Distribution Nripabadari, Nripeshta, Phalashayshira, Prithukoli, Rajabadari, Rajakoli, Rajavallabha, Chinese jujube originated in China where they Sauvira, Srigalakoli, Sukrapriya, Sukshmapatrika, have been cultivated for more than 4,000 years. It Sukshmaphala, Suphala, Svachha, Tanubija, was distributed beyond China centuries ago and Ubhayakantaka, Vadari, Vatadalla (Sanskrit ), today it is cultivated to some extent in Russia, Adidaram, Atitaram, Attiram, Elandai, Elandei northern Africa, southern Europe, the Middle Vayr, Elandap-Pazham, Ilandai, Ilantai, Ilantai East, Caribbean and the southwestern United Ilai, Ilantai Ppalam, Ilandai Maram, Iradi, States. It is widely cultivated and naturalized in Iratti, Koli, Kondai, Korkoti, Kulari, Kullari, Eurasia. Kulavali, Kulvali Kol, Padari, Sivagam, Vadari, Vatari ( Tamil ), Badaramu, Badari, Badarika, Ganga-Regu-Pandu, Gangaregu, Gangarenu, Agroecology Karkandhuvu, Karkhanduvu, Ragu, Regi, Regu, Regu-Pandu, Renga, Rengha, Reni, Renu, Chinese jujube although a mild temperate species Reyghoo, Reygoo (Telugu) , Baer, Ber ,Annab, can withstand extremely hot, dry temperatures, Unab, Unnab ( Urdu ), Barholi, Bodokoli, Bodori, as well as cold temperatures down to −22°C. Koli ( Uriya ); Winter dormancy allows it to withstand tempera- Indonesia : Bidara, Dara, Widara; tures to subzero temperatures, yet it requires only Iran : Kanar, Kunar, Nabik; a small amount of winter chill in order for it to set Iraq : Aunnaberhindi, Nabig, Sidr; fruit. In its native range it is found in mountains, Italian : Giuggiole, Giuggiolo; hills, sunny dry slopes, plains and is also widely Japanese : Sanebuto Natsume; cultivated below 1,700 m. Chinese jujube is fairly Kampuchea : Putrea; adaptable, but should be grown in full sun as they Korean: Dae-Choo, Moet-Dae-Choo, Moettaec- are shade intolerant. It is rather drought tolerant hunamu; once established, but regular watering is impor- Laos : Than; tant to ensure optimum productivity. It is adapt- Malaysia : Bedara, Bedara Cina, Bidara, Epal able on a wide diversity of soils including saline Siam, Jujub, Langkeng; and alkaline soils but prefers a sandy-loamy, Nepal : Baer; well-drained soil. It does not perform well in Pakistan : Baryan, Singli, Unnab; heavy, poorly drained soils. Persian: Annab, Kanar, Kunar, Nabik, Sinpo-I- Jilani; Philippines: Manzanas, Mansanitas (Spanish ), Edible Plant Parts and Uses Mansanitas ( Tagalog ); Polish : Chiński Daktyl, Jujuba, Jujuba Mature near ripe and ripe fruits are eaten fresh, Pospolita; dried, preserved, boiled or pickled. Ripe fresh Portuguese : Açofeifeira; fruits as well as the dried candied fruit are eaten 580 Rhamnaceae as snack or in herbal teas. Chinese dates are avail- rice and boiled in a broth of Korean ginseng, able in dried, unsmoked red form called hóng zǎo dried seeded jujube fruits, garlic, and ginger. or in blacked smoked form called h ēi zǎo . A popular Chinese dish is chicken stewed with Smoking enhanced its fl avour. In Asian groceries Goji berries, red dates and shitake mushroom. store in America, Europe and Australia, four Other common, but noteworthy recipes include, types of preserved Chinese jujube are available: braised chicken red dates with bacon, pork, scal- two shrivelled with intact skin, the dull maroon lop and red dates soup, tomato and red date por- hóng zǎo (red jujube) (Plate 9 ) and the black h ēi ridge and Chinese jujube and cheddar strudel. zǎo (black jujube) and two scored skin sugar pre- Chinese jujube butter can be made by cooking serves the mi-z ǎo (honey jujube) and the seedless the ripe fruits with water, sugar and seasonings wu-he - zǎo (pitted jujube). Jujube powder and such as cinnamon, clove, nutmeg, lemon and vin- jujube oil are also processed from the fruit. egar. In Tamil Nadu, India, the dried fruits minus Poached jujubes can be added to fruit compotes. the seed are pounded with tamarind, red chillies, A candy called “jujube”, which is made from salt, and jaggery to make a dough and dried again. jujube paste, is available in the United States. In This is used to make delicious cakes such as ilan- China, Korea, and Taiwan, a sweetened or honey thai vadai or regi vadiyalu and in various dishes. tea syrup containing jujube pulps is available in A jujube honey is produced in the Atlas glass jars (Plate 10 ), and canned jujube tea or Mountains of Morocco. dried, pulverized jujube pulp in the form of tea- bags is also available. The honey or sweetened syrup when diluted with cold water makes a Botany refreshing and nutritious drink. Jujube juice made from preseed jujubes and jujube vinegar from A small, deciduous, erect tree, 5–10 m high, fermented fruits are also available. In China, a spinose or unarmed with brown to gray-brown wine made from fermented jujubes called hong bark (Plate 1) and spreading often drooping zao jiu . The ripe fruits are sometimes preserved branches. Suckers frequently arise from the roots by storing in a jar fi lled with Chinese liquor near the trunk. Young branchlets gray brown or which allows them to store longer over the win- green, fl exuose, zig-zag with or without 2 stipular ter, such jujubes are called jiu zao (spirited spines (Plate 2 ). Stipular spines slender, caducous jujubes). In West Bengal and Bangladesh, the long spines erect, to 3 cm, stout; short spines fruits are pickled. In Vietnam and Taiwan, fully recurved. Petioles 1–6 mm, glabrous. Leaves mature near ripe fruits are harvested and sold in alternate, dark green above, pale green below, the local markets and also exported to other ovate, ovate-elliptic, or elliptic-oblong, 3–7 × southeast Asian countries (Plates 5 , 6 , 7, and 8 ). 1.5–4 cm, papery, 3- veined from base, base They are crispy, sweet and delicious. slightly asymmetric, obtuse, margin crenate-ser- Jujubes fresh or the dried are relished in an rate, apex obtuse or rounded, rarely acute array of Asian culinary cuisines – food dishes (Plates 2 , 3 , and 4 ). Flowers yellow-green, fra- and desserts. Dried, candied jujubes can added to grant, bisexual, pentamerous, glabrous, solitary cakes and other desserts, soups, stews, or or 2–8 clustered in axillary cymes, shortly pedun- stuffi ngs; or substituted in recipes that call for culate (Plates 2 , 3 , and 4 ). Pedicel 2–3 mm; sepals raisins or dates In Vietnam, the dried fruits are ovate triangular distinctly keeled below; petals used in desserts such as sâm bổ lượng, a cold obovate, clawed at base, disk orbicular, fl esh and beverage that comprised the dried jujube, longan, 5-lobed; ovary basally slightly immersed in disk; fresh seaweed, barley, and lotus seeds. In Korea, style 2 connate halfway. Drupe green in colour, jujubes are featured in the popular ginseng but as it ripens it goes through a yellow-green chicken dish called samgyetang . To prepare the stage becoming red or red-purple at maturity, dish, whole young chicken is stuffed with glutinous subglobose, oblong, ellipsoid, or narrowly ovoid, Ziziphus jujuba 581

Plate 1 Old jujube tree with gray-brown bark and droop- ing branches

Plate 4 Fertilised fl owers with very young fruits

Plate 2 Flowering, drooping branches

Plate 5 Harvested mature, unripe fruits

Plate 3 Close-up of leaves and greenish-yellowish fl owers

2.5–5 cm by 2–3.5(–4.5) cm in diameter (Plates 5 , Plate 6 Close-up of mature fruit 6 , 7 , and 8 ); mesocarp fl eshy, thick, sweet to acid-sweet; stone acute or obtuse at both ends, Nutritive/Medicinal Properties 2-loculed, 1- or 2-seeded (Plate 8 ); fruiting pedicel 2–5 mm or longer. Seeds compressed- Food value of raw, Chinese jujube fruit per 100 g orbicular, 10 × 8 mm. edible portion was reported as follows (USDA 582 Rhamnaceae

Plate 7 Crispy white fl esh and one seeded

Plate 9 Dried, red ripe jujubes, hóng z o

Plate 8 Ripe jujbe fruits

2012) : water 77.86 g, energy 79 kcal (331 kJ), pro- tein 1.20 g, total lipid (fat) 0.20 g, ash 0.51 g, car- bohydrate 20.23 g; minerals – calcium 21 mg, iron 0.48 mg, magnesium 10 mg, phosphorus 23 mg, potassium 250 mg, sodium 3 mg, zinc 0.05 mg, copper 0.073 mg, manganese 0.084 mg; vitamins – vitamin C (total ascorbic acid) 69 mg, thiamin 0.020 mg, ribofl avin 0.040 mg, niacin 0.900 mg, vitamin B-6 0.081 mg, and vitamin A 40 IU (2mg Plate 10 Bottle of honey jujube tea concentrate RAE). Ripe Ziziphus jujuba fruit contained 42.25% water and 44.0% soluble solids (Vidrih et al. 2008 ) . (Guil-Guerrero et al. 2004 ) . The main fatty acids Mesocarp contained on dry matter basis 1.1% pro- were 12:0 (18.3%), 10:0 (12.5%), 18:2n6 teins, 0.73% total phenols and 1.7% of ash, 12.4% (9.27%), 16:1n7 (8.50%), 16:0 (7.25%), and of insoluble and 6.7% of soluble fi bres, 36.5.0% 18:1n9 (5.34%) on total saponifi able oil. The glucose, 33.4% fructose and 0.22% sucrose, fruits yielded 1.33/100 g saponifi able oil on a dry 83.8 mg/100 g ascorbic acid and 39.4 mg/100 g weight basis. Fatty acid profi les of fruits were dehydro ascorbic acid. Jujube seeds contained found to be in fl uenced by their developmental 2.5% total fat. stage. Carotenes were found to be in good Triglycerides having medium-chain fatty acids agreement with other fruits, varying from 4.12 to were most abundant in the Spanish varieties studied 5.98 mg/100 g on a dry weight basis. The Ziziphus jujuba 583

contribution to vitamin value reach a medium of (3), 3- O- trans - p -coumaroyl alphitolic acid (4), 38 m g RE/100 g on a fresh weight basis. betulinic acid (7), betulonic acid (9); and oleanane- Food value of dried, Chinese jujube fruit per type triterpenes: 3-O-cis-p- coumaroyl maslinic 100 g edible portion was reported as follows acid (5), 3-O-trans-p -coumaroyl maslinic acid (USDA 2012 ) : water 19.70 g, energy 287 kcal (6), oleanolic acid (8), oleanonic acid (10) (Lee (1,202 kJ), protein 3.70 g, total lipid (fat) 1.10 g, et al. 2004a, b ) . ash 1.90 g, carbohydrate 73.60 g; minerals – cal- Jujube fruit were a good source of phenolics cium 79 mg, iron 1.80 mg, magnesium 37 mg, (especially fl avonoids), comparable to prunes, phosphorus 100 mg, potassium 531 mg, sodium and therefore should be recommended by nutri- 9 mg, zinc 0.19 mg, copper 0.265 mg, manganese tionists to be part of our diet (Hudina et al. 0.305 mg; vitamins – vitamin C (total ascorbic 2008 ) . Two phenolic acids from the hydroxycin- acid) 13 mg, thiamin 0.210 mg, ribo fl avin namate sub-class (chlorogenic acid and caffeic 0.360 mg, and niacin 0.500 mg. acid) and three fl avonoids (catechin, epicatechin and rutin) were found in the fruit of seven Chinese jujube cultivars. Acid jujube fruit had Other Fruit Phytochemicals the highest content of hydroxycinnamic acids, as well rutin and epicatechin, while ‘Zizao’ had Guanosine 3¢ : 5 ¢ -monophosphate was identi fi ed the highest catechin content. One new cean- in Z. jujube fruit and its content increased 90-fold othane-type triterpene and one new sesquiter- during fruit ripening (Cyong and Takahashi pene, together with two known triterpenes, 1982 ) . Zizyphus-pectin A from Ziziphus jujuba zizyberanalic acid and ursolic acid were isolated fruits contained O -acetyl groups located at from the fruits of Ziziphus jujuba (Guo et al. positions 2,3,6 of the 2,3,6 tri-O acetylated 2009b) . The structures of two new compounds D-galactopyranosyl residues in galactan side were elucidated as 2a -aldehydo-A(1)-norlup- chains (Tomoda et al. 1985 ) . Daechualkaloid-A a 20(29)-en-27,28-dioic acid (zizyberanal acid), new pyrrolidine alkaloid was found in the fruit of and zizyberanone. Ten triterpenoid acids (cean- Z. jujube ( Han et al. 1987 ) . Seventy eight volatile othic acid, alphitolic acid, zizyberanal acid, compounds were identifi ed in the fruit of zizyberanalic acid, epiceanothic acid, ceanoth- Z. jujuba var. inermis among which aliphatic acids enic acid, betulinic acid, oleanolic acid, ursonic and carbonyl compounds accounted for 62.97 acid and zizyberenalic acid) were identifi ed in and 29.56% of total volatiles respectively (Wong the dried fruit of Ziziphus jujuba which has been et al. 1996 ) . The major constituents were decanoic widely used as one of the traditional Chinese acid (19.98%) and dodecanoic acid (15.64%). medicines (TCMs) (Guo et al. 2009a ) . Guo et al. Eleven triterpenoids, namely colubrinic acid (2010a ) found that the contents of triterpenic (0.74%), alphitolic acid (0.09%), 3-O-cis-p - acids in the fruits of Ziziphus jujuba var. spinosa coumaroyl alphitolic acid (0.19%), 3-O-trans - were higher than those in the fruits of Z. jujuba , p-coumaroyl alphitolic acid (0.19%), 3-O-cis-p - especially for the compound pomonic acid. coumaroyl maslinic acid (0.08%), 3-O-trans - The fruit of Ziziphus jujube contains p-coumaroyl maslinic acid (0.08%), betulinic zizybeoside II, the content ranged from 0.013 to acid (0.41%), oleanolic acid (0.05%), betulonic 0.041% (Niu et al. 2008 ) . Five compounds were acid (0.50%), oleanonic acid (0.59%) and zizy- isolated from Ziziphus jujuba var. spinosa and berenalic acid (0.19%) were isolated quantita- their structures were established as jujuboside D, tively from Ziziphus jujube (Lee et al. 2003 ) . jujuboside A, 5,7,4¢ -trihydroxy fl avonol-3-O -b - Eleven triterpenoides were isolated from the D -rhamnopyra nosy l-(1 → 6)-b -D -glucopyrano- fruits of the Zizyphus jujuba : ceanothane-type side, 6 ¢ ″-coumaroylspinosin and phenylalanine triterpenes: colubrinic acid (1), zizyberenalic (Liu et al. 2004 ) . Ziziphus jujuba alcoholic fruit acid (11); lupane-type triterpenes: alphitolic extract was found to contain 0.013 mg myricetin/ acid (2), 3-O-cis-p -coumaroyl alphitolic acid mL extract, 0.057 mg kaempferol/mL extract and 584 Rhamnaceae

0.030 mg rutin/mL extract (Cacig et al. 2006 ) . var. spinosu s (Shibata et al. 1970 ) . Acid hydrolysis Twelve fl avonoid compounds from methanol fruit of the saponin of the seeds of Zizyphus jujuba extracts of Zizyphus jujuba and Zizyphus spina- afforded ebelin lactone, which yielded the christi were identi fi ed as quercetin, kaempferol, sapogenin, jujubogenin, on Smith-de Mayo and phloretin derivatives (Pawlowska et al. 2009 ) . degradation (Kawai et al. 1974 ) . Enzymatic Zizyphus jujuba showed a content of fl avonoids than hydrolyses of jujubosides A and B, the saponins Z . spina-christi. Nine nucleosides and nucleobases of the seeds of Zizyphus jujuba, afforded prosa- in 49 jujube samples from 43 cultivars from 26 cul- pogenins I, II and III (Otsuka et al. 1978 ) . tivation regions were characterised and quantifi ed Sanjoinine-A (frangufoline), nuciferine and their (Guo et al. 2010b ) . In g/100 g dry weight, total free congeners were found in the seeds of Zizyphus amino acid content ranged from 5.2 to 9.8 g, total vulgaris var. spinosus (Han and Park ( 1987a ) . phenolic content measured by Folin–Ciocalteu A C-glycosyl fl avane named spinosin (2″- O- b - ranged from 1.1 to 2.4 g and fl avonoids ranged from glucosylswertisin) and its acylated derivatives 0.7 to 1.8 g in the fruit pulp of Korean Z. jujuba cul- and swertisin isolated from the seeds (Woo et al. tivars (Choi et al. 2011 ) . Jujube fruits contained the 1979 ) . Three acylated fl avone-C-glycosides, following fl avonoids: procyanidin B2, epicatechin, namely 6‴-sinapoylspinosin, 6‴-feruloylspinosin quercetin-3-O -rutinoside (Q-3-R), quercetin-3-O- and 6‴- p-coumaroylspinosin) were identifi ed galactoside (Q-3-G), kaempferol-glucosyl- from Z. jujuba seeds (Woo et al. 1980 ) . From rhamnoside (K-G-R), and two unidentifi ed the methanol fraction of jujube seeds (Suan Zao compounds. Ren), triterpenoid saponins, jujuboside B and A novel water-soluble polysaccharide (ZSP3c) jujuboside A, phenolic acid, ferulic acid and a was isolated from Zizyphus jujuba cv. Jinsixiaozao fl avonoid compound, spinosin were isolated (Li et al. 2011b ) . ZSP3c was composed of (Zeng et al. 1987 ) . A new fl avonoid compound L-rhamnose, D-arabinose and D-galactose in a named zivulgarin, 4″- b -D-glucopyranosyl swer- molar ratio of 1:2:8. The main backbone chain of tisin, was also found. ZSP3c comprised (1 → 4)-D-galacturonopyranosyl From seeds of Zizyphus vulgaris var. spinosus residues interspersed with (1 → 2)-L-rhamno a cyclic peptide, sanjoinenine, four new peptide pyranosyl residues and (1 → 2,4)-L- alkaloids (sanjoinine-B, -D, -F and -G2), together rhamnopyranosyl residues. with the known cyclic peptide alkaloids, frangu- Guo et al ( 2011a ) found ultra-high-perfor- foline and amphibine-D were isolated (Han et al. mance liquid chromatography (UHPLC)-TOFMS 1990) . From the seeds of Zizyphus vulgaris var. coupled with multivariate statistical analysis spinonus, aporphine alkaloids: nuciferine, method to be a powerful technique for rapid study N-methylasimilobine, nornuciferine, norisocory- of differentiating components between two dine, caaverine and tetrahydrobenzylisoquinoline Ziziphus species, (Z. jujuba and Z. jujuba var. alkaloid: (+)-coclaurine were isolated and spinosa ). By comparing the mass/UV spectra identi fi ed. Zyzyphusine, a new quaternary apor- and retention times with those of reference phinium alkaloid from butanol soluble fraction compounds, these components were fi nally was isolated and characterized. characterized as zizyberenalic acid, palmitoleic New dammarane-type triterpene oligoglyco- acid, oleic acid, pomonic acid and rutin, and these sides, jujubosides A1 and C and acetyljujuboside compounds would be the potential chemical mark- B1 were isolated from Zizyphus jujuba var. ers for discrimination of these jujube products. spinosa seeds, together-with three known saponins (Yoshikawa et al. 1997 ) . Following the elucidation of jujubosides A1 and C and acetylju- Seed Phytochemicals juboside B1, novel protojujubogenin type triter- pene bisdesmosides, protojujubosides A, B, and Ebelin lactone was obtained on hydrolysis of the B1, were isolated from Zizyphus jujuba var. saponin fraction of the seeds of Zizyphus jujuba spinosa seeds (Matsuda et al. 1999 ) . Ziziphus jujuba 585

Eight fl avonoid compounds were isolated acid content ranged from 4.0 to 5.3 g, total from the seeds of Ziziphus jujuba var. spin phenolic content measured by Folin–Ciocalteu osa and elucidated as swertish (1), puerarin ranged from 3.6 to 4.6 g and fl avonoids ranged (2), 6‴-feruloylspinosin (3), apigenin-6-C-b -D- from 3.2 to 4.0 g in the seed of Korean Z. jujube glucopyranoside (4), spinosin (5), 6‴-feruloylisos- cultivars (Choi et al. 2011 ) . Seeds contained the pinosin (6), isospinosin (7), and isovitexin-2 following fl avonoids: saponarin, spinosin, vitexin, -O - b -D-glucopyranoside (8) (Cheng et al. 2000 ) . swertish, 6‴-hydroxybenzoylspinosin (6‴-HBS), Jujuphenoside and jujuphenoside were isolated 6‴-feruloylspinosin (6‴-FS), and one unidenti fi ed from the seeds of Ziziphus jujuba var. spinosa substance. together with 22 known compounds (Li et al. 2005b ) . A furanofl avonol rhamnoside named spinorhamnoside was isolated from the of Ziziphus Leaf Phytochemicals jujuba var. spinosa seeds (Wang et al. 2005 ) . the triglyceride, 1,3-di-O -[9(Z)-octadecenoyl]-2- O - Terephthalic acid and its methyl esters were [9(Z),12(Z)-octadecadienoyl]glycerol (3), and found in the leaves and stems of Zizyphus sativa a fatty acid mixture of linoleic, oleic and stearic (Thakur et al. 1975 ) . The alkaloids coclaurine, acids, were found to be the major active compo- isoboldine, norisoboldine, asimilobine, iusi- nents in Z. jujuba seeds (Su et al. 2002 ) . A new phine iusirine and juziphine and juzirine juzi- pentacyclic lupane-type triterpene derivative, phine and juzirine were isolated from Z. jujuba 3-O -[9(Z)-octadecenoyl]betulinic acid and betu- leaves by (Ziyaev et al. 1977 ) . Juziphine had the linic acid were also isolated. Eleven major com- structure of 8-hydroxy-1R-(4 ¢ -hydroxybenzyl)- ponents of 2 saponins and 9 fatty acids, namely 7-methoxytetrahydroisoquinoline, and juzirine jujuboside A, jujuboside B, lauric acid, myris- that of 7-hydroxy-1-(4¢ -hydroxybenzyl)-6-methoxyi- tic acid, palmitic acid, palmitoleic acid, stearic soquinoline. A damarane-type saponin was iso- acid, oleic acid, linoleic acid, arachidic acid and lated from the leaf and stem of Z. vulgaris and docosanoic acid were identifi ed in the seeds of assigned as 3-O -[(2- o-a-1)-fucopyranosyl-3-O- Ziziphus jujuba (Suanzaoren) (Zhao et al. 2006 ) . b-1(-glucopyranosyl)-a-L-arabinosyl] jajubo- Saponins and fatty oil contains several fatty acids genin (Ikram et al. 1981 ) . Ziziphin an antisweet in Suanzaoren were responsible for its thera- compound was found in the leaves (Kennedy and peutic activities. Other alkaloids, terpenoids and Halpern 1980 ) and elucidated as 3-0-(4-0-a -L- saponins were also found. A new keto-dammarane rhamnopyranosyl- a -L-arabinopyranosyl)-20-0- type of saponin jujuboside G(1), along with three (2,3- di-0-acetyl)-a -L-rhamnopyranosyljujubo- known triterpene saponins,jujuboside A(2), juju- genin (Kurihara et al. 1988 ) . Three new jujubo- boside B(3) and jujuboside A1 (4), were isolated genin glycosides, jujubasaponins I–III were from the seeds of Zizyphus jujuba var. spinos a isolated from the fresh leaves of Zizyphus jujuba , (Wang and Yang 2008 ) . Zhang et al. ( 2008 ) (Yoshikawa et al. 1991 ) . developed a reverse phase high performance liq- Sixteen compounds were isolated from the uid chromatography-evaporative light scattering leaves of Ziziphus jujuba: 8 monomeric catechins detection for the simultaneous determination of -(−)-epiafzelechin, (−)-epicatechin, (−)-epigallo- jujuboside A, B and betulinic acid in jujube seeds. catechin, (−)-epicatechin gallate, (−)-epigal-locat- Seven compounds were isolated from the seeds echin gallate, (+)-catechin, (+)-catechin gallate, of Ziziphus jujuba var. spinosa (Bai et al. 2003 ) . and (+)-gallocatechin; 4 dimeric proanthocyani- Their structures were established as jujuboside E dins – (−)-epiafzelechin-(4b -8)-(−)-epicatechin, (1), jujuboside B (2), jujuboside A (3), betulic acid proanthocyanidin B-2, (−)-epicatechin-(4b -8)- (4), stearic acid (5), sucrose (6) and inosine (−)-epigallocatechin, and (−)-epiafzelechin- (7). A new cyclopeptide alkaloid, jubanine-E, (4 b -8)-(−)-epigallocatechin; and 4 oligomeric was isolated from Zizyphus jujube (Pandey et al. proanthocyanidins consisting of epiafzelechin, 2008a ) . In g/100 g dry weight, total free amino epigallocatechin, catechin, and epicatechin with 586 Rhamnaceae different degrees of polymerization (Malik et al. isolated from the stem bark of Zizyphus sativa 1997 ) . (Singh et al. 2006 ) . A cyclopeptide alkaloid, sati- Fourteen constituents including three vanine-M (1), together with known alkaloid fl avonoids, two saponins and nine triterpenic nummularine-P were isolated from Zizyphus acids were identifi ed from Ziziphus jujuba and sativa stem bark (Pandey et al. 2008b ) . Z. jujuba var. spinosa leaves and characterized Sixteen compounds were isolated from (Guo et al. 2011b ) . This included: quercetin-3-O- the bark of Ziziphus jujuba : 8 monomeric rutinoside, zizyphus saponins I and II, ceanothic catechins -(−)-epiafzelechin, (−)-epicatechin, acid, alphitolic acid, maslinic acid, 2 a-hydroxyur- (−)-epigallocatechin, (−)-epicatechin gallate, solic acid, zizyberanalic acid, epiceanothic acid, (−)-epigal-locatechin gallate, (+)-catechin, ceanothenic acid, betulinic acid, and oleanolic (+)-catechin gallate, and (+)-gallocatechin; 4 acid. dimeric proanthocyanidins – (−)-epiafzelechin- (4 b -8)-(−)-epicatechin, proanthocyanidin B-2, (−)-epicatechin-(4b -8)-(−)-epigallocatechin, and Stem Bark Phytochemicals (−)-epiafzelechin-(4b -8)-(−)-epigallocatechin; and 4 oligomeric proanthocyanidins consisting From the stem bark of Z. jujuba , cyclopeptide of epiafzelechin, epigallocatechin, catechin, and alkaloids: mauritine-A, mucronine-D, amphib- epicatechin with different degrees of polymeriza- ine-H, nummularine-A, nummularine-B and tion (Malik et al. 1997 ) . The pentameric proan- jubanine-A and -B were isolated (Tschesche et al. thocynidine called proanthocyanide PZ-5 was 1976 ) . From the bark of Zizyphus sativa , 14-mem- isolated from the bark and its structure elucidated bered ring cyclopeptide alkaloids: sativanine-A as (−)-epiafzelechin-(4b -8)-(−)epigallocatechin- (1) and sativanine-B (2), were isolated; com- (4 b-8)-(+)-catechin-(4 a -8)-(−)-epigallocatechin- pound 1 belonged to the integerrine type, while 2 (4 b -8)-(+)-catechin (Malik et al. 2002 ) . A new was similar to nummularine-G with an additional cyclopeptide alkaloid, jubanine-C (1), together ring in the side chain (Tschesche et al. 1979 ) . with known alkaloids scutianine-C (4) and zizy- From the bark of Zizyphus sativa a 13 membered phine-A (5), were isolated from the stem bark of cyclopeptide alkaloid, sativanine-C was isolated Zizyphus jujuba (Tripathi et al. 2001 ) . (Shah et al. 1984a ) . A damarane-type saponin was isolated from the stem of Z. vulgaris and assigned as 3-O -[(2- o -a-1)-fucopyranosyl-3- O - Root Phytochemicals b-1(-glucopyranosyl)-a-L-arabinosyl] jajubo- genin (Ikram et al. 1981) . From the bark of A lanostane-type triterpene, zizyphulanostane- Zizyphus sativa two 13 membered cyclopeptide 21-oic acid, and a terpenic d-lactone, zizyphu- alkaloids were isolated, sativanine-C (Shah et al. lanostan-18-oic acid, were isolated from the roots 1984a ) and sativanine-G (Shah et al. 1984b ) . of Zizyphus vulgaris and characterized From the bark of Zizyphus sativa , a 13-membered as lanosta-25 (26)-en-9a -ol-21-oic acid cyclopeptide alkaloids were isolated sativanine- and lanosta-25 (26)-en-22b -ol-18-oic acid D (1) (Shah et al. 1985a ) , sativanine-F (Shah 3(19)-olide, respectively (Mukhtar et al. 2004 ) . et al. 1985b ) , Sativanine-E (Shah et al. 1985c ) , A novel pentacyclic triterpenoid, zizyberanalic sativanine-H (Shah et al. 1986 ) , and sativanine- acid, was isolated from both bark and roots of K, a 13-membered N -formyl cyclopeptide alka- Zizyphus jujuba and elucidated as 3 a-hydroxy- loid containing a short side chain (Shah et al. 2 b -aldehydo-A(1)-norlup-20(29)-en-28-oic acid 1987 ) . The 14-membered cyclopeptide alkaloid (Kundu et al. 1989 ) . mauritine-C and the 13-membered cyclopeptide Three triterpene esters: 2-O -protocatech- alkaloid sativanine-C were isolated from Zizyphus uoylaliphitolic acid, 2a -hydroxypyracrenic acid sativa (Shah et al. 1989b ) . Two cyclopeptide and 3-O -protocatechuoylceanothic acid were iso- alkaloids, sativanine-N and sativanine-O were lated from the water-insoluble fraction of the Ziziphus jujuba 587 ethanol extract of Zizyphus jujuba var. spinosa radical concentration by 50%), FRAP and TEAC root (Lee et al. 1996 ) . values of the peel and pulp were remarkably Pectic polysaccharides were found to be the correlated to their total phenolic contents major components in all water-soluble polysac- (R2 = −0.922, R2 = 0.985 and R 2 = 0.997, respectively). charides (WSPs) in Chinese jujube leaves, fruits The results indicated that the high capacity of anti- and fl owers (Zhao et al. 2008 ) . oxidant of Chinese jujube fruit could be attributed to the high phenolic contents in the fruit. Studies showed that jujube peel of all cultivars Antioxidant Activity had the highest antioxidant capacities, refl ecting the highest content of total phenolics, fl avonoids, Studies showed that extracts of six kinds of com- and anthocyanins found in this part (Zhang et al. mon food including Ziziphus jujuba , could scav- 2010 ) . Further, the predominant phenolic acid in enge (O2 ) free radical, inhibit lipid peroxidation jujube was found to be protocatechuic acid, fol- of mice liver homogenate (in vivo and in vitro), lowed by gallic acid, chlorogenic acid and caffeic decrease hyaluronic acid depolymerization acid. The results clearly indicated Chinese jujube induced by (O2 ), and inhibit the adenosine deami- to have signifi cant potential to use as a natural nase activity of mice liver homogenate (in vivo) antioxidant agent. (Wang and Chen 1991 ) . These actions were very One neutral polysaccharide fraction (ZJPN) and similar to the actions of those traditional Chinese three acidic polysaccharide fractions (ZJPa1, ZJPa2 tonic prescriptions and their individual herbal and ZJPa3) with the average MW ranging from drugs studied earlier. 40,566 to 129,518 Da were isolated from jujube Results of studies indicated that the antioxi- fruit (Chang et al. 2010 ) . Six monosaccharides, dant capacity differed in the fi ve Chinese jujube namely, rhamnose, arabinose, xylose, mannose, cultivars (Li et al. 2005a ) . The antioxidant activi- glucose and galactose were present in polysaccha- ties, scavenging effect on the 2,2-diphenyl-1-py- ride fractions. The galacturonic acid content in cril-hydrazyl (DPPH) radical and reducing power polysaccharide fractions followed the order: of extracts decreased in the order of ZJPa3 > ZJPa2 > ZJPa1 > ZJPN. All the four poly- Z. jujuba cv. jinsixiaozao, Z. jujuba cv. yazao, saccharide fractions were found to be more effec- Z. jujuba cv. jianzao, Z. jujuba cv. junzao, tive in scavenging superoxide anions than hydroxyl Z. jujuba cv. sanbianhong. The antioxidant activ- radicals, while acidic polysaccharides showed a ities of extracts from cv. jinsixiaozao, cv. yazao more pronounced effect in chelating ferrous ion. and cv. jianzao were stronger than a-tocopherol. Geographical condition was found to impact Signi fi cant differences were found between on the antioxidant levels in Ziziphus jujuba var. a -tocopherol and both Z. jujuba cv. jinsixiaozao spinosa (Sun et al. 2011 ) . Jujube fruits exhibited and Z. jujuba cv. yazao, while no signi fi cant dif- signi fi cant DNA damage protection activity and ferences were found between a -tocopherol and in-vitro antiradical potentials. Correlation analyses Z. jujuba cv. jianzao. Additionally, no correlation indicated that both altitude and annual precipita- was found between total phenolic contents and tion exerted profound effects on natural antioxi- antioxidant capacities of extracts from fi ve culti- dant levels. Jujube fruits in arid harsh and vars. Contrariwise, high correlation was found high-altitude areas were found to accumulate between phenolic content and antioxidant capac- higher levels of natural antioxidants and to dis- ity in another study. The total phenolic content in play stronger antioxidant activities. peel was fi ve to six times higher than that in the pulp of all the three Chinese jujube cultivars (Z. jujuba cv. mayazao, Z. jujuba cv. dongzao and Z. Antisweet Activity jujuba cv. yuanzao) (Xue et al. 2009 ) . The pheno- lics contents in the jujube were different among An aqueous ethanol extract of Ziziphus jujuba cultivars. The EC50 (concentration of lyophilized leaves was fractionated into two components – samples needed to decrease the initial DPPH ZjE-A, which had surface active properties, and 588 Rhamnaceae

ZjE-B, which did not. Bioassay by psychophysical weight of Ehrlich Ascites Cancer mice (Wang et al. tests on humans revealed sweetness-modifying 1995) . The seed oil also displayed antineoplastic activity in ZjE-A, but not in ZjE-B. ZjE-A the effects on Ehrlich Ascites cancer mice. Among potent, purifi ed component, was found to con- 11 triterpenoic acids isolated from the fruits of sist of 60–80% ziziphins, triterpene saponin Zizyphus jujuba , the lupane-type triterpenes, glycosides (Kennedy and Halpern 1980 ) . One such as compounds 3- O-cis-p-coumaroylalphi- of the fractions obtained from the extract of tolic acid (3), 3- O-trans-p-coumaroylalphitolic Zizyphus jujuba leaves suppressed the response acid (4), 3- O-cis-p-coumaroylmaslinic acid, of the chorda tympani to sucrose, both in the 3- O-trans-p-coumaroylmaslinic acid, betu- rat and hamster (Yamada and Imoto 1987 ) . In linic acid (7), oleanolic acid, betulonic acid (9), the rat and man, the inhibitory effect was found showed high in-vitro cytotoxic activities against to be signifi cant in responses to various sugars K562 (human erythromyeloblastoid leukemia), and arti fi cial sweeteners but not in some sweet B16(F-10) (murine melanoma), SK-MEL-2 amino acids. The sweetness inhibiting substance (human skin melanoma), PC-3 (human prostate (ziziphin) contained in Z. jujuba leaves was cancer), LOX-IMVI (human melanoma), and elucidated as 3-0-(4-0-a -L-rhamnopyranosyl- A549 (human lung adenocarcinoma) tumour cell a -L-arabinopyranosyl)-20-0-(2,3- di-0-acetyl)- lines (Lee et al. 2003 ) . In particular, the cytotoxic a -L-rhamnopyranosyljujubogenin (Kurihara activities of 3-O-p -coumaroylalphitolic acids et al. 1988 ) . Ziziphin suppressed the sweetness (compounds 3 and 4) were better than those of induced by D-glucose, D-frutose, stevioside, gly- non-coumaroic triterpenenoids (compounds 7 cine, sodium saccharin, aspartame and naringin and 9). These results suggested that the couma- dihydrochalcone. Ziziphin however showed no royl moiety at the C-3 position of the lupane-type suppressive effect on the sour taste of hydrochlo- triterpene may play an important role in enhanc- ric acid and the bitter taste of quinine indicating ing cytotoxic activity. it to be highly specifi c to sweet taste (Kurihara Studies showed that the chloroform fraction of 1992) . Ziziphin was found to inhibit the sweet Z. jujuba fruit extract CHCl(3)-F induced a con- taste receptors in humans (Smith and Halpern centration dependent effect on apoptosis and a 1983) . Sweetness was reduced after either a 10 s differential cell cycle arrest in human hepatoma or a 90 s whole mouth treatment with ziziphins, HepG2 cells (Huang et al. 2007 ) . Apoptosis, an but not after quinine sulfate or apple juice con- increase in intracellular ROS (reactive oxygen trol treatment. The reduction in sweetness was species) level, a decline of mitochondrial mem- weak with 10 s 3.5% W/V ziziphin treatment, brane potential at low Z . jujuba concentrations, but strong after 90 s 0.88% W/V ziziphin treat- and a ROS-independent mitochondrial dysfunction ment; duration of suppression was about. 70 s. pathway at high concentrations were all observed. On comparison with known gymnemic acids, CHCl(3)-F-induced G1 arrest in HepG2 cells was effects suggested that net dissociation of ziz- associated with an increase in hypohosphoryla- iphins from taste receptor membranes and/or tion of Rb and p27(Kip1), and a decrease of inactivation in the membrane may be much faster phosphorylated Rb. Subsequent studies showed than with gymnemic acids. Three new jujubo- that that combination of the chloroform fraction genin glycosides, jujubasaponins I–III were iso- of Z . jujuba fruit extract and green tea extract lated from the fresh leaves of Zizyphus jujuba , produced an enhanced cell growth inhibition compound 2 and 3 exhibited antisweet activity effect, and that the resultant G1 arrest was caused (Yoshikawa et al. 1991 ) . via a different mechanism as that of CHCl(3)-F treatment alone (Huang et al. 2008a ) . Further studies showed that the CHCl(3)-F and green tea Anticancer Activity extract enhanced anticancer activity by reducing the expression of APRIL (a proliferation-induc- Jujube seed oil at 0.35 or 1.40 mL/kg could prolong ing ligand), which was expressed in HepG2 cells life-span over 50% and inhibit increase of body (Huang et al. 2009 ) . The scientists speculated Ziziphus jujuba 589 that the CHCl(3)-F and green tea extract mixture membrane during metastasis, where MMP-2 had might provide a lead to a new drug design to treat been implicated in the development and dissemi- hepatocellular carcinoma in the future. Z. jujuba nation of malignancies. The medicinal herb- aqueous extract showed inhibitory effects against mediated inhibition of endothelial MMP may human tumour cell lines, HEp-2, HeLa and Jurkat boost a therapeutic ef fi cacy during vascular leukemic cell lines (Vahedi et al. 2008 ) . Jurkat angiogenesis. leukemic line was the most sensitive cells with

IC50 of 0.1 m g/mL. This cell line also displayed a typical DNA laddering. The crude methanolic Antiin fl ammatory Activity extract of Zizyphus jujuba was highly cytotoxic (73.33%) at the concentration of 1,000 (m g/mL) Ethanolic jujube fruit extract signi fi cantly inhib- while the rest of the test fractions were low in ited carrageenan-induced paw oedema and cotton toxicity at the same concentration (Ahmad et al. pellet-induced granuloma pouch (Shah et al. 2011 ) . 1989a ) . Pharmacological studies demonstrated Deproteinized polysaccharide isolated from that the compound prescription Huangqin Tang Z. jujuba was found to compose of two fractions and its component drugs: roots of Paeonia with average molecular weights of 143,108 and lacti fl ora, Scutellaria baicalensis and Glycyrrhiza 67,633 Da (Hung et al. 2012 ) . The 3-(4,5-dimeth- uralensis, and the fruit of Ziziphus jujuba showed ylthiazol-2-yl)-2,5-diphenyltetrazolium bromide marked anti in fl ammatory effect (Huang et al. test showed that the antiproliferation effect of the 1990) . The compound prescription and its com- deproteinized polysaccharide on melanoma cells ponent drugs, except the peony root, also pos- followed a dose- and time-dependent course with sessed signifi cant antispastic effect. Studies

IC50 values of 3.99 mg/mL after 24-h treatment showed that the % inhibition of paw oedema at but decreased signifi cantly to 3.36 mg/mL after 3 h after carrageenan administration produced by 48 h. The cell cycle assay revealed melanoma Z. jujuba leaf extracts at 200, 400 and 600 mg/kg cells to be arrested in G2/M phase. Moreover, was 44.5, 62.2 and 81.8%, respectively, com- with the deproteinized polysaccharide treatment, pared to the control (Kumar et al. 2004 ) . The paw the apoptotic bodies were generated, accompa- oedema attenuating effect of Z. jujuba leaf nied by an increase in caspase-3 and caspase-9 extracts at the dose of 600 mg/kg was comparable activity. The results suggested that the depro- with that produced by diclofenac sodium (88.6%). teinized polysaccharide may be used as a potential The results showed that Ziziphus jujuba leaf anti-skin cancer agent. extracts possessed signi fi cant antiin fl ammatory activity against carrageenan-induced rat paw oedema. Z. jujuba leaf extract was found to possess Antiangiogenic Activity signifi cant antiinfl ammatory activity against carrageenan-induced rat paw edema in rats The medicinal herb of Aspergillus usamii var. (Shiv et al. 2004 ) . shirousamii -transformed Angelicae gigantis Bioactivity-guided fractionation of petro- Radix and Zizyphus jujuba (tAgR and tZj) was leum ether- and EtOAc-soluble extracts of the found to have antiangiogenic activity (Kang et al. seeds of Ziziphus jujuba using a cyclooxyge- 2009 ) . The medicinal herb signi fi cantly sup- nase-2 assay as a monitor indicated that the pressed phorbol 12-myristate 13-acetate (PMA)- triglyceride, 1,3-di-O -[9(Z)-octadecenoyl]-2- induced matrix metalloproteinases MMP-2 O -[9(Z),12(Z)-octadecadienoyl]glycerol (3), production and prevented vascular endothelial and a fatty acid mixture of linoleic, oleic and growth factor-stimulated endothelial cell trans- stearic acids, were the major active components migration and tube formation. Invasive cancer (Su et al. 2002 ) . A new pentacyclic lupane-type cells had been reported to utilize MMP to degrade triterpene derivative, 3- O -[9(Z)-octadecenoyl] the extracellular matrix and vascular basement betulinic acid (1), and betulinic acid (2) were 590 Rhamnaceae also isolated and identifi ed. All isolates as well Antiulcerogenic Activity as pure linoleic, oleic and stearic acids were evaluated for their inhibitory effects against In the pylorus ligation-induced ulcer model, both cyclooxygenases-1 (COX-1) and -2 (COX- Ziziphus jujuba leaf extract pretreatment in rats 2). Cox inhibitors have antiinfl ammatory prop- caused signifi cant reduction in gastric volume, erties. This study was undertaken to evaluate free acidity, total acidity and ulcer index com- the effect of essential oil from seeds of Zizyphus pared to the control group (Ganachari and Kumar jujuba on TPA(12-O -tetradecanoylphorbol-13- 2004a ) . In ethanol-induced ulcers, the extract acetate)-induced skin infl ammation model in was effective in reducing lesion index and increas- mice, treatment with 1 and 10% of essential oil ing the gastric mucus content. It was also effec- of Z. jujuba seeds caused signi fi cant decrease tive in decreasing ulcer index in aspirin-induced in ear thicknesses and reduced respectively. ulcers. All the results obtained with the extract Further, histological analysis clearly confi rmed were dose dependent. All the results suggested that Z. jujuba essential oil inhibited the that Ziziphus jujuba leaf extract possessed infl ammatory responses of skin infl ammation in signifi cant and dose-dependent antiulcer activity. mice. The antiulcer activity of the extract could be Pretreament of Wistar albino rats with attributed to its cytoprotective and antisecretory Ziziphus jujuba fruit hydroalcoholic extract action. elicited marked dose-dependent attenuation in paw edema compared to control (Goyal et al. 2011 ) . The extract signi fi cantly decreased gran- Antiobesity and uloma tissue formation caused by interscapular Antihypercholesterolemic Activities implantation of sterile cotton pellets compared to control. The extract also decreased the ele- Studies found that Z. jujuba seeds at 64 mg/kg/ vated serum nitrite/nitrate level caused by day administered intra-peritoneally for 20 days chronic infl ammation. The extract was found to could reduce the levels of total cholesterol and contain jujubosides, fl avonoids and terpenes, LDL-cholesterol, increase HDL-cholesterol which may produce the marked anti- and HDL 2 -cholesterol of rats fed on normal infl ammatory effect of jujube fruit in acute and diet (Yuan and Li 1990 ) . The extract at the chronic in fl ammation, possibly by inhibiting same dosage could reduce triglycerides, and nitric oxide expression. The results suggested increase HDL2-cholesterol of rats fed on rich- the potential for the therapeutic use of Z. jujuba fat diet. fruit as an anti-infl ammatory agent. Among six The hydroalcoholic extract of Ziziphus jujuba fractions extracted from Z. jujube , fraction F leaves at the doses of 200, 400 and 600 mg/kg, (triterpene acids fraction) was demonstrated to p.o. given daily to sucrose induced- obese rats for be the most active part in inhibitory effects the 125 days caused reduction in body weight, daily infl ammatory cells activated by Euphorbia kan- food intake and serum total cholesterol, LDL- sui and prostratin, a phorbol ester isolated from cholesterol, VLDL-cholesterol and triglycerides Euphorbia fi scheriana (Yu et al. 2012 ) . Of 21 along with an increase in HDL-cholesterol levels compounds isolated from Z. jujube, 7 com- (Ganachari and Kumar 2004b ) . The results pounds were found to have pronounced inhibi- obtained with 400 and 600 mg/kg dose of Ziziphus tory action on the activated infl ammatory cells. jujuba extract were signi fi cant when compared to The scientist asserted that these compounds may sucrose control group. These results suggested be helpful in attenuating the irritant action of that Ziziphus jujuba leaf extract possessed Euphorbiaceae plants and protect the gastroin- signifi cant weight reducing, hypophagic and testinal tissue from potent infl ammatory injury, hypolipidemic properties in sucrose-induced and would be benefi cial to some diseases, like obese rats. In a recent study, treatment with an in fl ammatory bowel disease. extract of Z. jujuba suppressed lipid accumulation Ziziphus jujuba 591 and glycerol-3-phosphate dehydrogenase (GPDH) Antiamnesic Activity activity without affecting cell viability (Kubota et al. 2009 ) . Further fractionation of the initial Z . Among 50 Korean traditional plants tested, the jujuba extract with organic solvent revealed that methanolic extracts from Zizyphus jujuba showed the chloroform fraction (CHCl(3)-F) elicited the the highest activation effect (34.1%) on choline most inhibitory effect, which involved signifi cant acetyltransferase in vitro (Heo et al. 2003 ) . By attenuation of the expression of key adipogenic sequential fractionation of Zizyphus jujuba , the transcription factors, including peroxisome pro- active component was fi nally identifi ed as cis -9- liferator-activated receptor (PPAR) g and CCAAT octadecenoamide (oleamide). After isolation, enhancer binding proteins (C/EBPs) at the protein oleamide showed a 65% activation effect. level. The results suggested that the chloroform Administration of oleamide (0.32%) to mice fraction may block adipogenesis, at least in part, signifi cantly reversed the scopolamine-induced by decreasing the expression of PPARgamma, C/ memory and/or cognitive impairment in the pas- EBP a and b . sive avoidance test and Y-maze test. Injection of scopolamine to mice impaired performance on the passive avoidance test (31% decrease in step- Effect on Chronic Constipation through latency), and on the Y-maze test (16% decrease in alternation behavior). In contrast, Z. jujuba extract was found to be an effective and mice treated with oleamide before scopolamine safe treatment for chronic constipation (Naftali injection were protected from these changes et al. 2008 ) . Clinical studies showed that patients (12–25% decrease in step-through latency; with a prolonged transit time (TT), taking the 1–10% decrease in alternation behavior). These extract had their TT decreased from 12.2 particles results suggested that oleamide should be a use- to 3 particles at week 11. Symptom severity rat- ful chemo-preventive agent against Alzheimer’s ings decreased from 6 and 6.2 to 2 and 5, and the disease. quality of life score improved from 1.9 and 2.3 to 1.3 and 1.4 in the extract and control groups, respectively. Anticonvulsant Activity A water-soluble carbohydrate concentrate (WSCC) prepared from Chinese jujube contained The hydroalcoholic extract of Zizyphus jujuba carbohydrates (771 g/kg of WSCC) including (HEZJ) fruit (1,000 mg/kg) exhibited maximum glucose, fructose, pectin polysaccharide, and protection (100%) against generalized tonic-clonic hemicelluloses (Huang et al. 2008b ) . The admin- seizures in the pentylenetetrazole (PTZ) seizure istration of WSCC (5.0 and 15 g/ kg of diet) model and 66.7% protection against tonic hindlimb effectively shortened gastrointestinal transit time, extension in the maximal electroshock (MES) sei- reduced caecal ammonia, elevated total short- zure model (Pahuja et al. 2011 ) . Signi fi cant impair- chain fatty acid concentrations in caecum (3-4- ment in cognitive functions was observed in both fold), increased faecal moisture, reduced daily PTZ- and MES-challenged rats. Pretreatment with faecal ammonia output and decreased the activi- the extract resulted in signifi cant improvement in ties of b-D-glucuronidase (by 73.0–73.8%), b -D- learning and memory. The extract also reversed glucosidase (by 58.2–85.7%), mucinase (by the oxidative stress induced by both PTZ and 46.2–72.6%), and urease (by 31.9–48.7%) in MES. The signi fi cant decrease in cholinesterase faeces. This study suggested that adequate con- activity observed in the PTZ and MES models was sumption of jujube WSCC (at least 5.0 g/kg of signi fi cantly reversed by pretreatment with the diet or 40 mg/day) might exert favourable effects extract. The results demonstrated the anticonvul- on improving the gastrointestinal milieu and sant effect of jujube fruit extract as well as amelio- reduce the exposure of intestinal mucosa to toxic ration of cognitive impairment induced by seizures ammonia and other detrimental compounds. in rats. 592 Rhamnaceae

Anxiolytic/Sedative Activity excitatory signal pathway in hippocampus and probably acted through its anti-calmodulin A C-glycosyl fl avane named spinosin (2“- O- b - action. glucosylswertisin) and its acylated derivatives The ethanolic extract of Ziziphus jujuba seed isolated from the seeds were found to possess (SZJE) orally administered to male ICR mice at mild sedative activity (Woo et al. 1979 ) . Swertisin the dosage 0.5–2.0 g/kg increased the fi rst time was also found in small quantity. Three acylated entry, total changes and times spent in the white fl avone-C-glycosides, (namely 6‴-sinapoyls- chamber of the black and white test (BWT) (Peng pinosin, 6‴-feruloylspinosin and 6‴-p -couma- et al. 2000 ) . The SZJE at the dosage 0.5–1.0 g/kg roylspinosin) were identifi ed from Z. jujuba seeds increased the percentage of time-spent and the (Woo et al. 1980 ) . All showed mild sedative percentage of arm entries in the open arms of the activity in pharmacological tests. The seeds and elevated plus maze (EPM) and decreased the per- leaves of jujube exerted a similar inhibiting effect centage of time-spent and the percentage of arm on central nervous system function, while the entries in the closed arms of the EPM. fruits was synergistic with pentobarbitol sodium Furthermore, the SZJE at the dosage of 1. 0 g/kg and thiopental sodium on prolongation of sleep prolonged the hexobarbital-induced sleeping and sedation, and also decreased coordinated time in mice and decreased the locomotor activ- action (Wu et al. 1993 ) . Jujuboside A exerted no ity in rats. These results suggested that SZJE pos- inhibiting effect, but was synergistic with pheny- sessed anxiolytic effect at lower dose and sedative lalanine on central nervous system function. effect at higher dose. The fl avonoid isolated from Jujuboside A, an effective component of sanzao- Z. jujuba seeds, spinosin and swertish were found ren (Z. jujuba seed), a Chinese herbal medicine, to possess signi fi cant sedative activity (Cheng was found to be a non-competitive inhibitor of et al. 2000) . Studies showed that Jujuboside A calmodulin (Zhou et al. 1994 ) . Calmodulin is a administered intracerebroventricular in urethane- primary Ca2 + -binding protein found in all anaesthetized rats signifi cantly decreased the eukaryotic cells (Zhang and Yuan 1998 ) . It cou- slopes of excitatory postsynaptic potential (EPSP) ples the intracellular Ca2+ signal to many essen- and the amplitudes of population spike (PS) in tial cellular events by binding and regulating the the fi rst responses of granule cells and signi fi cantly activities of more than 40 different proteins decreased EPSP and PS in the responses of CA1 and enzymes in a Ca2 + -dependent manner. pyramidal cells (Shou et al. 2002). There was Jujuboside inhibition of calmodulin was thought good correlation between in-vivo and in-vitro to be linked to its sedative properties (Zhou et al. results. Jujuboside A is a main component of 1994 ) . In another study, a high dose of Jujuboside jujubogenin extracted from the seed of Ziziphus A inhibited the hyperactivity of rat hippocampal jujuba var spinosa which is widely used in CA1 neurons induced by penicillin sodium (Shou Chinese traditional medicine for the treatment of et al. 2001 ) . Further research showed that penicil- insomnia and anxiety, a Chinese herbal medicine, lin increased the hippocampal glutamate concen- has long been known as a sedative-hypnotic tration and a high dose of Jujuboside A (0.1 g/L) drug. signi fi cantly blocked penicillin-induced gluta- Saponins from Ziziphus jujuba seeds exhibited mate release (Zhang et al. 2003 ) . It was found sedative and hypnotic effect (Jiang et al. 2007a ) . that glutamate (0.5 mM) induced an intracellular Saponins are thought to be the main bioactive fac- [Ca2+ ] increase and Jujuboside A signi fi cantly tors in Chinese traditional medicine for the treat- inhibited the glutamate-induced Ca2+ increase. ment of anxiety and insomnia because of its effect The calmodulin (CaM) antagonist trifl uoperazine of decreasing monoaminergic system activity. (TFP) showed a similar inhibitory effect as Animal studies conducted to investigate sedative Jujuboside A. These observations suggested that and hypnotic effects of jujube saponins showed JuA had inhibitory effects on glutamate-mediated that two saponin compounds from Z. jujuba seeds Ziziphus jujuba 593 exerted a signi fi cant effect on walking time kaloid-A, daechualkaloid-C (lyscimine), daechual- compared with that of the control group (Jiang kaloid-E (nornuciferine), daechucyclopeptide-I, et al. 2007a ) . Compound I had a signifi cant effect and zizyphusine. Twelve cyclopeptide alkaloids on coordinated movement. Both compounds from Daechu stem-bark: daechuine-S1 (frangufo- prolonged the suprathreshold barbiturate induced line), daechuine- S2, (frangulanine), daechuine-S4 sleeping time. The number of sleeping animals (franganine), daechuine-S5, daechuine-S3, increased by 30 and 20% for compounds I and II, daechuine-S6, daechuine-S7, daechuine-S8-1, respectively, under the subthreshold dose daechuine –S9 (mucronin-D), daechuine-S10, of sodium barbital. In further animal studies daechuine-S26, daechuine-S27 (Nummularin-B). fl avonoids and saponins from Z. jujuba seeds Oral administration of the methanol extract (1 g/ caused a signi fi cant reduction of walking time and kg) of sanjoin fruit in mice prolonged the hexo- coordinated movement ability of mouse, and barbital sleeping time by >67% compared to the signifi cantly prolonged its sleeping time at 40 mg/ control group. The butanol fraction of the extract kg, ip, subthreshold dose and increased the sleep- showed more potent sedative activity. Sanjoine-A ing number of animals at 50 mg /kg, ip, super- and nuciferine showed strong sedative activity threshold dose induced by coeliac injection of whereas zizyphusine and + coclaurine did not. sodium barbital (Jiang et al. 2007b) . Comparative It was highly probable that some of the sedative analysis showed that saponins had a more effec- activity of the butanol fraction may be attributable tive sedative and hypnotic function than that of to the minor alkaloids. fl avonoids while polysaccharides did not show Sanjoinine-A (frangufoline) was bound to any sedative and hypnotic effect. Calmodulin protein at two sets of binding sites Sedative principles of the seeds of Zizyphus in the calcium ion-dependent manner in rat brain vulgaris var. spinosus were characterized as cytoplasm (Han et al. 1993 ) . The inhibitory sanjoinine-A (frangufoline), nuciferine and their activity of the various cyclopeptides and peptide congeners (Han and Park 1987a ) . Heat treatment alkaloids from Zizyphus species on Ca2+ -ATPase of sanjoinine-A produced a more active artifact was found to correlate well with their sedative sanjoinine-Ahl. Sedative activity of Zizyphi fruc- activity (Hwang et al. 2001 ) . Calmodulin- tus was determined by potentiation of hexobarbital- induced activation of Ca2+ -ATPase was strongly induced hypnosis test and its active principles inhibited by sanjoinine-A dialdehyde (IC50 , were characterized as nornuciferine and lysi- 2.3 m M), -Ah1 (IC50 , 4.0 m M), -A (IC50 , 4.6 m M), camine (Han and Park 1987b ) . A new cyclopep- and -G2 (IC50 , 7.2 m M), while calmodulin- tide alkaloid, daechucyclopeptide-1 was isolated induced activation of phosphodiesterase was together with zizyphusine. Sedative alkaloids in strongly inhibited by both deachuine S10 (IC50 , two varieties of Z. jujuba were extensively studied 4.9 mM) and sanjoinine-D (IC50 , 9.0 m M). The by Han et al. (1989b ) in Korea. Alkaloids found sedative peptide alkaloids from Zizyphus spe- in the seeds of Z. vulgaris var. spinosus (Sanjoin) cies inhibited calmodulin-dependent protein include: sanjoinine-A, sanjoinine-B, sanjoinine- kinase II (Han et al. 2005 ) . All 13 alkaloids D, sanjoinine-F, sanjoinine-G1 and sanjoinenine tested were stronger inhibitors than chlorprom- cyclopeptide alkaloids and sanjoinine-G2 as open azine (IC50 , 98 m M) on calmodulin-dependent chain peptide alkaloid. Other sanjoinine alkaloids protein kinase II. Among them, the most potent were identifi ed as sanjoinine-E (nuciferine), inhibitor was daechuine S27 (IC50 2.95 m M), sanjoinine-Ia (nornuciferine), sanjoinine-Ib (nori- which was stronger than pimozide (IC50 socorydine), N-methylasimolobin, caaverine 15.0 m M). A study of fi ve men and ten women which are aporphine alkaloids. sanjoinine-K was suffering general malaise showed that adminis- identifi ed a + coclaurine, a benzylisoquinoline alka- tration of jujube extract had a sedative and adap- loid. Zizyphusine was identi fi ed as a quaternary togenic effect (Goetz 2009 ) aporphine alkaloid. Alkaloids found in the fruit of Studies showed that the water extract of daechu, Z. jujuba var. inermis included daechual- Suanzaoren (jujube seed, SWE) (400 and 800 mg/ 594 Rhamnaceae kg body wt.) and the ether extract of Danshen and tolbutamide. The minimum lethal dose was (DTT) (300 and 600 mg/kg body wt.) decreased greater than 3,000 mg/kg, orally in mice. In sleep latency signi fi cantly, increased sleeping alloxan diabetic rats both methanol extracts of time and prolonged movement convalescence Zizyphus spina christi (ZSC) and Zizyphus jujuba time induced by sodium pentobarbital (55 mg/kg (ZJ) roots signi fi cantly reduced fasting serum glu- body wt.) administration in mice (Fang et al cose level and markedly increased serum insulin 2010 ) . Further, the combination of SWE and level (Said et al. 2006 ) . ZJ signi fi cantly reduced DTT showed signi fi cant synergistic effect in serum total lipids (TL), triglycerides (TG), total decreasing sleep latency and increasing sleeping cholesterol (TC) and lipid peroxides (LP), low time, but not in prolonging the movement conva- density lipoprotein cholesterol (LDL-C), but no lescence time, which might be helpful for energy signi fi cant difference on high density lipoprotein recovery in the treatment of insomnia. The results cholesterol (HDL-C). Meanwhile, ZSC caused a suggested that SWE, DTT, and their combination noticeable decrease in TC, TG and LP compared possessed signi fi cant sedative-hypnotic activity, with the untreated diabetic rats. ZJ signifi cantly which supported the popular use of Suanzaoren decreased alanine transaminase (ALT), aspartate and Danshen for treatment of insomnia. transaminase (AST) and total bilirubin (TB) in These results of studies suggested that the diabetic rats. Serum creatinine and urea showed hypnotic effect of jujubosides on normal rats may signifi cant reduction in diabetic rats treated with be infl uenced by circadian rhythm and the sero- ZSC extract. Both extracts produced no tonergic system may be involved in the hypnotic signifi cant changes in all studied parameters effect of jujubosides (Cao et al. 2010 ) . During except for a signifi cant reduction of serum lipid daytime (9:00–15:00), jujubosides signifi cantly peroxides and urea by ZJ extract as compared to increased the total sleep and rapid eye movement untreated diabetic control. The data revealed (REM) sleep without signi fi cant in fl uence on that both extracts of ZSC and ZJ had benefi cial non-REM (NREM) sleep. During nighttime effects on diabetic rats. They reduced hyperg- (21:00–3:00), jujubosides signifi cantly increased lycemia, hyperlipidemia and lipid peroxides total sleep and NREM sleep especially the light associated with diabetes. Besides, they were sleep and showed no signifi cant effect on REM safe towards liver and kidney functions. The sleep and slow wave sleep (SWS). In pentobarbital- effect of Z. jujube roots was more pronounced treated mice, jujubosides signifi cantly augmented than that of Zizyphus spina Christi roots. In a the hypnotic effect of pentobarbital evidenced by recent study, hydro-alcoholic extract of Z. jujuba increasing sleep time and this augmentative effect leaves was found to have hypoglycaemic effect was potentiated by 5-hydroxytryptophan. Further, in alloxan- induced diabetic rats (Shirdel et al. jujubosides inhibited the para-chlorophenylala- 2009 ) . In diabetic rats treated with the extract, nine-induced suppression of pentobarbital- signi fi cant reduction of glucose–triglyceride-cho- induced hypnosis. lesterol, LDL and VLDL levels resulted. Z. jujuba also increased HDL levels signi fi cantly. Both studies con fi rmed fi ndings of earlier studies con- Hypoglycaemic Activity ducted by Iganacimuthu and Amalraj ( 1998 ) on alloxan-induced diabetic rats. Adminstration of single (100–400 mg/kg) oral doses of jujube alcoholic leaf extract to normal rats showed a dose-dependent statistically Antiatherosclerotic Activity signifi cant lowering of blood glucose 2, 4 and 6 h later (Anand et al. 1989 ) . The effect was most Crude Z. jujuba fruit and seed extracts signifi cantly pronounced at 6 h with blood glucose returning to inhibited the foam cell formation induced by control values at 24 h. In alloxan-diabetic rats, no acetylated low density lipoprotein (Fujiwara et al. signi fi cant effect was observed with the extract 2011) .Further thery found that triterpenoids such Ziziphus jujuba 595 as oleanonic acid, pomolic acid, and pomonic hydroxynonenal, an indicator of lipid peroxidation, acid were the major active compounds, and triter- were much lower than those in the vehicle-treated penoids containing a carboxylic acid at C-28 ischemia group after ischemia/reperfusion. The played an important role in the inhibitory effect results suggested that the repeated supplements of on foam cell formation in human macrophages. jujube could protect neurons from ischemic dam- Their data suggest that triterpenoids in Zizyphus age via up-regulation of SOD1 and reduction of jujuba fruits and seeds, may therefore be useful lipid peroxidation in the ischemic hippocampal for the prevention of atherosclerosis. CA1 region. Hwang et al. (2011 ) found that admin- istration of Z. jujuba methanol extract signifi cantly increased the number of Ki67 (a marker for cell Antiplatelet Activity proliferation)-positive cells in the subgranular zone of the dentate gyrus of middle-aged mice. Further, A neo-lignan isolated from Z. jujuba leaves was the extract signifi cantly increased doublecortin found to increase the release of endogenous pros- (a marker for neuroblast differentiation)-immuno- taglandin I2 from the rat aorta by up to 25.3% at reactive neuroblasts with tertiary dendrites, but not 3 mg/mL (Fukuyama et al. 1986 ) . Prostaglandin those without tertiary dendrites, in the dentate I2 or prostacyclin had been reported to be both a gyrus. Also, doublecortin protein levels in the potent inhibitor of platelet aggregation and a extract-treated groups tended to increase dose- powerful vasodilator (Kelton and Blajchman dependently. The results suggested that the repeated 1980 ) . It may play an important role in limiting supplement of Z. jujuba methanol extract may platelet-mediated thrombosis. increase the hippocampal plasticity in middle-aged mice.

Neuroprotective and Central Nervous System Activity Analgesic and Antipyretic Activities

Methanol extract of seeds of Zizyphus jujuba var. Ethanolic jujube fruit extract exhibited signi fi cant spinosa , at a concentration range of 0.05–5 analgesic activity (Shah et al. 1989a ) . Jujube fruit m g/mL, inhibited N-methyl-D-aspartate (NMDA) extract also exhibited antipyretic activity, it did (1 mM)-induced neuronal cell death in cultured not produce any signi fi cant effect on body tem- rat cerebellar granule neuron (Park et al. 2004 ) . perature and isolated guinea pig tracheal chain The extract (0.5 m g/mL) inhibited glutamate release (Shah et al. 1989a ) . Pharmacological studies into medium induced by NMDA (1 mM). demonstrated that the compound prescription Pretreatment of the extract (0.5 m g/mL) inhibited Huangqin Tang and its component drugs, roots of NMDA (1 mM)-induced elevation of cytosolic cal- Paeonia lacti fl ora, Scutellaria baicalensis and cium concentration. In another study, jujube fruit Glycyrrhiza uralensis, and the fruit of Ziziphus extract exerted neuroprotective effects against isch- jujuba exhibited antipyretic, analgesic and seda- emic damage in gerbil hippocampus after repeated tive effects (Huang et al. 1990 ). oral supplementation (Yoo et al. 2010 ) . The treat- ment signi fi cantly decreased the reactive gliosis of astrocytes and microglia in the CA1 region com- Antispasmodic Activity pared to that in the vehicle-treated group. Immunoreactivities of Cu,Zn-superoxide dismutase Studies demonstrated that the compound pre- (SOD1) and brain-derived neurotrophic factor in scription Huangqin Tang and its component the jujube-treated ischemia group were higher drugs, Scutellaria baicalensis and Glycyrrhiza those in the vehicle-treated ischemia group 4 days uralensis , and the fruit of Ziziphus jujuba except after ischemia/reperfusion. In addition, in the the peony root also possessed signi fi cant anti- jujube-treated ischemia group, levels of spasmodic activity (Huang et al. 1990 ). 596 Rhamnaceae

Antimicrobial Activity Antifertility Activity

Ethanolic jujube fruit extract inhibited the growth Ethyl acetate extract of Zizyphus jujuba bark of Bacillus subtilis (Shah et al. 1989a) . Active arrested the normal estrus cycle of adult female principles in jujube fruit inhibited insoluble mouse at diestrus stage and reduced the wet glucan formation by the cariogenic bacterium, weight of ovaries signi fi cantly (Gupta et al. Streptococcus mutans (Kohda et al. 1986 ) . 2004 ) . Cholesterol and ascorbic acid content in Hydrodistilled volatile oil from the seeds of ovaries of crude extract-treated mice were Zizyphus jujuba exhibited strong detrimental signi fi cantly elevated. The signi fi cant inhibition effect against all fi ve strains of Listeria monocy- of d (5)-3b -hydroxysteroid dehydrogenase (d (5)- togenes (Al-Reza et al. 2009 ) The oil also had 3 b -HSD) and glucose-6-phosphate dehydroge- potent antioxidant activity. Using 2,2-diphenyl- nase (G-6-PDH), the two key enzymes involved

1-picrylhydrazyl (DPPH) assay, the IC50 value of in ovarian steroidogenisis, were also observed in the Z. jujuba essential oil was determined to be mouse after 18 days of treatment. Normal oestrus 5.21 mg/mL. Among the extracts, the strongest cycle and ovarian steroidogenisis were restored activity was exhibited by the methanol extract after withdrawal of treatment with the bark extract with an IC 50 value of 20.44 m g/mL. In the super- on average 32 days. Antifertility activities of oxide radicals scavenging activities assay, meth- crude bark extracts were found to be reversible. anol extract was superior to all other extracts

(IC50 = 18.60 m g/mL). The results indicated that the essential oil and extracts of Z. jujuba could Hepatoprotective Activity serve as natural antimicrobial and antioxidant agents for the food industry. Low activity was Methanolic extract of Zizyphus jujuba fruits was shown by the crude methanolic extract (12%) of found to possess hepatoprotective activity prob- Z. jujuba, n-hexane (9%), chloroform (20%) and ably due to its antioxidant effect (Kumar et al. ethyl acetate (14%) fraction against Penicillium 2009 ) . The low and medium doses of the extract notatum (Ahmad et al. 2011 ) . Low activity signi fi cantly inhibited the acute elevation of was shown by the n-hexane fraction against biomarkers in serum and elevated the fall of Aspergillus niger (10%) and Trichoderma har- biomarkers in the rat liver tissue homogenate zianum (13%) and inactive against Aspergillus with paracetamol and thioacetamide induced fl avus, Fusarium oxysporum and Rhizopus stolo- hepatic damage. The activities of antioxidants nifer. The chloroform fraction exhibited low enzymes were signifi cantly increased in liver tis- activity of 10% against F. oxysporum while sue homogenate of rats pretreated with low and showing no activity against the rest of the test medium doses of the extract. Results of histo- fungi. All the test samples were inactive against pathological studies supported the biochemical Rhizopus stolonifer. fi ndings. However, high dose of the extract was less effective than low and medium doses.

Hypotensive and Antinephritic Activity Cardioprotective and Cerebral-Protective Kim and Han ( 1996 ) found that Ziziphus jujuba Activity stimulated nitric oxide release in-vitro, in cul- tured endothelial cells and in-vivo, in the kidney The increases of lactate dehydrogenase release tissues of rats. They suggested that Z. jujuba may from damaged myocardial cells induced by depri- possess hypotensive (reduction of blood pressure) vation of oxygen and glucose or treatment with and antinephritic (reduction of in fl ammation of chlorpromazine and mitomycin C were attenuated the kidney) action, possibly by increasing renal by Z. jujuba seed (33 m g/mL) except 11 m g/mL blood fl ow. which showed no effect on mitomycin C (24 h) Ziziphus jujuba 597 and chlorpromazine (9 h)-induced injuries (Chen water-soluble polysaccharides in Chinese jujube et al. 1990 ) . These data suggested that Z. jujuba leaves, fruits and fl owers (Zhao et al. 2008 ) . All seed could be an effective protective drug for the extracts were very rich in sugars such as uronic myocardial cells. Studies showed that Z. jujuba acid, arabinose and galactose. Polymers extracted seed possessed protective effects on cerebral isch- with hot water from different pant parts were emic injuries (Bai et al. 1996 ) . Total saponins of different in the degree of branching and degree of seeds of Chinese jujube reduced the contents of esterifi cation. All water-soluble polysaccharides water and malondialdehyde in ischemic rat’s brain exhibited immunobiological activities especially tissues, elevated the activity of superoxide dis- from the fruits and fl owers. Separate studies mutase, creatine kinase and lactate dehydroge- showed that the crude extract of polysaccharide nase, decreased the content of lactate and allevi- from Z. jujuba cv. Jinsixiaozao, a major Chinese ated the damages of nerve cells in the brain. cultivar, to have potential anti-complementary activity (Li et al. 2011b ) . The polysaccharide extract dramatically increased thymus and spleen Antidiarrhoeal Activity indices in mice and enhanced proliferation of splenocytes and peritoneal macrophages. In an ethnobotanical survey of antidiarrhoeal plants Immunobiological tests indicated that two frac- of Parinche valley, Pune district, Maharashtra, India, tions, coded ZSP3c and ZSP4b, were the main Z. jujuba was identi fi ed as one of the 28 plants with active components. ZSP3c was rich in pectin with antidiarrhoeal activity (Tetali et al. 2009 ) . a degree of esterifi cation (DE) of 49%, which may be related to its stronger immunological activity. Among 11 triterpenoides isolated from the fruit, Permeability Enhancing Activity compounds 3-O - cis - p -coumaroyl maslinic acid (5), 3-O - trans - p -coumaroyl maslinic acid (6), and To assess the permeability enhancing activity of oleanolic acid (8), exhibited signi fi cant anticomple-

Ziziphus jujuba, an aqueous extract of seeds was mentary activity with IC50 values of 101.4, 143.9, compared to two members of a known series of and 163.4 mM, respectively, whereas the cean- permeability enhancement agents belonging to the othane-type and the lupane-type triterpenes were alkylglycosides (Elery and Dovlatabadi 2001 ) . inactive (Lee et al. 2004b ). This suggested that the The Z. jujuba extract lowered cell monolayer resis- oleanane-structure played an important role in tance more rapidly in a given time period than the inhibiting the haemolytic activity of human serum alkylglycosides and allowed full recovery of cells against erythrocytes. in a relatively short time period. The extract of Z. jujuba appeared to be more ef fi cient as a permea- bility enhancer than the two alkylglycosides. Antiallergic Activity

Jujubosides A1 and C and acetyljujuboside B Immunobiological/Anticomplementary isolated from Zizyphus jujuba var. spinosa seeds Activity were found to inhibit the histamine release from rat peritoneal exudate cells induced by antigen- Protojujubosides A and jujubosides A, B, and C antibody-reaction (Yoshikawa et al. 1997 ) . isolated from Zizyphus jujuba var. spinosa seeds were found to show potent immunological adju- vant activity (Matsuda et al. 1999 ) . Z. jujuba Antigenotxic Activity hydroalcoholic leaf extract at 5–50 m g/mL was found to stimulate in-vitro chemotactic, phago- Animal studies showed that Z. jujuba and cytic and intracellular killing potency of human Origanum majorana extracts exhibited protection neutrophils (Ganachari et al. 2004 ) . Pectic against hydroquinone-induced clastogenetic polysaccharides were the major components in all effects and histological changes when treated 598 Rhamnaceae alone or combination with hydroquinone important adjunctive herb to other tonics, especially (Ghaly et al. 2008 ) . Z. jujuba extract was in combination with ginseng (Tang Kue) in China more effective than O. majorana extract. and Korea. Chinese jujube is universally believed Hydroquinone is a myelotoxin that is found in in the Asia to build strength, remove obstruction to many foods and formed through the metabo- energy fl ow, Qi and enhance longevity. The fruits lism of benzene. The scientists concluded both are widely used in Chinese and Korean traditional extracts to be useful especially for people who medicine, where they are believed to alleviate are occupationally exposed to benzene or its stress, for the treatment of various diseases such as metabolites. chronic fatigue, loss of appetite, diarrhoea, anae- mia, pain, cough, irritability, hysteria pharyngitis, bronchitis, anorexia, dysosmia, chalelithiasis, sed- Hair Promoting Activity ative, corn of foot. The fruits are also believed to possess activities such as anodyne, anticancer, Z. jujuba essential oil was found to possess hair refrigerant, sedative, antifungal, antibacterial, anti- growth promoting activity (Yoon et al. 2010 ) . After ulcer, antiin fl ammatory, antispasmodic, sedative, 21 days, mice treated with 1 and 10% of oil pro- antifertility, hypotensive, antinephritic, stomachic, duced a greater effect on the length of hair which antiallergic, pectoral, expectorant, styptic, laxative, were measured to be 9.96 and 10.02 mm, respec- and tonic. In India, the fruit is believed to purify tively, as compared to the control (8.94 mm). Based the blood and to aid in digestion. In China, the on the weight of hair/cm2 area of dorsal skin, hair seeds are used traditionally for insomnia, irrita- thickness and hair follicles, it was found the best bility, neurasthermia, physical emaciation, and as results was for 1% of essential oil treated mice. a remedy for diarrhoea. The leaves are an ingredient used by some Benue tribes in prescription for gonorrhea. The Toxicity Studies pounded leaves are applied as a dressing to wounds. The leaves, in plaster form are used in Ethanolic jujube fruit extract was found to be strangury. A paste made from the tender leaves devoid of any signifi cant toxic effects as evalu- and twigs is applied to boils, abscesses, and car- ated by acute toxicity test observations made for buncles to promote suppuration. In the Philippines, 24 h and chronic treatment of animals for a decoction of the bark and leaves has been 3 months (Shah et al. 1989a ) . During acute toxic- employed as an effective astringent in dysentery ity, test observations were made for 24 h while and diarrhea and is used in bowel trouble of all the animals were treated for 3 months in chronic kinds. treatment. No signi fi cant changes in external The bark has been used for diarrhoea in India, morphological changes, visceral toxicity, haema- as a tonic for digestion in Java and as a tonic for tological changes, spermatogenic dysfunction, digestion in Malaysia. besides effects on average body weight and vital The root has some purgative effect, and is said to organ weight were recorded. be drastic if taken in excess. In Angola, it is taken to promote menstruation. A root decoction is used for fevers. In India, the powdered root is applied to Traditional Medicinal Uses ulcers and wounds. The juice of the root bark is used as a purgative, and, externally, in gout and rheuma- Various parts of the tree are used in traditional med- tism. The bark is bitter and is sometimes used for icine for a variety of diseases and disorders in many colic; it is probably emetic in larger doses. It is also Asian countries ( Burkill 1966 ; CSIR 1976 ; Zeng used for tanning in India. The bark in powdered et al. 1987; Natural Products Research Institute form, or in decoction, is astringent and a simple rem- 1998 ; Azam-Ali et al. 2006 ; Mahajan and Chopda edy for diarrhoea. The powdered bark is a domestic 2009 ) . Chinese jujube has been used since ancient dressing for old wounds and ulcers. In Cambodia, times as a nutrient tonic, a blood cleanser, and as an the bark is prescribed in dysentery and gingivitis. Ziziphus jujuba 599

Al-Reza SM, Bajpai VK, Kang SC (2009) Antioxidant Other Uses and antilisterial effect of seed essential oil and organic extracts from Zizyphus jujuba . Food Chem Toxicol 47(9):2374–2380 In India, jujube is also grown as a host plant for the Al-Reza SM, Yoon JI, Kim HJ, Kim JS, Kang SC lac insect, Laccifer lacca. The wood is durable and (2010) Anti-in fl ammatory activity of seed essential hard, used in turnery and suitable for wood fl oor, oil from Zizyphus jujuba. Food Chem Toxicol 48(2):639–643 furniture and construction. In Korea the wood to Anand KK, Singh B, Chand D, Chandan BK, Gupta VN make the body of the taepyeongso , a double-reed (1989) Effect of Zizyphus sativa leaves on blood wind instrument and for making Go bowls. In glucose levels in normal and alloxan-diabetic rats. Bhutan, the leaves are used as a potpourri to help J Ethnopharmacol 27(1–2):121–127 Azam-Ali S, Bonkoungou E, Bowe C, deKock C, Godara keep the houses of the inhabitants smelling fresh A, Williams JT (2006) Ber and other jujubes. and clean. It is also said to keep bugs and other International Centre for Underutilised Crops, insects out of the house and free of infestation. In Southampton, 289 pp the traditional Chinese wedding ceremony, jujube Bai X, Huang Z, Mo Z, Pan H, Ding H (1996) Effects of total saponins of semen Ziziphi Spinosae on brain and walnut were often placed in the newlyweds’ damages and brain biochemical parameters under bedroom as a sign of fertility. The fragrance of the cerebral ischemia of rats. Zhongguo Zhong Yao Za fl owers are said to make teenagers fall in love, Zhi 21(2):110–112 (In Chinese) consequently young men will take a fl owering Bai YJ, Cheng G, Tao J, Wang B, Zhao YY, Liu Y, Ma LB, Tu GZ (2003) Structure identi fi cation of jujuboside E. shoot and put it on their hats to woo the opposite Yao Xue Xue Bao 38(12):934–937 (In Chinese) sex in the Himalaya and Karakoram regions. In Burkill IH (1966) A Dictionary of the Economic Products Japan, the natsume has given its name to a style of of the Malay Peninsula. Revised reprint. 2 volumes. tea caddy used in the Japanese tea ceremony. In Ministry of Agriculture and Co-operatives, Kuala Lumpur, Malaysia. Vol 1 (A-H) pp 1–1240, vol 2 (I-Z). Abyssinia, the fruit is used to stupefy fi sh. pp 1241–2444 The crude methanolic extract of Zizyphus Cacig S, Radu F, Lupea AX, Ifrim I (2006) Analysis of jujuba showed signi fi cant antitermite activity fl avonoids in Hydrangea paniculata and Ziziphus against Heterotermes indicola , among the test jujuba extracts using fl ash chromatography and HPLC. Rev Chim 57(12):1197–1201 samples (Ahmad et al. 2011 ) . All the test samples Cao JX, Zhang QY, Cui SY, Cui XY, Zhang J, Zhang YH, except n-hexane showed low activity (20%) against Bai YJ, Zhao YY (2010) Hypnotic effect of jujubo- Tribolium castaneum . The n-hexane fraction sides from Semen Ziziphi Spinosae. J Ethnopharmacol showed low activity (20%) against Rhizopertha 130(1):163–166 Chang SC, Hsu BY, Chen BH (2010) Structural character- dominica while the rest of the fractions were inac- ization of polysaccharides from Zizyphus jujuba and tive against it. Low activity of 40 and 20% was evaluation of antioxidant activity. Int J Biol Macromol shown by the chloroform and n-hexane fraction 47(4):445–453 respectively against Callosbruchus analis . Chen Y, Schirarend C (2007) Rhamnaceae. In: Wu ZY, Raven PH, Hong DY (eds) Flora of China, vol 12, Hippocastanaceae through Theaceae. Science Press/ Missouri Botanical Garden Press, Beijing/St. Louis Comments Chen XJ, Yu CL, Liu JF (1990) Protective effects of total saponins of Semen Ziziphi Spinosae on cultured rat myocardial cells. Zhongguo Yao Li Xue Bao Kirkbride et al. ( 2006 ) proposed the name 11(2):153–155 (In Chinese) Ziziphus jujuba as the correct scientifi c name Cheng G, Bai YJ, Zhao YY, Tao J, Lin Y, Tu GZ, Ma LB, of the species for conservation against the para- Liao N, Xu XJ (2000) Flavonoids from Ziziphus jujuba tautonym Ziziphus zizyphus (L.) H. Karsten. Mill var. spinosa . Tetrahedron 56(45):8915–8920 Choi SH, Ahn JB, Kozukue N, Levin CE, Friedman M (2011) Distribution of free amino acids, fl avonoids, total phenolics, and antioxidative activities of jujube Selected References (Ziziphus jujuba) fruits and seeds harvested from plants grown in Korea. J Agric Food Chem Ahmad B, Khan I, Bashir S, Azam S, Ali N (2011) The 59(12):6594–6604 antifungal, cytotoxic, antitermite and insecticidal Council of Scientifi c and Industrial Research (CSIR) activities of Zizyphus jujuba. Pak J Pharm Sci (1976) The wealth of India. A dictionary of Indian 24(4):489–493 raw materials and industrial products (Raw materials 600 Rhamnaceae

11). Publications and Information Directorate, New Guo S, Duan JA, Tang YP, Yang NY, Qian DW, Su SL, Delhi Shang EX (2010a) Characterization of triterpenic Cyong JC, Takahashi M (1982) Identifi cation of guanos- acids in fruits of Ziziphus species by HPLC-ELSD-MS. ine 3¢ :5 ¢ -monophosphate in the fruit of Zizyphus J Agric Food Chem 58(10):6285–6289 jujube . Phytochemistry 21(8):1871–1874 Guo S, Duan JA, Tang YP, Zhu ZH, Qian YF, Yang NY, Elery JG, Dovlatabadi H (2001) Permeability enhancement Shang EX, Qian DW (2010b) Characterization of activity from Ziziphus jujuba. Pharmaceut Biol nucleosides and nucleobases in fruits of Ziziphus 40(2):149–153 jujuba by UPLC-DAD-MS. J Agric Food Chem Fang XS, Hao JF, Zhou HY, Zhu LX, Wang JH, Song FQ 58(19):10774–10780 (2010) Pharmacological studies on the sedative-hyp- Guo S, Duan JA, Tang Y, Qian D, Zhu Z, Qian Y, Shang notic effect of Semen Ziziphi spinosae (Suanzaoren) E, Su S (2011a) UHPLC-TOFMS coupled with and Radix et Rhizoma Salviae miltiorrhizae (Danshen) chemometric method as a powerful technique for extracts and the synergistic effect of their combina- rapid exploring of differentiating components tions. Phytomedicine 17(1):75–80 between two Ziziphus species. J Sep Sci Foundation for Revitalisation of Local Health Traditions 34(6):659–666 (2008) FRLHT Database. htttp://envis.frlht.org Guo S, Duan JA, Tang Y, Qian Y, Zhao J, Qian D, Su S, Fujiwara Y, Hayashida A, Tsurushima K, Nagai R, Shang E (2011b) Simultaneous qualitative and quanti- Yoshitomi M, Daiguji N, Sakashita N, Takeya M, tative analysis of triterpenic acids, saponins and Tsukamoto S, Ikeda T (2011) Triterpenoids isolated fl avonoids in the leaves of two Ziziphus species by from Zizyphus jujuba inhibit foam cell formation in HPLC-PDA-MS/ELSD. J Pharm Biomed Anal macrophages. J Agric Food Chem 59(9):4544–4552 56(2):264–270 Fukuyama Y, Mizuta K, Nakagawa K, Chin WJ, Wa XE Gupta M, Mazumder UK, Vamsi ML, Sivakumar T, (1986) A new neo-lignan, a prostaglandin I2 inducer Kandar CC (2004) Anti-steroidogenic activity of the from the leaves of Ziziphus jujuba . Planta Med two Indian medicinal plants in mice. J Ethnopharmacol 6:501–502 90(1):21–25 Ganachari MS, Kumar S (2004a) Anti-ulcer properties of Han BH, Park MH (1987a) Alkaloids are the sedative Ziziphus jujuba Lam leaves extract in rats. J Nat Rem principles of the seeds of Zizyphus vulgaris var. spino- 4(2):103–108 sus . Arch Pharm Res 10(4):203–207 Ganachari MS, Kumar S (2004b) Effect of Ziziphus jujuba Han BH, Park MH (1987b) Sedative activity and its active leaf extract on body weight, food intake and serum components of Zizyphi fructus. Arch Pharm Res lipid levels in sucrose-induced obese rats. Indian 10(4):208–211 J Pharmaceut Sci 68(3):363–365 Han BH, Park MH, Wah ST (1987) Structure of daechual- Ganachari MS, Shiv K, Bhat KG (2004) Effect of Ziziphus kaloid-A, a new pyrrolidine alkaloid of novel skeleton jujube leaves extract on phagocytosis by human neu- from Ziziphus jujuba var. inermis . Tetrahedron Lett trophils. J Nat Rem 4(1):47–51 28(34):3957–3958 Ghaly IS, Said A, Abdel-Wahhab MA (2008) Zizyphus Han BH, Park MH, Han YN (1989a) Aporphine and tetra- jujuba and Origanum majorana extracts protect hydrobenzylisoquinoline alkaloids from the seeds of against hydroquinone-induced clastogenicity. Environ Zizyphus vulgaris var. spinosus . Arch Pharm Res Toxicol Pharmacol 25(1):10–19 12(4):263–268 Goetz P (2009) Demonstration of the psychotropic effect Han BH, Park MH, Park JH (1989b) Chemical and phar- of mother tincture of Zizyphus jujuba Mill. macological studies on sedative cyclopeptide alkaloids Phytotherapie 7(1):31–36 (In French) in some Rhamnaceae plants. Pure Appl Chem Goyal R, Sharma PL, Singh M (2011) Possible attenua- 61:443–448 tion of nitric oxide expression in anti-in fl ammatory Han BH, Park MH, Han YN (1990) Cyclic peptide and effect of Ziziphus jujuba in rat. J Nat Med peptide alkaloids from seeds of Ziziphus vulgaris . 65(3–4):514–518 Phytochemistry 29(10):3315–3319 Guil-Guerrero JL, Delgado AD, González MCM, Isasa Han YN, Kim GY, Hwang KH, Han BH (1993) Binding MET (2004) Fatty acids and carotenes in some ber of sanjoinine-A (frangufoline) to calmodulin. Arch ( Ziziphus jujuba Mill) varieties. Plant Foods Hum Pharm Res 16(4):289–294 Nutr 59(1):23–27 Han YN, Hwang KH, Han BH (2005) Inhibition of calm- Guo S, Duan JA, Tang Y, Su S, Shang E, Ni S, Qian D odulin-dependent protein kinase II by cyclic and linear (2009a) High-performance liquid chromatography– peptide alkaloids from Zizyphus species. Arch Pharm two wavelength detection of triterpenoid acids from Res 28(2):156–163 the fruits of Ziziphus jujuba containing various culti- Heo HJ, Park YJ, Suh YM, Choi SJ, Kim MJ, Cho HY, vars in different regions and classi fi cation using Chang YJ, Hong B, Kim HK, Kim E, Kim CJ, Kim chemometric analysis. J Pharm Biomed Anal BG, Shin DH (2003) Effects of oleamide on choline 49(5):1296–1302 acetyltransferase and cognitive activities. Biosci Guo S, Tang YP, Duan JA, Su SL, Ding AW (2009b) Two Biotechnol Biochem 67(6):1284–1291 new terpenoids from fruits of Ziziphus jujuba . Chin Hu SY (2005) Food plants of China. The Chinese Chem Lett 20(2):197–200 University Press, Hong Kong, 844 pp Ziziphus jujuba 601

Huang L, Ye W, Cai B, Li D, Liu J, Liu M (1990) A pre- Gigantis Radix and Zizyphus jujuba . Nutr Res Pract liminary study on the pharmacology of the compound 3(1):3–8 prescription Huangqin Tang and its component drugs. Kawai KI, Akiyama T, Ogihara Y, Shibata S (1974) A new Zhongguo Zhong Yao Za Zhi 15(2):115–117 (In sapogenin in the saponins of Zizyphus jujuba, Hovenia Chinese) dulcis and Bacopa monniera . Phytochemistry Huang X, Kojima-Yuasa A, Norikura T, Kennedy DO, 13(12):2829–2832 Hasuma T, Matsui-Yuasa I (2007) Mechanism of the Kelton JG, Blajchman MA (1980) Prostaglandin I2 anti-cancer activity of Zizyphus jujuba in Hep G2 (prostacyclin). Can Med Assoc J 122(2):175–179 cells. Am J Chin Med 35:517–523 Kennedy LM, Halpern BP (1980) Extraction, Huang X, Kojima-Yuasa A, Xu S, Norikura T, Kennedy puri fi cation and characterization of a sweetness DO, Hasuma T, Matsui-Yuasa I (2008a) Green tea modifying component from Ziziphus jujuba. Chem extract enhances the selective cytotoxic activity of Senses 5:123–147 Zizyphus jujuba extracts in HepG2 cells. Am J Chin Kim HY, Han SW (1996) Zizyphus jujuba and Codonopsis Med 36(4):729–744 pilosula stimulate nitric oxide release in cultured Huang YL, Yen GC, Sheu F, Chau CF (2008b) Effects of endothelial cells and kidney tissues. Asia Pac water-soluble carbohydrate concentrate from Chinese J Pharmacol 11(3–4):121–128 jujube on different intestinal and fecal indices. J Agric Kirkbride JH Jr, Wiersema JH, Turland NJ (2006) Proposal Food Chem 56(5):1734–1739 to conserve the name Ziziphus jujuba against Z. zizy- Huang X, Kojima-Yuasa A, Xu S, Kennedy DO, Hasuma phus (Rhamnaceae). Taxon 55:1049–1050 T, Matsui-Yuasa I (2009) Combination of Zizyphus Kohda H, Kozai K, Nadgasaka N, Miyako Y, Suginaka H, jujuba and green tea extracts exerts excellent cytotoxic Hidaka K, Yamasaki K (1986) Prevention of dental activity in HepG2 cells via reducing the expression of caries by oriental folk medicines – active principles of APRIL. Am J Chin Med 37(1):169–179 Ziziphi Fructus for inhibition of insoluble glucan Hudina M, Liu M, Veberic R, Stampar F, Colaric M (2008) formation by cariogenic bacterium, Streptococcus Phenolic compounds in the fruit of different varieties mutans . Planta Med 2:119–120 of Chinese jujube (Ziziphus jujuba Mill ). J Hort Sci Kubota H, Morii R, Kojima-Yuasa A, Huang X, Yano Y, Biotechnol 83(3):305–308 Matsui-Yuasa I (2009) Effect of Zizyphus jujuba Hung CF, Hsu BY, Chang SC, Chen BH (2012) extract on the inhibition of adipogenesis in 3 T3-L1 Antiproliferation of melanoma cells by polysaccharide preadipocytes. Am J Chin Med 37(3):597–608 isolated from Zizyphus jujuba. Nutrition 28(1):98–105 Kumar S, Ganachari MS, Banappa NVS (2004) Anti- Hwang KH, Han YN, Han BH (2001) Inhibition of calm- in fl ammatory activity of Ziziphus jujuba Lam leaves odulin-dependent calcium-ATPase and phosphodi- extract in rats. J Nat Rem 4(2):183–185 esterase by various cyclopeptides and peptide alkaloids Kumar SP, Asdaq SB, Kumar NP, Asad M, Khajuria D from the Zizyphus species. Arch Pharm Res (2009) Protective effect of Zizyphus jujuba fruit extract 24(3):202–206 against paracetamol and thioacetamide induced Hwang IK, Yoo KY, Yoo DY, Choi JH, Lee CH, Kang IJ, hepatic damage in rats. Internet J Pharmacol 7(1) Kwon DY, Kim YS, Kim DW, Won MH (2011) Kundu AB, Barik BR, Mondal DN, Dey AK, Banerji A Zizyphus enhances cell proliferation and neuroblast (1989) Zizyberanalic acid, a pentacyclic triterpenoid differentiation in the subgranular zone of the dentate of Zizyphus jujuba . Phytochemistry 28(11):3155–3158 gyrus in middle-aged mice. J Med Food Kurihara Y (1992) Characteristics of antisweet substances, 14(3):195–200 sweet proteins, and sweetness-inducing proteins. Crit Iganacimuthu S, Amalraj T (1998) Effect of leaf extract of Rev Food Sci Nutr 32(3):231–252 Zizyphus jujuba on diabetic rats. Indian J Pharmacol Kurihara Y, Ookubo K, Tasaki H, Kodama H, Akiyama Y, 30:107–112 Yagi A, Halpern B (1988) Studies on the taste Ikram M, Ogihara Y, Yamasaki K (1981) Structure of new modi fi ers. I. Puri fi cation and structure determination saponin from Zizyphus vulgaris . J Nat Prod of sweetness inhibiting substance in leaves of Ziziphus 44(1):91–93 jujuba. Tetrahedron 44(1):61–66 Jiang JG, Huang XJ, Chen J (2007a) Separation and Lee SS, Lin BF, Liu KC (1996) Three triterpene esters purifi cation of saponins from semen Ziziphus jujuba from Zizyphus jujuba . Phytochemistry 43(4):847–851 and their sedative and hypnotic effects. J Pharm Lee SM, Min BS, Lee CG, Kim KS, Kho YH (2003) Pharmacol 59(8):1175–1180 Cytotoxic triterpenoids from the fruits of Zizyphus Jiang JG, Huang XJ, Chen J, Lin QS (2007b) Comparison jujuba . Planta Med 69(11):1051–1054 of the sedative and hypnotic effects of fl avonoids, Lee SM, Park JK, Lee CG (2004a) Quantitative determi- saponins, and polysaccharides extracted from Semen nation of triterpenoids from the fruits of Ziziphus Ziziphus jujuba . Nat Prod Res 21(4):310–320 jujuba . Nat Prod Sci Korea 10(3):93–95 Kang SW, Choi JS, Bae JY, Li J, Kim DS, Kim JL, Shin Lee SM, Park JG, Lee YH, Lee CG, Min BS, Kim JH, Lee SY, You HJ, Park HS, Ji GE, Kang YH (2009) HK (2004b) Anti-complementary activity of triterpe- Blockade of vascular angiogenesis by Aspergillus noides from fruits of Zizyphus jujuba. Biol Pharm Bull usamii var. shirousami i-transformed Angelicae 27:1883–1892 602 Rhamnaceae

Li JW, Ding SD, Ding XL (2005a) Comparison of antioxi- Outlaw WH Jr, Zhang S, Riddle KA, Womble AK, dant capacities of extracts from fi ve cultivars of Anderson LC, Outlaw WM, Outlaw NN, Outlaw EC, Chinese jujube. Process Biochem 40(11):3607–3613 Thistle AB (2002) The jujube (Ziziphus jujuba Mill.), Li LM, Liao X, Peng AL, Ding LS (2005b) Chemical a multipurpose plant. Econ Bot 56(2):198–200 Constituents from the Seeds of Ziziphus jujuba var Pahuja M, Mehla J, Reeta KH, Joshi S, Gupta YK (2011) spinosa (Bunge) Hu. J Integr Plant Biol 47(4): Hydroalcoholic extract of Zizyphus jujuba ameliorates 494–498 seizures, oxidative stress, and cognitive impairment in Li J, Shan L, Liu Y, Fan L, Ai L (2011a) Screening of a experimental models of epilepsy in rats. Epilepsy functional polysaccharide from Zizyphus jujuba cv. Behav 21(4):356–363 Jinsixiaozao and its property. Int J Biol Macromol Pandey MB, Singh AK, Singh JP, Singh VP, Pandey VB 49(3):255–259 (2008a) Three new cyclopeptide alkaloids from Li JW, Fan LP, Ding SD (2011b) Isolation, purifi cation Zizyphus species. J Asian Nat Prod Res and structure of a new water-soluble polysaccharide 10(7–8):719–723 from Zizyphus jujuba cv. Jinsixiaozao. Carbohydr Pandey MB, Singh AK, Singh VP, Pandey VB (2008b) Polym 63(2):477–482 Cyclopeptide alkaloids from Zizyphus sativa bark. Nat Liberty Hyde Bailey Hortorium (1976) Hortus third. A Prod Res 22(3):219–221 concise dictionary of plants cultivated in the United Park JH, Lee HJ, Koh SB, Ban JY, Seong YH (2004) States and Canada. Liberty Hyde Bailey Hortorium/ Protection of NMDA-induced neuronal cell damage Cornell University/Wiley, New York, 1312 pp by methanol extract of Zizyphi spinosi semen in cul- Liu MJ, Cheng CY (1995) A taxonomic study on the tured rat cerebellar granule cells. J Ethnopharmacol genus Ziziphus . Acta Hort 390:161–166 95(1):39–45 Liu QX, Wang B, Liang H, Zhao YY, Liu MJ (2004) Pawlowska AM, Camangi F, A B (2009) Flavonoids of Structure identifi cation of jujuboside D. Yao Xue Xue Zizyphus jujuba L. and Zizyphus spina-christi (L.) Willd Bao 39(8):601–604 (In Chinese) (Rhamnaceae) fruits. Food Chem 112(4):858–862 Mahajan RT, Chopda MZ (2009) Phyto-pharmacology of Peng WH, Hsieh MT, Lee YS, Lin YC, Liao J (2000) Ziziphus jujuba Mill – a plant review. Pharmacog Rev Anxiolytic effect of seed of Ziziphus jujuba in mouse 3:320–329 models of anxiety. J Ethnopharmacol 72(3): Malik A, Kuliev ZA, Akhmedov YA, Vdovin AD, 435–441 Abdullaev ND (1997) Proanthocyanidins of Ziziphus Porcher MH et al (1995–2020) Searchable world wide jujuba . Chem Nat Comp 33(2):165–173 web multilingual multiscript plant name database. Malik A, Kuliev ZA, Akhmedov UA, Vdovin AD, Abdullaev Published by The University of Melbourne. Australia. ND (2002) New oligomeric proanthocyanidine from http://www.plantnames.unimelb.edu.au/Sorting/ Ziziphus jujuba . Chem Nat Comp 38(1):40–42 Frontpage.html Matsuda H, Murakami T, Ikebata A, Yamahara J, Reich L (1991) Uncommon fruits worthy of attention. Yoshikawa M (1999) Bioactive saponins and glyco- Addison-Wesley, Reading, pp 139–146 sides. XIV. Structure elucidation and immunological Said AA, El-Sayed EM, Hussein HM (2006) adjuvant activity of novel protojujubogenin type triter- Antihyperglycemic, antihyperlipidemic and antioxidant pene bisdesmosides, protojujubosides A, B, and B1, effects of Zizyphus spina christi and Zizyphus jujuba in from the seeds of Zizyphus jujuba var. spinosa (Zizyphi alloxan diabetic rats. Int J Pharmacol 2(5):563–570 Spinosi Semen). Chem Pharm Bull(Tokyo) 47(12): Shah AH, Pandey VB, Eckhardt G, Tschesche R (1984a) 1744–1748 Sativanine-C: a cyclopeptide alkaloid from the bark of Mukhtar HM, Ansari SH, Ali M, Naved T (2004) New Ziziphus sativa . Phytochemistry 23(4):931–933 compounds from Zizyphus vulgaris . Arch Physiol Shah AH, Pandey VB, Singh JP, Singh KN, Eckhardt G Biochem 42(7):508–511 (1984b) Sativanine-G, a cyclopeptide alkaloid from Naftali T, Feingelernt H, Lesin Y, Rauchwarger A, Ziziphus sativa . Phytochemistry 23(9):2120–2121 Konikoff FM (2008) Ziziphus jujuba extract for the Shah AH, Pandey VB, Eckhardt G, Tschesche R (1985a) treatment of chronic idiopathic constipation: a con- A 13- membered cyclopeptide alkaloid from Ziziphus trolled clinical trial. Digestion 78:224–228 sativa . Phytochemistry 24(11):2765–2767 Natural Products Research Institute (1998) Medicinal Shah AH, Pandey VB, Eckhardt G, Tschesche R (1985b) plants in the Republic of Korea . Western paci fi c series An Nformyl cyclopeptide alkaloid from the bark of no 21. Seoul National University, WHO Regional Ziziphus sativa . Phytochemistry 24(11):2768–2770 Publications, Gwanak , 316 pp Shah AH, Pandey VB, Eckhardt G, Tschesche R (1985c) Niu JW, Zhang QW, Gong MX, Yan LH, Zhu JJ, Wang Sativanine-E, a new 13- membered cyclopeptide alka- ZM, Li QF (2008) Determination of zizybeoside II of loid containing a short side chain, from Ziziphus Ziziphus jujuba by HPLC. Zhongguo Zhong Yao Za sativa . J Nat Prod 48(4):555–558 Zhi 33(24):2935–2937 (In Chinese) Shah AH, Miana GA, Devi S, Pandey VB (1986) Otsuka H, Akiyama T, Kawai K, Shibata S, Inoue O, Sativanine-H: a new alkaloid from the bark of Ziziphus Ogihara Y (1978) The structure of jujubosides A and sativa . Planta Med 6:500–501 B, the saponins isolated from the seeds of Zizyphus Shah AH, Al-Yahya MA, Devi S, Pandey VB (1987) jujube . Phytochemistry 17(8):1349–1352 Sativanine-K: an additional N-formyl cyclopeptide Ziziphus jujuba 603

alkaloid from Ziziphus sativa . Phytochemistry 26(4): Tschesche R, Shah AH, Eckhardt G (1979) Sativanine-A 1230–1232 and sativanine-B, two new cyclopeptide alkaloids Shah AH, Ai-Bekairi AM, Qureshi S, Ageel AM (1989a) from the bark of Ziziphus sativa . Phytochemistry Ziziphus jujuba fruits: evaluation of some biological 18(4):702–704 activities and toxicity. Phytother Res 3(6):232–236 Uphof JCT (1968) Dictionary of economic plants, 2nd Shah AH, Al-Yahya MA, El-Sayed AM, Tariq M, Ageel AM edn. (1st edn. 1959). Cramer, Lehre, 591 pp (1989b) Cyclopeptide alkaloids: further studies on mau- U.S. Department of Agriculture, Agricultural Research ritine-C and sativanine-C. Pak J Pharm Sci 2(2):81–89 Service (USDA) (2012) USDA National nutrien data- Shibata S, Nagai Y, Tanaka O, Doi O (1970) A sapogenin base for standard reference, Release 25. Nutrient Data of seeds of Zizyphus jujuba var. spinosus . Laboratory Home Page. http://www.ars.usda.gov/ba/ Phytochemistry 9(3):677 bhnrc/ndl Shirdel Z, Madani H, Mirbadalzadeh R (2009) Vahedi F, Najafi MF, Bozari K (2008) Evaluation of inhib- Investigation into the hypoglycemic effect of hydroal- itory effect and apoptosis induction of Zyzyphus jujuba coholic extract of Ziziphus jujuba leaves on blood glu- on tumor cell lines, an in vitro preliminary study. cose and lipids in alloxan- induced diabetes in rats. Cytotechnology 56(2):105–111 Iran J Diabetes Lipid Disord 8(2):13–19 Vidrih R, Ulrih NP, Zlatić E, Hribar J, Prgomet Z (2008) Shiv K, Ganachari MS, Banappa Nagoor VS (2004) Anti- The nutritional and physico-chemical properties of infl ammatory activity of Ziziphus jujuba Lamk. leaves ripe (Ziziphus jujuba ) fruits grown in Istria. Acta Hort extract in rats. J Nat Rem 4:183–185 (ISHS) 840:525–528 Shou CH, Wang J, Zheng XX, Guo DW (2001) Inhibitory Wang W, Chen WW (1991) Antioxidative activity studies effect of jujuboside A on penicillin sodium induced on the meaning of same original of herbal drug and hyperactivity in rat hippocampal CA1 area in vitro. food. Zhong Xi Yi Jie He Za Zhi 11(3):159–161 Acta Pharmacol Sin 22(11):986–990 (In Chinese) Shou CH, Feng Z, Wang J, Zheng XX (2002) The inhibi- Wang JZ, Yang JS (2008) Structural elucidation of triter- tory effects of jujuboside A on rat hippocampus in vivo pene saponins from the seeds of Zizyphus jujuba Mill. and in vitro. Planta Med 68(9):799–803 Chin J Org Chem 28(1):69–72 Singh S, Pandey MB, Singh JP, Pandey VB (2006) Peptide Wang QL, Yuan BX, Huang JH, Gao W, Gao QM, Liu AF alkaloids from Zizyphus sativa bark. J Asian Nat Prod (1995) Effects of oil of Ziziphus spinosus Hu on life- Res 8(8):733–737 span and body weight of mice suffering from Ehrlich Smith VV, Halpern BP (1983) Selective suppression of ascites cancer. J Xi’an Med Univ 16(3):295–297 judged sweetness by ziziphins. Physiol Behav Wang SM, Bi ZM, Li P, Ye WC, Yi L (2005) A new angu- 30(6):867–874 lar furano fl avonol rhamnoside from seeds of Ziziphus Su BN, Cuendet M, Farnsworth NR, Fong HH, Pezzuto JM, jujuba var. s pinosa (Bunge) Hu. Chem Ind Forest Prod Kinghorn AD (2002) Activity-guided fractionation of 25(1):37 the seeds of Ziziphus jujuba using a cyclooxygenase-2 Wong KC, Chee SG, Tan CH (1996) Volatile constituents inhibitory assay. Planta Med 68(12):1125–1128 of the fruit of Ziziphus jujuba Mill. var. inermis . Sun YF, Liang ZS, Shan CJ, Viernstein H, Unger F (2011) J Essent Oil Res 8(3):323–326 Comprehensive evaluation of natural antioxidants and Woo WS, Kang SS, Shim SH, Wagner H, Chari VM, antioxidant potentials in Ziziphus jujuba Mill. var. Seligmann O, Obermeier G (1979) The structure of spinosa (Bunge) Hu ex H.F. Chou fruits based on geo- spinosin (2″-O -beta-glucosylswertisin) from Ziziphus graphical origin by TOPSIS method. Food Chem vulgaris var. spinosus . Phytochemistry 18(2):353–355 124(4):1612–1619 Woo WS, Kang SS, Wagner H, Seligmann O, Chari VM Tetali P, Waghchaure C, Daswani PG, Antia NH, Birdi (1980) Acylated fl avone-C-glycosides from the seeds of TJ (2009) Ethnobotanical survey of antidiarrhoeal Zizyphus jujuba. Phytochemistry 19(12):2791–2793 plants of Parinche valley, Pune district, Maharashtra, Wu S, Zhang JB, Jhao S, Li M, Lan M (1989) Effects of India. J Ethnopharmacol 123(2):229–236 Ziziphus spinosa Hu on serum lipoprotein and experi- Thakur RS, Jain MP, Hruban L, Santavý F (1975) mental atherosclerosis. Zhongguo Zhong Yao Za Zhi Terephthalic acid and its methyl esters from Zizyphus 14(7):50–57 (In Chinese) sativa . Planta Med 28(2):172–173 Wu SX, Zhang JX, Xu T, Li LF, Zhao SY, Lan MY (1993) Tomoda M, Shimuju N, Gonda R (1985) Pectic sub- Effects of seeds, leaves and fruits of Ziziphus spinosa stances. II. The location of O - acetyl groups and the and jujuboside A on central nervous system function. Smith degradation of Ziziphus jujuba Pectin A. Chem Zhongguo Zhong Yao Za Zhi 18:685–687 (In Chinese) Pharm Bull 33(9):4017–4020 Xue ZP, Feng WH, Cao JK, Cao DD, Jiang WB (2009) Tripathi M, Pandey MB, Jha RN, Pandey VB, Tripathi Antioxidant activity and total phenolic contents in peel PN, Singh JP (2001) Cyclopeptide alkaloids from and pulp of Chinese jujube ( Ziziphus jujuba Mill) Zizyphus jujuba . Fitoterapia 72(5):507–510 fruits. J Food Biochem 33(5):613–629 Tschesche R, Khokhar I, Wilhelm H, Eckhardt G (1976) Yamada H, Imoto T (1987) Inhibitory effect of the extract Jubanin A and jubanin-B, new cyclopeptide alkaloids from Zizyphus jujuba leaves on sweet taste responses from Ziziphus jujuba. Phytochemistry 15(4): of the chorda tympani in the rat and hamster. Comp 541–542 Biochem Physiol A Comp Physiol 88(2):355–360 604 Rhamnaceae

Yoo KY, Li H, Hwang IK, Choi JH, Lee CH, Kwon DY, Zhang M, Ning G, Shou C, Lu Y, Hong D, Zheng X (2003) Ryu SY, Kim YS, Kang IJ, Shin HC, Won MH (2010) Inhibitory effect of jujuboside A on glutamate-medi- Zizyphus attenuates ischemic damage in the gerbil hip- ated excitatory signal pathway in hippocampus. Planta pocampus via its antioxidant effect. J Med Food Med 69(8):692–695 13(3):557–563 Zhang M, Zhang Y, Xie J (2008) Simultaneous determina- Yoon JI, Al-Reza SM, Kang SC (2010) Hair growth pro- tion of jujuboside A, B and betulinic acid in semen moting effect of Zizyphus jujuba essential oil. Food Ziziphi spinosae by high performance liquid chroma- Chem Toxicol 48(5):1350–1354 tography-evaporative light scattering detection. J Yoshikawa K, Shimono N, Arihara S (1991) Antisweet Pharm Biomed Anal 48(5):1467–1470 substances, jujubasaponins I–III from Zizyphus jujuba Zhang H, Jiang L, Ye S, Ye Y, Ren F (2010) Systematic revised structure of ziziphin. Tetra Lett 32(48): evaluation of antioxidant capacities of the ethanolic 7059–7062 extract of different tissues of jujube (Ziziphus jujuba Yoshikawa M, Murakami T, Ikebata A, Wakao S, Murakami Mill.) from China. Food Chem Toxicol 48(6): N, Matsuda H, Yamahara J (1997) Bioactive saponins 1461–1465 and glycosides. X. On the constituents of zizyphi spinosi Zhao J, Li SP, Yang FQ, Li P, Wang YT (2006) semen, the seeds of Zizyphus jujuba Mill. var. spinosa Simultaneous determination of saponins and fatty Hu (1): structures and histamine release-inhibitory acids in Ziziphus jujuba (Suanzaoren) by high perfor- effect of jujubosides A1 and C and acetyljujuboside B. mance liquid chromatography-evaporative light scat- Chem Pharm Bull(Tokyo) 45(7):1186–1192 tering detection and pressurized liquid extraction. J Yu L, Jiang BP, Luo D, Shen XC, Guo S, Duan JA, Tang YP Chromatogr A 1108(2):188–194 (2012) Bioactive components in the fruits of Ziziphus Zhao ZH, Liu MJ, Tu PF (2008) Characterization of water jujuba Mill. against the in fl ammatory irritant action of soluble polysaccharides from organs of Chinese Jujube Euphorbia plants. Phytomedicine 19(3–4):239–244 (Ziziphus jujuba Mill. cv. Dongzao). Eur Food Res Yuan BX, Li Q (1990) Effects of saponnins of Zizyphus Technol 226(5):985–989 jujuba Mill. seeds (ZS) on plasma lipids and lipoprotein- Zhou Y, Li Y, Wang Z, Ou Y, Zhou X (1994) 1 H NMR cholesterins of rats. Chin Pharmacol Bull 6(1):34–36 and spin-labeled EPR studies on the interaction of Zeng L, Zhang RY, Wang X (1987) Studies on the con- calmodulin with jujuboside A. Biochem Biophys Res stituents of Zizyphus spinosus Hu. Yao Xue Xue Bao Commun 202(1):148–154 22(2):114–120 (In Chinese) Ziyaev R, Irgashev T, Israilov IA, Abdullaev ND, Yunusov Zhang M, Yuan T (1998) Molecular mechanisms of calm- MS, Yunusov SY (1977) Alkaloids of Ziziphus jujuba odulin’s functional versatility. Biochem Cell Biol the structure of juziphine and juzirine. Chem Nat 76(2–3):313–323 Comp 13(2):204–207 本文献由“学霸图书馆-文献云下载”收集自网络，仅供学习交流使用。

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