The Pharma Innovation Journal 2018; 7(9): 330-336

ISSN (E): 2277- 7695 ISSN (P): 2349-8242 NAAS Rating: 5.03 Sanbhaloo ( negundo): Pharmacological Actions TPI 2018; 7(9): 330-336 © 2018 TPI and Therapeutic Benefits: A Review www.thepharmajournal.com Received: 08-07-2018 Accepted: 10-08-2018 Shamim, Saad Ahmed and Lubna Fatima

Shamim Research Associate (Unani), Abstract Central Council for Research in Sanbhaloo (Vitex negundo) is a drug of herbal origin. The word vitex is derived from the latin ‘vieo’ Unani Medicine, Ministry of (meaning to tie or bind) because of the flexible nature of its stems and twigs. It is a woody, aromatic AYUSH, Govt. of deciduous growing to a small tree. Vitex negundo is also known as the five-leafed chaste tree or monk’s pepper. Its most striking feature centers on a cluster of five pointed leaves resembling a palm. Saad Ahmed The drug has effectively been employed for the treatment of waja-ul-mafasil (arthritis), warm-e-

Consultant (Unani), Central khussiyatain (orchitis), warm-e-reham (cervicitis), warm-e-miqad (proctitis), warm-e-tihal, bawaseer Council for Research in Unani (haemorrhoids), warm-e-shobetein (bronchitis), zeequnnafs (asthma) etc. In this paper, an effort has been Medicine, Ministry of AYUSH, made to review and compile the Pharmacological Actions and Therapeutic Benefits Sanbhaloo (Vitex Govt. of India negundo). Lubna Fatima Consultant (Unani), Central Keywords: Sanbhaloo, Vitex negundo, Unani Medicine, Traditional Medicine Council for Research in Unani Medicine, Ministry of AYUSH, 1. Introduction Govt. of India Sanbhaloo (Vitex negundo) is a drug of herbal origin. The word vitex is derived from the latin

‘vieo’ (meaning to tie or bind) because of the flexible nature of its stems and twigs. Of the 270 known species of the genus, about18 are in cultivation and are referred to as chaste tree, or simply Vitex. The genus was established by Linnaeus in 1753 with four species: Vitex agnuscastus, Vitex negundo, vitex pinnata, and Vitex trifolia in the family. Later on, Verbenaceae Vitex along with several other genera was transferred from Verbenaceae to

Lamiaceae in the 1990s on the basis of phylogenetic studies of DNA sequences. The drug has effectively been employed for the treatment of waja-ul-mafasil (arthritis), warm-e- khussiyatain (orchitis), warm-e-reham (cervicitis), warm-e-miqad (proctitis), warm-e-tihal, bawaseer (haemorrhoids), warm-e-shobetein (bronchitis), zeequnnafs (asthma) etc. (Chantaranothai, 2011; Khare, 2007; Ladda and Magnum, 2012; Mahalakshmi et al., 2010; [7, 19, 21, Anonymous, 2007; Nadkarni, 2007; Ghulam, 2007; Hakeem, 2002; Kabiruddin, 2000) 22, 4, 28, 16, 17] .

Correspondence Saad Ahmed Consultant (Unani), Central Fig 1: Leaves of Sanbhaloo Council for Research in Unani Medicine, Ministry of AYUSH, Govt. of India ~ 330 ~ The Pharma Innovation Journal

Vernacular Names : Sanbhaloo Arabic : Aslag, Fanjangaht, Zukhamsateasabea, (Ahuja et al., 2015; Sharma et al., 2005; Anonymous, 2007; Zukhamsatilourag. Nadkarni, 2007; Hakeem, 2002; Kabiruddin, 2000; Khare, Assamese : Pasutia, Aggla-Chita, Pochatia, Aslok. 2007) [2, 35, 4, 28, 16, 17, 19] Bengali : Nirgundi, Nishinda, Nisinda, Beguna, Samalu : Sarsa, Samalu, Chasta, Nirgundi Description According To Unani Classical Literature Berar : Semalu The author of Khazain Ul Advia, Najmul Ghani mentions Bombayese : Katri, Lingu, Nargundu, Nirgundi, Nirgur, about two (2) varieties of the drug Nisinda, Shiwari 1. White Sanbhaloo, the flowers and leaves are whitish in Burmese : Kiyowbhanbin, Kiyubanbin color. Canarese : Bilenekki, Karilakki, Lakki, Lakkili, 2. Black Sanbhaloo, the flowers and leaves are blackish in Lekkigidda, Nekki, Niragundi, Nochi, Nukki, color Shurnboli Cantonese : King Tz, Wu Chi Ching Parts Used Chinese : Houng Kin, Mu Ching Leaves, Fruit, Seeds, Flower, Root, Bark etc. (Sharma et al., Deccan : Shamalu 2005; Anonymous, 2007; Nadkarni, 2007; Ghulam, 2007; English : Indian Privet, Five Leaved Chaste Tree Hakeem, 2002; Kabiruddin, 2000) [35, 28, 16, 17]. Gond : Nigri Gujrati : Nagoal, Nagda, Nagoda, Nagodz, Nigod, Nigari Mizaj Hasada : Huridaru . Hot 20 and Dry 20 (Anonymous, 2007; Nadkarni, 2007; : Mewri, Nengar, Nigori, Nirgandi, Nirgunda, Ghulam, 2007; Hakeem, 2002; Kabiruddin, 2000) [4, 28, 16, 17] Nisanda, Panikisambhalu, Sunbhal, Sambhalu, . Hot 20 and Dry 30 (Ghani, ynm) Shawali, Shiwali, Shiwari, Sinduca, Sinduara : Lakkingida, Lakkigida, Nakkilu, Nekki, Nekka, Dose Nakkigida, Lakki, Karillalaki (Dharwad), Tukham: Bilenekki (Mysore), Nochi, Sinduka, Sinduvara Up to 4 grams (Hakeem, 2002) [16] Kharwar : Sindwar 2-3 grams (Kabiruddin, 2000) [17] Kolami : Ehuri, Hobaro, Sinduari, Sindwor 3 grams (Ghulam, 2007) Koya : Vayila Table 1: Actions Kumaon : Shiwa, Shiwali, Simali Kurku : Nirgundi Action Reference Malaya : Ching Tzu, Huang Ching, Kheng Chee, Man Dafa-e-Ta’ffun Kabiruddin, 2000 [17]; Ghani,ynm; Ching (Antiseptic) Anonymous, 2008 [5] : Indrani, Nochi,Vellanochi, Vennochi Hazim (Digestive ) Ghani,ynm; Ghulam,2007; Nadkarni,2007 Manipuri : Urik shibi [28]; Kabiruddin, 2000 [17]; Kirtikar and Marathi : Lingur, Nirguda, Nirgunda, Nirgundi, Nirgur Basu, 2005 [20] Mundari : Bigana, Huri, Huhari, Sursing Jali (Detergent ) Anonymous, 2008 [5] Naguri : Huhuridaru Kasir-e-Riyah Kirtikar and Basu, 2005 [20]; Kabiruddin, Nepalese : Sewali (Carminative ) 2000 [17] [20] Oriya : Beyguna, Begundia, Nirgundi, Laguni Muqawwi-e-Asab Kirtikar and Basu, 2005 (Malkangiri), Begna, Beguniy (Nervine tonic) Muqawwi-e-Bah Ghani, ynm; Kirtikar and Basu, 2005 [20]; : Marvandaey, Nirgud, Kalgari (Aphrodisiac) Kabiruddin,2000 [17]; Persian : Banjangast, Panjangusht, Sisban Mulattif Kabiruddin, 2000 [17];Hakeem, 2002 [16]; : Angnocasto, Lagundi, Dabtan, Dangla Ghani,ynm Punjabi : Bankahu, Banna Binna, Biuna, Marwa, Muqawwi-e-Basar Kabiruddin, 2000 [17]; Ghani,ynm Marwan, Mawa Maura, Mora, Morann, (Eye Tonic) Moraun, Sanake, Shwari, Swanjan, Torbanna, Mohallil-e-Auram Kabiruddin, 2000 [17]; Anonymous,2008 [5]; Wana Sulba (Resolvent ) Anonymous,1997; Hakeem, 2002 [16]; Pushtu : Marwandai, Mehrwan, Warmande Ghani,ynm Sadani : Senduar Mufatteh (Exhilarant) Kabiruddin, 2000 [17]; Hakeem, 2002 [16] Saharanpur : Malla Mujaffif ( Desicant ) Kabiruddin,2000 [17] [28] : Indrani, Nilapushpa, Nilanirgundi, Nirgundi, Mushtahi (Appetizer) Ghani,ynm;Nadkarni, 2007 [17] [16] Shephali, Sinduvura Surasa, Suvaha Mudir-e-Haiz Kabiruddin, 2000 ; Hakeem, 2002 ; (Emmenagogue) Kirtikar and Basu, 2005 [20] Santali : Sinduari Mudir-e-Baul Kabiruddin, 2000 [17]; Hakeem, 2002 [16]; Sinhalase : Nikka, Nilnikka, Sudunikka (Diuretic ) Sharma et al.,2005 [35] Tagalog : Lagundi, Malawin, Molawin Mukhrij-e-Deedan-e- Nadkarni,2007 [28]; Kirtikar and Basu, 2005 Telugu : Vaavili, Vaavilu, Tellavavaati, Tellavavilli, Ama [20] Vaavilu, Chirvaavili, Mella-Vavili, Vavalipadu, Musakkin (Analgesic) Hakeem, 2002 [16]; Kabiruddin, 2000 [17]; Veyala, Vavilli, Nalla Vavili, Vavilipadu Sharma et al.,2005 [35] Tamil : Nirkkundi, Nochi, Sinduvaram, Musakkin-e-Waja Kabiruddin, 2007; Ghani,ynm; Tiriburameriitan, Vellainochi, Vennochi Anonymous,1997; Hakeem, 2002 [16] Telugu : Nallavavilli, Sinduvaramu, Vavili, Vayila Qabiz (Constipative) Kabiruddin, 2000 [17]; Hakeem, 2002 [16]; Tulu : Bilenekki, Nekki Kirtikar and Basu, 2005 [20]; Ghani,ynm [20] Uriya : Begundia, Indrani Qatil-e-Deedan Ghani,ynm; Kirtikar and Basu, 2005 ; (Anthelmentic) Hakeem, 2002 [16] ~ 331 ~ The Pharma Innovation Journal

Table 2: Therapeutic Uses to a small tree. Vitex negundo is also known as the five-leafed

Clinical Indication Reference chaste tree or monk’s pepper. Its most striking feature centers Aatishak (Syphilis) Kirtikar and Basu, 2005 [20] on a cluster of five pointed leaves resembling a palm. It is an Atash (Thirst) Kirtikar and Basu, 2005 [20] erect, 2-5 m in height, slender tree with quadrangular Azm-e-Tihal Kabiruddin, 2000 [17]; Hakeem, 2002 [16]; branchlets. The leaves have five leaflets palmately arranged, (Spleenomegaly ) Kirtikar and Basu, 2005 [20]; Ghani,ynm which are lanceolate, acute, glabrous, 4-10 cm long, hairy Bites of poisonous Hakeem, 2002 [16]; Ghani,ynm; beneath and pointed at both ends. The terminal leaflet has a animal and insect Kabiruddin, 2000 [17]; long petiole whereas; the lateral ones have short petiole. Bawaseer Hakeem, 2002 [16]; Kabiruddin, 2000 [17]; Flowers are bluish purple in colour borne on axillary or (Haemorrhoids) Kirtikar and Basu, 2005 [20] terminal panicle upto 30 cm long. The fruit is succulent [20] Dard-e-Sar (Headach) Kirtikar and Basu, 2005 ; Ghani,ynm globose and black when ripe with four seeds, rounded and Haiza (Cholera) Kirtikar and Basu, 2005 [20]; Ghani, ynm; [28] about 4 mm in diameter (Meena et al., 2011; Sharma et al., Nadkarni, 2007 [35, 6] [20] 2005; Basri et al., 2014) . Humma (Fever) Kirtikar and Basu, 2005 ; Ghani,ynm Hudar (Rheumatism) Kirtikar and Basu, 2005 [20]; Scientific Classification Nadkarni,2007 [28] Kingdom : Plantae Ghanghara Qurooh Kirtikar and Basu, 2005 [20] Order : (Gangrenous wound) Family : Is’hal (Diarrhoea) Kirtikar and Basu, 2005 [20] Genus : Vitex Junoon Hakeem, 2002 [16] Species : negundo Juzam (Leprosy) Ghani, ynm; Kirtikar and Basu, 2005 [20] Khafkaan (Palpitation) Hakeem, 2002 [16] Leaves are palmately compound, petiole 2.5-3.8 cm long; 3-5 Mouch (Sprain) Kritikar and Basu, 2005 foliate; the middle leafletis petiolate; in trifoliate leaf, leaflet Deedan-e-Ama Kirtikar and Basu, 2005 [20] lanceolate or narrowly lanceolate, acute, entire or rarely (intestinal worms) crenate, middle leaflet 5-10 cm long and 1.6-3.2 cm broad, Qulai-e-Dahan Kabiruddin, 2000 [17] with 1-1.3 cm long petiolule, remaining two subsessile; in (Stomatitis) pentafoliate leaf inner three leaflets have petiolule and Qoolanj (Colitis) Kabiruddin, 2000 [17] remaining two sub-sessile; Odour is agreeably aromatic Qurooh wa Zakham Kirtikar and Basu, 2005 [20] surface glabrous above and tomentose beneath; texture, (Ulcer and Wound ) leathery. Soozak (Gonorrhea) Kirtikar and Basu, 2005 [20] [17] Waja-ul-Mufasil Kabiruddin, 2000 ; Kirtikar and Basu, Stem Bark: Bark occurs in channelled pieces, 0.3-0.5 cm (Arthralgia) 2005 [20] thick; outer surface yellowish grey, rough, lenticelular, Waja-ul-Meda Nadkarni,2007 [28]; Kirtikar and Basu, (Stomachic) 2005[20] longitudinally channeled and transversely cracked; inner Warm-e-Khussiyatain Kabiruddin, 2000 [17]; Kirtikar and Basu, surface darker than outer, blackish and smooth; fracture short (Orchitis ) 2005 [20]; Anonymous, 2008 [5] and splintery; taste slightly bitter. In transverse section the Warm-e-Raham Kabiruddin, 2000 [17]; Hakeem, 2002 [16]; bark shows well developed periderm and secondary phloem (Metritis) Kirtikar and Basu, 2005 [20]; elements. Anonymous,2008 [5] Warm-e-Miqad Kabiruddin, 2000 [17]; Kirtikar and Basu, Root: Roots are woody, fairly thick, 8-10 cm in diameter; (Proctitis) 2005 [20]; Anonymous, 2008 [5] external surface brownish, rough due to the presence of [17] [16] Warm-e-Tihal Kabiruddin,2000 ; Hakeem,2002 longitudinal fissures and a small rootlets. The bark is very [28] Warm-e-Shobetein Nadkarni, 2007 thin and corky portion can be scrapped off easily. Transverse (Bronchitis) section shows outer cork consisting of 12-20 rows of nearly Zeequnnafs (Asthma) Ghani, ynm; Nadkarni; 2007 [28] [20] cubical to rectangular cells, the cells of peripheral rows being Zukaam (Catarrh) Kirtikar and Basu, 2005 ; Nadkarni; [21] 2007 [28] thick walled but not lignified (Ladda and Magdum, 2012) . Zof-e-Ishteha Anonymous, 2006; Nadkarni, 2007 [28]; (Dyspepsia) Kirtikar and Basu, 2005 [20] Microscopic Examination Petiole shows single layered epidermishaving a number of Botanical Description unicellular, bicellular and uniseriate multicellular covering Habit and Habitat trichomes and also glandular trichomes with uni to tricellular Vitex usually grows from three to nine feet tall, but under stalk anduni to bicellular head; cortex composed of outer cultivation can develop to 20 feet tall. Nirgundi occur in collenchymatous tissue and inner 6-8 layers of tropical to temperate regions (up to 2200 m from east to west) parenchymatous tissue; collenchyma well developed in basal grows gregariously in wastelands and is also widely used as a region and gradually decreases in middle and apical regions; hedge-. This species is globally distributed in Indo- pericyclic fibres absent in basal region of petiole and present , cultivated in America, Europe, and West in the form of a discontinuous ring in apical region Indies. Within India, it is found throughout the greater part of surrounding central horse shoe shaped vascular bundle; a few India, ascending to an altitude of 1500 meters in the outer smaller vascular bundles present ventrally between arms of Himalayas. It is abundant in open-waste lands. (Ladda and central vascular bundle and two, or rarely three, bundles Magnum, 2012; Mahalakshmi et al., 2010; Parashant, 2014; situated outside the arms. Meena et al., 2011; Venkateswarlu, 2012; Khare, 2007; Ahuja et al.,2015; Basri et al., 2014) [21, 22, 30, 48, 19, 2, 6]. Lamina - shows single layered epidermis having mostly unicellular hairs, bi and multicellular and glandular trichomes Plant Description being rare; hypodermis 1 -3layered interrupted at places by 4- Vitex negundo is a woody, aromatic deciduous shrub growing 8 palisade layers containing chlorophyll; a large number of ~ 332 ~ The Pharma Innovation Journal

veins enclosed by bundle sheath traverse mesophyll; stomata Pharmacological Studies present only on the ventral surface, covered densely with Anti-Inflammatory and Analgesic Study trichomes; vein-islet and vein termination number of leaf are Mahalakshmi et al., (2010) [22] studied that the sub-effective 23-25 and 5-7respectively. dose of Vitex negundo potentiated anti-inflammatory activity of phenylbutazone and ibuprofen significantly in carrageenin Powder – It shows number of pieces or whole, uni,bi and induced hindpaw oedema and cotton pellet granuloma multicellular covering trichomes, glandular trichomes, models. The potentiation of anti-inflammatory activities palisade tissues with hypodermis, andupper and lower phenylbutazone and ibuprofen by Vitex negundo Linn. epidermis, xylem vessels with pitted walls (Anonymous, indicates that it may be useful as an adjuvant therapy along 2007) [4]. with standard anti-inflammatory drugs. In another study Yunos et al., and Jana et al., established anti-inflammatory Phytochemical Studies properties of Vitex negundo extracts in acute and sub-acute Leaves - hydroxy-3,6,7,3′,4′-pentamethoxyflavone; 6′-p- inflammation which are attributed to prostaglandin synthesis hydroxybenzoyl mussaenosidic acid; 2′-p- hydroxybenzoyl inhibition. mussaenosidic acid; protocatechuic acid; oleanolic acid; In some other study it had been found that Vitex negundo flavonoids; 5, 3′-dihydroxy-7,8,4′-trimethoxyflavanone;5,3′- extracts potentiated the result of commonly used anti- dihydroxy-6,7,4′- trimethoxyflavanone; viridiflorol; β- inflammatory drugs viz., ibuprofen and phenylbutazone, caryophyllene; sabinene; 4-terpineol; gamma-terpinene; analgesics such as meperidine, aspirin, morphine and caryophyllene oxide; 1 -oceten-3-ol; globulol; angusid; pethidine sedative-hypnotic drugs like pentobarbitone, casticin; vitamin-C; nishindine; gluco-nonitol; diazepam and chlorpromazine anti-convulsive drugs like phydroxybenzoic acid; sitosterol; betulinic acid [3β- diphenyl hydantoin and valporic acid. (Tendon et al., 2006; hydroxylup-20-(29)-en-28-oic acid]; ursolic acid [2β - Gupta et al.,1999; Diaz et al.,2003; Gupta et al.,1997; Rana hydroxyurs-12-en-28-oic acid]; n-hentriacontanol; β- and Rana, 2014) [39, 41, 42, 44, 14, 15, 11]. sitosterol; p-hydroxybenzoic acid . Anti Inflammatory, analgesic and antirheumatic activity detailed studies have established anti-inflammatory properties Seeds - 3β -acetoxyolean-12-en-27-oic acid; 2α, 3α- of Vitex negundo extracts in acute and sub-acute dihydroxyoleana-5,12-dien-28-oic acid; 2β,3α inflammation. Anti-inflammatory and pain suppressing diacetoxyoleana-5, 12-dien-28-oic acid; 2α, 3β-diacetoxy-18- activities of fresh leaves of the plant are attributed to hydroxyoleana-5,12-dien-28-oic acid; vitedoin-A; vitedoin-B; prostaglandin synthesis inhibition, antihistamine, membrane aphenylnaphthalene-type lignan alkaloid, vitedoamine-A; β- stabilizing and antioxidant activities (Telang et al., 1999; sitosterol; p-hydroxybenzoic acid; 5-oxyisophthalic acid; n- Ravishankar et al., 1985) [45, 32]. tritriacontane, n-hentriacontane; n-pentatriacontane; n- nonacosane ; 6-hydroxy-4-(4-hydroxy-3- methoxy-phenyl)-3- Antinociceptive Study hydroxymethyl-7-methoxy-3, 4-dihydro-2-naphthaldehyde. Gupta et al., (2005) [40] were studied that the tail flick test in rats and acetic acid induced writhing in mice were employed Essential oil of fresh leaves, flowers and dried fruits - δ- to study the antinociceptive activity of ethanolic leaf extract guaiene; guaia-3,7-dienecaryophyllene epoxide; of Vitex negundo Linn. (100, 250 and 500mg/kg, p.o). The ethylhexadecenoate; α-selinene; germacren-4-ol; effect was compared with meperidine (40 mg/kg, sc) in tail caryophyllene epoxide; (E)-nerolidol; β-selinene; α- flick method and aspirin (50 mg/kg, p.o) in writhing test as a cedrene;germacrene D; hexadecanoic acid; p-cymene and standard control respectively. An interaction with naloxone valencene. hydrochloride was also studied in tail flick method for its mechanism of central analgesic action. It showed significant Roots - 2β, 3α-diacetoxyoleana-5, 12-dien-28-oic acid; 2α,3α- analgesic activity in dose dependent manner in both the dihydroxyoleana-5,12-dien-28-oic acid; 2α,3β -diacetoxy-18- experimental models. It suggested that Vitex negundo Linn. hydroxyoleana-5,12-dien-28-oic acid; vitexin and isovitexin, possesses both central and peripheral analgesic activity. The negundin-A; negundin-B; (+)-diasyringaresinol; (+)- central analgesic action does not seem to be mediated through lyoniresinol; vitrofolal-E and vitrofolal-F, acetyl oleanolic opioid receptors. It may prove to be a useful adjuvant therapy acid; sitosterol. along with standard analgesic drug. (Ladda and Magdum, 2012; Parashant, 2014; Parasanna et al.,2014; Vishwanathanand Basavaraju, 2010; Meena et CNS Depressant Study al.,2010; Sharma et al., 2005; Basri et al., 2014; Khare,2007; Ladda and Magnum (2012) [21] showed a methanolic extract of Chowdhury et al., 1984; Dayal and singh, 2000; Gautam et the leaves of Vitex negundo Linn. was found to significantly al., 2008; Singh et al.,1999; Subramanian et al., 1979; potentiate the sleeping time induced by pentobarbital sodium, Saravanasingh et al.,2016) [21, 30, 49, 24, 25, 35, 6, 19, 8, 10, 12, 37, 38]. diazepam and chlorpromazine in mice.

Physicochemical Studies Antifungal Study Physical constants Values Sathiamoorthy et al., (2007) studied that bioactivity guided Foreign matter : Not more than 2 % fractionation of ethanolic extract of leaves of Vitex negundo Total ash : Not more than 8 % resulted in the isolation of new flavone glycoside along with Acid-insoluble ash : Not more than 1 % five known compounds. All the isolated compounds were Alcohol-soluble extractive : Not less than 10 % evaluated for their antimicrobial activities. The new flavone Water-soluble extractive : Not less than 20 % glycoside and compound 5 were found to have significant (Ladda and Magdum, 2012; Anonymous, 2007; Basri et al., antifungal activity against Trichophyton Mentagrophytes and 2014) [21, 4, 6]. Cryptococcus neoformans at 6.25 µg/m.

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Antioxidant Study and ethylhexadecenoate; In flowers oil α-selinene,germacren- Prabhu et al., (2010) studied that the antioxidant potency of 4-ol, carryophyllene epoxide and (E)-nerolidol while fruit oil Vitex negundo was investigated by all the fractions of Vitex showed β -selinene, α-cedrene, germacrene D and negundo exhibited a potent scavenging activity for (2, 2′- hexadecanoic acid as themain constituents which help for azino-bis 3-ethylbenzothiazoline-6-sulfuric acid) ABTS antibacterial activity (Ladda and Magdum, 2012; Adnaik et radicalcations in a concentration dependent manner, showing al., 2008) [21]. Chowdhury et al., (2009) studied that the zones a direct role in trapping free radicals. The polar fractions of of inhibition produced by the methanol extract, pet. ether and Vitex negundo possess potent antioxidant properties. Tandon carbon tetrachloride fractions were found to be 07-16 mm, 07- and Gupta have also reported similar antioxidant properties of 11 mm and 06-11 mm respectively at a concentration of 200 Vitex negundo Linn. in rats, by using ethanol induced µg/disc in case of 09bacterial strains and 02 fungal strains oxidative stress model. where standard kanamycin (30µg/disc)showed zone of The extracts also possess the ability to combat oxidative stress inhibition of 08-19 mm. Promient activity was found against by reducing lipid peroxidation owing to the presence of Bacillus subtilis (13-16 mm) by all of the fractions. Methanol flavones, vitamin C and carotene. Rooban et al.. evaluated the extract showed significant inhibition (09 -10 mm) against antioxidant and therapeutic potential of Vitex negundo Bacillus cereus, Pseudomonas aeruginosa, Salmonella typhi flavonoids in modulating solenoid-induced cataract and found Pet-ether and carbontetrachloride fractions showed most it to be effective (Tiwari et al., 2007; Mahalakshmi et prominent inhibitory action (zone of inhibition 11-18 mm) al.,2010) [46, 22]. against Bacillus megaterium, Bacillus subtilis, Salmonella Leaf extracts of Vitex negundo were determined to possess typhi and Vibrio mimicus in comparison to standard antibiotic anti-oxidant potential. The extracts were found to be useful in (Kanamycin,30µg/disc). decreasing levels of superoxide dismutase, catalase and Gupta et al., (2005) [40] was assessed using the minimum glutathione peroxidase in Freund’s adjuvant induced arthritic- inhibitory concentration assay. Through bioactivity-guided rats. This extract also possess the ability to fight oxidative fractionation, the fraction responsible for the antimicrobial stress by reducing lipid peroxidation because of the presence activity was determined. The toxicity profile, anti-oxidant and of flavones, vitamin C and carotene. Rooban measured the anti-inflammatory activity was evaluated using the antioxidant and therapeutic potential of Vitex negundo tetrazolium cellular viability, 2,2-diphenyl-1 -picrylhydrazyl flavonoidsin modulating solenoid-induced cataract and found and 5-lipoxygenase assays respectively. The antimalarial it to be effective (Tiwari et al.,2007; Devi et al., 2007; Vishal activity of the extracts and isolated compound was also et al,2005; Rooban et al.,2009; Muna singhe et al.,2001) [46, 47, investigated on the chloroquine-resistant gambian FCR-3 33, 26]. strain of Plasmodium falciparum using the tritiated hypoxanthine incorporation assay. Enzyme Inhibitory Study Root extracts of Vitex negundo showed inhibitory activity Antiallergic Study against enzymes such as lipoxygenase butyrylcholinesterase, Ladda and Magdum (2012) [21] showed that the ethanolic α-chymotrypsin, xanthine-oxidase, tyrosinase. HIV-type 1 extract of Vitex negundo have antiallergic activity against reverse transcriptase inhibitory activity of the aqueous extract immunologically induced degranulation of mast cells. It also of the aerial parts of Vitex negundo has also been reported inhibited edema during active paw anaphylaxis in mice. The (Kannan et al., 2012; Woradulayapinij et al., 2005; Tandon et extract significantly inhibited both the initial and later al., 2005; Rana and Rana, 2014) [18, 50, 40]. sustained phases of tracheal contractions. The initial phase was primarily due to histamine and the latter phase was due to Anticonvulsant Study release of lipid mediators from arachidonic acid. Inhibition of Maximal electroshock seizures (MES) in albino rats and the latter phase may be secondary to inhibition of arachidonic pentylenetetrazole (PTZ) induced seizures in albino mice acid by the ethanolic extract. were used to study anticonvulsant activity of Vitex negundo Linn. Leaf extract. The test drug dose (1000 mg/kg, Snake Venom Neutralization Study p.o)showed 50% protection in clonic seizures and 24-hour The methanolic root extracts of Vitex negundo and Emblica mortality against PTZ induced seizures. It also decreased officinalis showed antisnake venom activity. The plant Vitex number and duration of convulsions significantly. Vitex negundo Linn. extracts significantly antagonized the Vipera negundo Linn. Potentiated anticonvulsant activity of valporic russellii and Naja kaouthiavenom induced lethal activity both acid. The anticonvulsant activity of Vitex negundo Linn. in in vitro and invivo studies. Vipera russellii venom-induced Hasnot been found equi-effective with standard drugs. haemorrhage, coagulant, defibrinogenating and inflammatory Moreover, the potentiation of diphenylhydantoin and valproic activity were significantly neutralized by both plant extracts. acid by Vitex negundo Linn. indicates that it may be useful as No precipitating bands were observed between the plant an adjuvant therapy along with standard anticonvulsants and extract and snake venom (Mahalaxmi et al.,2010; Alam et al., can possibly lower the requirement of diphenylhydantoin and 2003; Gupta et al., 2005) [3, 40]. valporic acid (Alam et at, 2003; Mahalaxmi et al.,2010; Tandon et al, 2005) [3]. Reproductive Potential Study The flavonoids rich fractions of seeds of Vitex negundo Linn. Antibacterial Study Caused disruption of the latter stages of spermatogenesis in Essential oils and successive ethyl acetate and ethanol extracts dogs and interfered with male reproductive function in rats. It of Vitex negundo Linn. showed antibacterial activity against must however be noted that these findings are in sharp Staphylococcus aureus, Bacillus subtilis, Escherichia coli and contrast with the traditional use of Vitex negundo Linn. as Pseudomonas aeruginosa bacterial strains. Main constituents aphrodisiac. Ethanolic extracts of Vitex negundo Linn. identified in leaves oil were guaiene, caryophyllene epoxide Showed estrogen-like activity and propounded its use in

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hormone replacement therapy (Das et al., 2004; Ladda and synthesis of novel and more potent analogues (Rastogi et al., Magdum, 2012; Prashant, 2014) [21, 30]. 2009) [31].

Histomorphological and Cytotoxic Study Reference Tandon and Gupta (2004) studied the histomorphological 1. Adnaik RS, Pai PT, Mule SN, Naikwade NS, Magdum effect of Vitex negundo Linn. extracts in rats and found the CS. Laxative Activity of Vitex negundo Linn. Leaves. stomach tissue to be unaffected even by toxic doses; while Asian J. Exp. Sci. 2008; 22(1):159-160. dose-dependent changes were observed in the heart, liver and 2. Ahuja SC, Ahuja S, Ahuja U. Nirgundi (Vitex negundo) - lung tissues. Cytotoxic effect of leaf extracts of Vitex negundo Nature’s Gift to Mankind. Asian Agri-History. 2015; Linn. was tested and affirmed using COLO-320 tumour cells. 19(1):5-32. On one hand, Diaz et al., (2003) [11] found the chloroform 3. Alam MI, Gomes A. Snake venom neutralization by extracts of Vitex negundo leaves to be toxic to a human cancer Indian medicinal (Vitex negundo and Embelica cell line panel (Sharma et al., 2006; Ladda and Magdum, officinalis) root extracts. J. Etanopharmacol. 2003; 2012; Prashant, 2014) [14, 21, 30]. 86(1):75-80. 4. Anonymous. The Unani Pharmacopoeia of India, Part – I, Hepatoprotective Study Volume – III. Central Council for Research in Unani The ethanolic extract of Vitex negundo at 250 and 500 mg/kg Medicine, New Delhi, 2007, 90-92. doses significantly decrease Serum Bilirubin, Aspartate 5. Anonymous. The Unani Pharmacopoeia of India, Part – I, Aminotransferase (AST), Alanine Aminotransferase (ALT), Volume – V, Central Council for Research in Unani Alkaline Phosphates (ALP) and Total Protein(TP) levels Medicine, New Delhi, 2008, 77-79. against hepatotoxicity (HT) produced by administering a 6. Basri F, Sharma HP, Firdaus S, Jain P, Ranjan A. A combination of three antitubercular drugs isoniazide (7.5 Review of Ethnomedicinal Plant-Vitex negundo Linn. mg/kg), rifampin (10 mg/kg) and pyrazinamide (35 mg/kg). International Journal of Advanced Research. 2014; Alcoholic extract of the seeds of Vitex negundo Linn. showed 2(3):882-894. the hepatoprotective action against carbon tetrachloride 7. Chantaranothai R. A revision of the genus Vitex induced liver damage. The extract was found to be effective (Lamiaceae) in . Tropical Natural History. 2011; in preventing liver damage which was evident by 11(2):91-118. morphological, biochemical and functional parameters 8. Chowdhury B, Dutta US, Pakrashi PK. Twoisomeric (Prashant, 2014) [30]. flavonones from Vitex negundo Linn. Phytochemistry. Nirgundi exerts a protective effect on CYP2E1 -dependent 1984; 23:703. CCl4 toxicity via inhibition of lipid peroxidation, followed by 9. Das S, Parveen S, Kundra CP, Pereira BM. Reproduction an improved intracellular calcium homeostasis and inhibition in male rats is vulnerable to treatment with the flavonoid- of Ca2+ dependent proteases (Tendon et al.,2004; Sheikh et rich seed extracts of Vitex negundo. Phytother Res. 2004; al., 2008; Tandon et al., 2008) [36, 43] 18(1):8-13. 10. Dayal R, Singh VA. Comparative study of volatile Hypoglycemic Study constituent of Vitex negundoLeaves. J med Aromat Plant Villasenor and Lamadrid (2006) [39, 41, 42] have provided an Sci. 2000; 22:639-640. account of the antihyperglycemic activity of Vitex negundo 11. Diaz F, Chávez D, Lee D, Mi Q, Chai HB, Tan GT et al. Leaf extracts. Cytotoxic Flavone Analogues of Vitexicarpin, a Constituent of the Leaves of Vitex negundo. Journal of Laxative Study Natural Products. 2003; 66:865-867. The aqueous extract of the Vitex negundo Linn. leaves at 12. Gautam LN, Shrestha SL, Wagle P, Tamrakar BM. doses 100 and 200mg/kg was investigated for laxative activity Chemical constituents from Vitex negundo (linn.) of according to Cappaso et al. in albino rats were compared with Nepalese origin. Scientific World. 2008; 6:6. standard drug agar-agar (300 mg/kg,p.o.) in normal saline. 13. Ghani N. (ynm). Khazain-ul-Advia, Idara Kitabul Shifa. The result showed laxative activity (Prashant, 2014; Ladda New Delhi, 835-836. and Magdum, 2012) [30, 21]. 14. Gupta M, Mazumder UK, Bhawal SR, Swamy SMK. CNS Activity of Petroleum Ether Extract of Vitex Immunomodultory Study negundo Linn. in Mice. Indian Journal of Pharmaceutical Immunomodulatory effect of Vitex negundo Linn. extracts has Sciences. 1997; 59:240-245. been reported by Ravishankar et al., (1985) [32] The decoction 15. Gupta M, Mazumder UK, Bhawal SR, Swamy SMK. of leaves is considered as tonic, vermifuge and is given along CNS Activity of Petroleum Ether Extract of Vitex with long pepper in catarrhal fever (Adnaik et al.,2008; negundo Linn. in Mice. Indian Journal of Pharmaceutical Prashant, 2014) [30]. Sciences. 1997; 59:240-245. 16. Hakeem A. Bustan-ul-Mufredat, Idara Kitab-ul-Shifa. Biological Study Dariya Ghanj, Delhi 110002; 2002, 343 Vitex negundo has shown promise as an effective bio-control 17. Kabiruddin H. Makzan ul Mufradat. Aijaz Publishing agent. The extracts of Vitex negundo Linn. Possess inhibitory, House, Delhi, 2000, 358-359. deterrent or lethal activity on biological agents that cause 18. Kannan M, Rajendran P, Vedha V, Ashok G, Anushka S, disease and damage to other organisms Additionally, Ramachandran Nair PC. HIV-1 Reverse Transcriptase production of plant secondary metabolites de novo, by in vitro Inhibition by Vitex negundo L. Leaf Extract and cell culture methods, has assumed importance in the last two Quantification of Flavonoids in Relation to Anti- decades because the structural complexity of naturally HIVActivity. Journal of Cell and Molecular Biology. occurring metabolites forms the basis for the chemical 2012; 10:53-59.

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19. Khare CP. Indian Medicinal Plants an Illustrated 35. Sharma PC, Yelne MB, Dennis. Database On Medicinal Dictionary. Springer-Verlag Berlin/Heidelberg. 2007; Plants Used In Ayurveda, Central Council for Research 493:710. in Ayurveda and Siddha, New Delhi; 2005; 3:450-455. 20. Kirtikar, Basu. Indian Medicinal Plants, 2nd edition, 36. Sheikh AT, Kaiser PJ, Gupta BD, Gupta VK, Johri RK. International Book Distributors, Dehradun; 2005; Negundoside, an irridiod glycoside from leaves of Vitex l3:1937-1941. negundo, protects human liver cells against,calcium 21. Ladda PL, Magdum CS. Vitex negundo Linn. : mediated toxicity induced by carbon tetrachloride. World Ethnobotany, Phytochemistry and Pharmacology- A J Gastroenterol. 2008; 14(23):3693-3709. Review. International Journal of Advances in Pharmacy, 37. Singh V, Dayal R, Bartley JP. Volatile Constituents of Biology and Chemistry APBC. 2012; 1(1):111-120. Vitex negundo Leaves. Planta Med Letters. 1999; 65:580- 22. Mahalakshmi R, Rajesh P, Ramesh N, Balsubramanian 582. V, Kanan VR. Hepatoprotective activity on Vitex 38. Subramanian PM, Misra GS. Flavonoids of Vitex negundo Linn.(Verbanaceae) by using wistar albinorats negundo. J. Nat. Products. 1979; 42(5):540-542. in Ibuprofen induced model. International journal of 39. Tandon VR, Gupta RK. Anti Inflammatory Activity and pharmacology. 2010, 1-6. Mechanism of Action of Vitex negundo Linn. 23. Meena AK, Niranjan US, Rao MM, Padhi MM, Ramesh International Journal of Pharmacology. 2006; 2:303-308. Babu. A review of the important chemical constituents 40. Tandon VR, Gupta RK. An experimental evaluation of and medicinal uses of Vitex genus. Asian Journal of anticonvulsant activity of Vitex negundo. Indian J Physiol Traditional Medicines. 2011; 6(2). Pharmacol. 2005; 49(2):199-205. 24. Meena AK, Singh U, Yadav AK, Singh B, Rao MM. 41. Tandon VR, Gupta RK. Vitex negundo leaf extract as an Pharmacological and Phytochemical Evidences for the adjuvant therapy tostandard Anti Inflammatory drugs. Extracts from Plants of the Genus Vitex - A Review. Indian JMed Res. 2006; 124(4):447-50. International Journal of Pharmaceutical and Clinical 42. Tandon VR, Gupta RK. Vitex negundo leaf extract as an Research. 2010; 2(1):01-09. adjuvant therapy to standard anti inflammatory drugs. 25. Meena AK, Singh U, Yadav AK, Singh B, Rao MM. Indian J Med Res. 2006; 124(4):447-50. Pharmacological and Phytochemical Evidences for the 43. Tandon, VR, Khajuria V, Kapoor B, Kaur D, Gupta S. Extracts from Plants of the Genus Vitex - A Review. Hepatoprotective activity of Vitex negundo leaf extract International Journal of Pharmaceutical and Clinical against antitubercular drugs induced hepatotoxicity. Research. 2010; 2(1):01-09. Fitoterapia. 2008; 29(7-8):533-538 26. Munasinghe TCJ, Seneviratne CK, Thabrew MI, 44. Gupta M, Mazumder UK, Bhawal SR. 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