Chinese Journal of

Natural Chinese Journal of Natural Medicines 2017, 15(11): 08010815 Medicines

doi: 10.3724/SP.J.1009.2017.00801

The : Phytochemistry and pharmacology

SHANG Zhan-Peng1Δ, WANG Fei1Δ, ZHANG Jia-Yu2*, WANG Zi-Jian2, LU Jian-Qiu3, WANG Huai-You4, LI Ning4*

1 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China; 2 Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; 3 Library of Beijing University of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; 4 Shenzhen Research Institute, Hong Kong University of Science and Technology, Shenzhen 518057, China

Available online 20 Nov., 2017

[ABSTRACT] Liriope () have been used as folk medicines in Asian countries since ancient times. From Liriope (8 species), a total of 132 compounds (except polysaccharides) have been isolated and identified, including steroidal saponins, flavonoids, phenols, and eudesmane sesquiterpenoids. The crude extracts or monomeric compounds from this genus have been shown to exhibit anti-tumor, anti-diabetic, anti-inflammatory, and neuroprotective activities. The present review summarizes the results on phytochemical and biological studies on Liriope plants. The chemotaxonomy of this genus is also discussed.

[KEY WORDS] Liriope; Liliaceae; Chemical constituents; Biological activities [CLC Number] R284, R96 [Document code] A [Article ID] 2095-6975(2017)11-0801-15

The effects of its root extracts in preventing obesity, diabetes, Introduction and neurodegenerative diseases have also been proven re- There has been a long history in the discovery, cultiva- cently [6-9]. As substitutes for japonicus, L. mus- tion and utilization of medicinal plants in most developing cari (Duanting Shanmaidong) and L. spicata (Hubei Maidong) countries. Even nowadays, the people there still rely on me- are widely used as remedies for various inflammation-related dicinal plants for primary health care directly or indirectly. diseases, such as pharyngitis, bronchitis, pneumonia, and Among the well-known medicinal plants and herbs, species cough, and cardiovascular diseases [4, 9-12]. L. graminifolia has from genus Liriope play an important role in protecting the been used as a popular remedy for the treatment of cancer [13]. well-being of Asian people. According to ‘Flora of China’, Besides, modern pharmacological studies have demonstrated genus Liriope (Liliaceae) mainly consists of 8 species that are the biological activities of Liriope plants for the treatment of distributed in subtropical and temperate zones, such as China, gastrelcosis [14], as well as neuroprotective [14], hepatoprotec- [1-3] Japan, Vietnam, and Philippines . tive [14], anti-inflammatory [15], antibacterial [16] effects. Various species of genus Liriope have been used as tradi- Therefore, the documented information on medicinal use of tional medicines for treating various diseases. As perennial Liriope plants provides valuable clues for the further bio- plants, L. platyphylla is a well-known herbal medicine for the prospecting and clinical applications [17]. [4-5] treatment of asthma and bronchia and lung inflammation . As an effort to facilitate the related therapeutic and pharmacological research of Liriope plants, this review

comprehensively describes their chemical compositions and [Received on] 12-Nov.-2016 pharmacological and biological activities. The chemotax- [Research funding] This work was supported by the National Natu- ral Science Foundation of China (Nos. 81303206 and 81303189). onomic significance and further research prospects are also [*Corresponding authors] Tel: 86-10-64287540, E-mail: discussed. [email protected] (ZHANG Jia-Yu); Tel: 86-852-23587338, E-mail: [email protected] (LI Ning). Chemical Constituents of Liriope Plants ΔThese authors contributed equally to this work. [7] These authors have no conflict of interest to declare. A total of 132 compounds (except polysaccharides ) have

– 801 – SHANG Zhan-Peng, et al. / Chin J Nat Med, 2017, 15(11): 801815 been isolated and identified from various Liriope plants so far. and the other components (Figs. 1, 2, 3, 4, and 5 and Tables 1, These constituents are of five categories, namely, steroidal 2, 3, 4, and 5). Among them, steroidal saponins are the domi- saponins, flavonoids, phenols, eudesmane sesquiterpenoids nant constituent in Liriope plants.

Fig. 1 Structures of steroidal saponins from genus Liriope

Phytochemical studies on Liriope plants have led to the mixed steroidal saponins) [18]. In addition, 21 steroidal saponins isolation and structural characterization of 46 steroidal saponins have been isolated from L. musacari. To our surprise, there are (Table 1). From the subterranean part of L. platyphylla, 10 ster- three furostanol sponins (8, 36 and 44) in L. platyhylla which oidal saponins have been isolated (compounds 5 and 6 were are previously reported to be abundant in Ophiopogon plants.

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Fig. 2 Structures of flavonoids from genus Liriope

Besides, 37 flavonoids, including homoisoflavones, an- time from L. platyphylla [35]. Besides, 19 phenols have been thocyanidins, chalcones, flavones, isoflavanones, and fla- isolated from L. . Absolute configuration of com- vonols, have been isolated and identified from Liriope plants. pounds 92−94 are comprehensively determined by 1D, 2D Among them, there are 16 homoisoflavanones (50−61, 70 and NMR, CD and MS spectral data analysis [40]. In addition, 6 81−83) which exhibit remarkable pharmacological activities. eudesmane sesquiterpenes have been isolated from Liriope Among them, compounds 54−59 are identified for the first plants. Of them, two new cis-eudesmane sesquiterpene

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Fig. 3 Structures of phenols from genus Liriope

Fig. 4 Structures of eudesmane sesquiterpene glucosides from genus Liriope glycosides from tubers of L. muscari (104 and 107) are iso- pounds from Liriope plants have been investigated [46-48]. The lated and identified via NMR and HR-ESI-MS analysis [42] results form the basis of further study on the cellular and mo- whereas compound 108 is characterized by NOSEY, ROESY lecular impacts of L. platyphylla root extract on human cancer and CD spectral analysis [43]. And 24 other constituents, in- cell lines. For example, a study has shown that the fractions cluding amides, fatty acids, alkaloids, dihydrobenzofuroiso- extracted from the L. platyphylla root part (LPRP-9) might coumarins, have been identified from Liriope plants. Among inhibit proliferation of tumor lines MCF-7 and Huh-7 and them, compounds 130 and 131 are isolated for the first time from down-regulate the phosphorylation of AKT [48]. The results the L. muscari and exhibit significant antioxidant activity [34]. have demonstrated that LPRP-9 could be developed as an anti-tumor adjuvant. Biological Activities of Liriope Plants Cytotoxicities of compounds isolated from Liriope plants Antitumor activity have been tested on various cancer cell lines. For instance, Anti-tumor activities of extracts and monomeric com- DT-13 (mixture of 16 and 30 from L. muscari) exhibit

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Fig. 5 Structures of other compounds from genus Liriope significant in vitro and in vivo anti-tumor effects [49]. The Hypoglycemic activity study on the ability of Ophiopogonin B (Op-B) to suppress in The great hypoglycemic effect has been reported from L. non-small cell lung cancer (NSCLC) lines NCL-H167 and platyphylla and L. spicata. Their roots are usually adopted as NCL-H460 [50] have demonstrated that Op-B might be a pro- a popular Chinese folk medicine for the treatment of diabetes. spective inhibitor of PI3K/Akt to induce autophagy in cells. For example, to compare the hypoglycemic effect of different Meanwhile, many steroidal saponins and favonoids exhibit L. spicata extracts, systematic experiments have been carried remarkable bioactivities against lung cancer, cervical cancer, out on diabetic animals [54]. Rats were orally administrated and liver cancer cell lines, etc. Table 6 shows the effects of with polysaccharide extract, steroidal saponin extract, total different constituents from Liriope plants on various cancer extract, diamicron (a common hypoglycemic agent) and cell lines [26, 30, 34, 49-52]. It has been revealed that the introduc- equivalent normal saline (control group). There was a signifi- tion of a hydroxyl group to C-17 on the aglycone moiety does cant difference between four drug groups and control group. not significantly influence their activities, whereas the at- Furthermore, it was demonstrated that L. platyphylla could tachment of a C-14 a hydroxyl group to the aglycone moiety stimulate insulin secretion, decrease lipid in serum and inhibit considerably reduces the cytotoxicity [53]. Although it may be fatty liver formation by regulating fatty acid oxidation [55]. useful for exploring the structure-activity relationship of some Related studies have been also carried out to confirm it [56-58]. steroidal saponins, more information remains to be needed for In-depth studies, especially at the molecular level, are in ur- further studies. gent need in order to clarify their mechanisms.

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Table 2 Flavonoids from genus Liriope

No. Names Plants Part References

47 Hesperidin L. graminifolia Root tuber [26]

48 7,4′- dihydroxy -5- methoxy-flavanonol L. graminifolia Root tuber [26]

49 5,7-dihydroxy-8-mthoxy-flavone L. graminifolia Root tuber [34]

50 (3S)-3,5,4′-trihydroxy-7-methoxy-6-methyl-homoisoflavanone L. musacari Root tuber [34]

51 5,7-dihydroxy-3-(4-methoxybenzyl)-6-methyl-chroman-4-one (OphiogonanoneB) L. graminifolia Subterranean [26]

52 (3R)-5,4′-dihydroxy-7-methoxy-6-methyl-chroman-4-one (Liriopein A) L. platyhylla Root tuber [35]

53 (3R)-5,2′,4′-trihydroxy-7-methoxy-6-methyl-chroman-4-one (Liriopein B) L. platyhylla Root tuber [35]

54 (3R)-3-(4′-hydroxybenzyl)-5,7-dihydroxyl-chroman-4-one L. platyhylla Root tuber [35] (3R)-3-(4′-hydroxybenzyl)-5,7-dihydroxy-6-methyl-chroman-4-one 55 (3R)-3-(2′,4′-dihydroxybenzyl)-5,7-dihydroxy-chroman-4-one L. platyhylla Root tuber [35] (3R)-3-(2′,4′-dihydroxybenzyl)-5,7-dihydroxy-6-methyl-chroman-4-one 56 (3R)-3-(4′-hydroxybenzyl)-3,5-dihydroxy-7-methoxy-6-methylchroman-4-one L. platyhylla Root tuber [35]

57 3-(4′-hydroxybenzylidene)-5,7-dihydroxy-chroman-4-one L. platyhylla Root tuber [35]

58 3,5- dihydroxy-7-methoxy-3-(4-hydroxybenzy)-chroman-4-one L. platyhylla Root tuber [36]

59 3,5-dihydroxy-7-methoxy-6-methyl-3-(4-hydroxybenzy)-chroman-4-one L. platyhylla Root tuber [36]

60 Isoliquiritigenin L. musacari Root tuber [35]

61 Kaempferol L. musacari Root tuber [37]

62 3-O-methylquercetin L. platyhylla Root tuber [37]

63 3,3′-O-dimethylquercetin L. platyhylla Aerial part [37]

64 3,4′-O-dimethylquercetin L. platyhylla Aerial part [37]

65 Kaempferol-3-O-Glucoside L. platyhylla Aerial part [37]

66 Quercetin-3-O-Glucoside L. platyhylla Aerial part [37]

67 Isorhamnetin-3-O-Glucoside L. platyhylla Aerial part [37]

68 3-(2′,4′-dihydroxybenzyl)-5,7-dihydroxy-6-methylchroman-4-one L. platyhylla Aerial part [37]

69 Isorhamnetin-3-O-glucoside L. platyhylla Aerial part [37]

70 7,4′-dihydroxy-5-methoxy-flavanonol L. platyhylla Aerial part [37]

71 Liquiritigenin L. platyhylla Aerial part [37]

72 Diosmetin L. platyhylla Aerial part [37]

73 Delphinidin-3-O-Glucoside L. platyhylla [38]

74 Delphinidin-3-O-Rutinoside L. platyhylla Fruit [38]

75 Cyanidin-3-O-Glucoside L. platyhylla Fruit [38]

76 Petunidin-3-O-Glucoside L. platyhylla Fruit [38]

77 Petunidin-3-O-Rutinoside L. platyhylla Fruit [38]

78 Malvidin-3-O-Glucoside L. platyhylla Fruit [38]

79 Malvidin-3-O-Rutinoside L. platyhylla Fruit [38]

80 6-C-methylquercetin-3-methylether L. platyhylla Aerial part [37]

81 Disporopsin L. platyhylla Aerial part [37]

82 3-(2′,4′-dihydroxy-benzyl)-5,7-dihydroxy-6-methyl-chroman-4-one L. platyhylla Aerial part [37]

83 Methylophiopogonanone B L. graminifolia Root tuber [26]

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Table 3 Phenols from genus Liriope No. Names Plants Part References 84 Emodin L. musacari Root tuber [36] 85 Syringaresinol L. platyhylla Root tuber [35, 37] 86 4-Allylpyrocatechol L. spicata Root tuber [39] 87 2,6-Dimethoxy-4-nitrophenol L. spicata Root tuber [39] 88 Vanillic acid L. spicata Root tuber [27, 39] 89 trans-p-Hydroxycinnamic acid L. spicata Root tuber [39] 90 Syringic acid L. spicata Root tuber [39] 91 4-Hydroxy-benzaldehyde L. platyhylla Root tuber [35, 39] 92 (−)-Pinoresinol L. musacari Root tuber [35, 40] 93 (2S,3R)-Methyl-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-2, L. musacari Root tuber [39, 40] 3-dihydrobenzofuran-5-carboxylate 94 (4R,5S)-5-(3-Hydroxy-2,6-dimethylphenyl)-4-isopropyldihydrofuran-2-one L. musacari Root tuber [39, 40] 95 2-(4′-Hydroxybenzyl)-5,6-methylenedioxy-benzofuran L. spicata Root tuber [39] 96 2-(4′-Hydroxy-benzoyl)-5,6-methylenedioxy-benzofuran L. spicata Root tuber [39] 97 (+)-Platyphyllarin A L. platyhylla Root tuber [35, 37] Aerial part [37] 98 (+)-Platyphyllarin B L. platyhylla Root tuber [35, 37] 99 (2R)-(2',4'-Dihydroxybenzyl)-6,7-methylenedioxy-2,3-dihydroben-zofuran L. platyhylla Aerial part [37] 100 3-(2'-Hydroxyphenyl)-6,8-dihydroxy-7-methoxy-isocoumarin L. platyhylla Aerial part [37] 101 Platyphyllarin C L. platyhylla Aerial part [37] 102 Vanillin L. platyhylla Aerial part [37] L. spicata Root tuber [35]

Table 4 Eudesmane sesquiterpene glucoside from genus Liriope No. Names Plants Part References 103 1,4-epoxy-cis-Eudesm-6-O-β-D-glucopyranoside L. musacari Root tuber [41] 104 1β, 6β-Dihydroxy-cis-eudesm-3-ene-6-O-β-D-glucopyranoside (Liriopeoside A) L. musacari Root tuber [41] 105 1β,6β-Dihydroxy-cis-eudesm-3-ene-6-O-β-D-glucopyranoside L. musacari Root tuber [41, 42] 106 1α,6β-Dihydroxy-5,10-bis-epi-eudesm-4(15)-ene-6-O-β-D-glucopyranoside L. musacari Root tuber [41] 107 Ophiopogonoside A L. musacari Root tuber [42, 43] 108 Ophiopogonoside B L. musacari Root tuber [43]

Table 5 Other types of constituents from genus Liriope No. Names Plants Part References 109 β-Sitosterol L. spicata Root tuber [21, 39, 44] 110 β-Sitosteryl palmitate L. musacari Root tuber [27] 111 β-Sitosteryl-β-D-glucopyranoside L. musacari, L. platyhylla Root tuber [35, 43, 45] 112 Stigmasterol L. spicata Root tuber [36] 113 Stigmasteryl palmitic L. musacari Root tuber [27] 114 Stigmasterol-β-D-glucoside L. platyhylla Root tuber [35] 115 Campesterol glucoside L. spicata Root tuber [27] 116 Pentacosane L. musacari Root tuber [27] 117 Hentriacontane L. musacari Root tuber [27] 118 Oleanolic acid L. musacari Root tuber [27] 119 Ursolic acid L. platyhylla Root tuber [27, 44]

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Continued No. Names Plants Part References 120 Glutaminsaeure anhydride L. musacari Root tuber [27] 121 Lupenone L. platyhylla Root tuber [44] 122 Lupeol L. platyhylla Root tuber [45] 123 N-Pentyl benzoate L. musacari Root tuber [28] 124 Palmitic acid glyceride L. musacari Root tuber [43] 125 Ethyltributanoate L. platyhylla Root tuber [35] 126 Palmitic acid L. musacari Root tuber [43, 44, 45] 127 4-Hydroxy-methyl benzoate L. platyhylla Root tuber [35] 128 5-Hydroxymethyl-2-furaldehyde L. spicata Root tuber [39] 129 N-trans-Coumaroyltyramine L. musacari Root tuber [34-36] 130 N-trans-Feruloyltyramine L. platyhylla Root tuber [34, 35] 131 N-trans-Feruloyloctopamine L. musacari Root tuber [34, 35] 132 Fatty acid derivative L. platyhylla Root tuber [35]

Table 6 Anti-tumor activity of constituents from Liriope plants against tumor cell lines Source Compound or extract Cell lines Result (μg·mL−1) References

L. graminifolia 25 SMMC-7721 IC50 76.4 ± 6.6 [26]

(Subterranean) 24 SMMC-7721 IC50 > 100 [26]

10 SMMC-7721 IC50 45.8 ± 5.4 [26]

7 SMMC-7721 IC50 > 100 [26]

83 SMMC-7721 IC50 34.6 ± 5.4 [26]

51 SMMC-7721 IC50 > 100 [26]

25 Hela IC50 26.1 ± 4.4 [26]

24 Hela IC50 18.6 ± 3.6 [26]

10 Hela IC50 13.3 ± 3.0 [26]

7 Hela IC50 40.6 ± 6.4 [26]

83 Hela IC50 6.0 ± 2.4 [26]

51 Hela IC50 14.0 ± 3.2 [26]

51 H157 IC50 2.86 [50]

51 H460 IC50 4.61 [50]

L. platyhylla Extract (70% ethanol) A549 IC50 > 100 [48]

(Root part) Huh-7 IC50 > 100 [48]

Hep 3B IC50 84.3 ± 1.0 [48]

MCF-7 IC50 67.7 ± 0.8 [48]

MDA-MB-231 IC50 57.6 ± 1.8 [48]

Extract A549 IC50 77.9 ± 1.9 [48]

Huh-7 IC50 36.0 ± 0.2 [48]

Hep 3B IC50 52.1 ± 2.2 [48]

MCF-7 IC50 23.1 ± 1.3 [48]

MDA-MB-231 IC50 72.2 ± 1.4 [48]

L. musacari DT-13 (16, 30) SMMC-7721 IC50 17 [47]

(Root part) Hela IC50 38 [47]

A549 IC50 67 [47]

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Continued Source Compound or extract Cell lines Result (μg·mL−1) References

L. spicata β-Sitosterol (109) SGC-7901 IC50 154.02 [51, 52]

(Root part) HO-8910 IC50 55.32 [51, 52] HCT-116 — [51, 52]

BEL-7402 IC50 17.81 [51, 52]

SMMC-7721 IC50 49.09 [51, 52]

L. musacari A mixture of 33 and 34 MDA-MB-435 IC50 0.58 ± 0.8 [30]

(Root part) 35 MDA-MB-435 IC50 0.05 ± 0.1 [30]

30 MDA-MB-435 IC50 > 100 [30]

7 MDA-MB-435 IC50 0.15 [30]

7 K562 IC50 18.6 [23]

7 HL60 IC50 16.5 [23]

Anti-inflammatory activity 53.33 μg·mL–1, respectively. In addition, the acidic methanol Previous studies have demonstrated that extracts and extract also exhibited 83.9% DPPH and 92.5% ABTS scav- constituents from Liriope plants exhibit distinct anti-inflamma- enging activities at a dose of 0.5 mg·mL–1 [38]. Furthermore, tory abilities [59]. For example, xylene-induced ear swelling the anti-oxidant activity of 7 types of anthocyanin (73−80) and paw edema mice were adopted to evaluate the anti-infla- isolated from L. platyphylla have been tested. Among mmatory activities of aqueous extract from L. muscari [60]. It them, Compounds 77 and 79 showed the highest activity. The showed remarkable anti-inflammatory effects in such two DPPH scavenging effects of 5 compounds and references animal models at a single oral dose of 23.2 and 4.6 mg·kg–1, were investigated and they decreased according to the fol- respectively. The therapeutic effect of aqueous extract of L. lowing order: VC > 131 > 130> BHT > 49 > 129 > 50 [66, 67]. platyphylla on atopic dermatitis has also been confirmed by Table 7 Anti-inflammation activity of constituents from Liriope using the luciferase report system in IL-4/Luc/CNS-1 trans- plants genic mice [61]. An inhaled treatment of L. platyphylla extract Compounds IC50 Source could weaken airway hyper responsiveness (AHR) in an ovalbumin-induced asthmatic mouse model [15]. Similar stud- 21 5.45 ± 0.26 L. spicata (Root part) ies about inflammatory pulmonary diseases [5, 62-63] have also 3 1.08 ± 0.03 L. spicata (Root part) been conducted to confirm this pharmacology property. 16 1.63 ± 0.16 L. spicata (Root part) In additional, the ability of DT-13 to inhibit carrageenan 11 1.13 ± 0.06 L. spicata (Root part) or histamine-induced acute inflammation has been investi- 17 1.51 ± 0.08 L. spicata (Root part) gated [61]. The reported results have demonstrated that DT-13 9 0.59 ± 0.02 L. spicata (Root part) could suppress acute inflammation and inhibit the adhesion of 38 — L. spicata (Root part) HL-60 to ECV304 cells in vitro. In another study, at doses of 10 and 20 mg·kg–1, DT-13 might resist ear swelling signifi- 39 — L. spicata (Root part) cantly [64]. Compound 16 might increase PMA-induced mucin 40 0.34 ± 0.01 L. spicata (Root part) secretion and stimulate basal mucin production, which indi- 95 4.15 ± 0.07 L. spicata (Root part) cated the ability to relieve pulmonary inflammation with the 96 5.96 ± 0.37 L. spicata (Root part) [65] mechanism of directly affecting airway epithelial cells . The neutrophil respiratory inhibitory activities of compounds Neuroprotective activity 3, 9, 11, 16, 17, 21, 38, and 39 from L. spicata [24] were con- The effects of 70% ethanol extract of L. platyphylla roots ducted (Table 7). have been investigated using behavioral and immunohisto- Anti-oxidant activity chemical methods in mice [68], which have demonstrated it has The dried powders of Liriope plants are frequently good ability to improve learning and memory and enhance used as tea drinks in Taiwan [66]. Different extracts, including BDNF or NGF expression. Besides, buthanol extract of L. hexane-soluble, ethylacetate-soluble and water-soluble of platyphylla might activate astroglial nerve growth factor Liriope plants, have been tested for their DPPH scavenging through a PKC-dependent pathway which contributed to the [14] activities using spectrophotometry [67]. The results have dem- induction of neurite outgrowth of PC12 cells . onstrated that ethylacetate-soluble fraction possessed the Total saponins extract of Liriope plants might affect the –1 highest DPPH scavenging activity with IC50 of SL, BL, and spontaneous activity of mice at a dose of 600 mg·kg , and TL for DPPH radical scavenging activity at 41.55, 24.55, and significantly reduce the caffeine sodium benzoate-induced

– 811 – SHANG Zhan-Peng, et al. / Chin J Nat Med, 2017, 15(11): 801815 excitable activity [69]. Current finding indicates that L. platy- 52, 53, 56, 57, 58, 97, 98, 125, and 130 have been undergone phylla extract exhibit neuroprotective effects against anti-platelet aggregation tests. Compounds 57 and 58 attrib-

H2O2-induced apoptotic cell death through modulating p38 uted to homoisoflavonids have shown greater anti-platelet activation in SH-SY5Y cells. Another research has shownthat potency than 52, 53, 55 and 58, suggesting a positive role for total saponins extract of L. platyphylla could improve the the C-2′ hydroxy moiety in enhancing the inhibitory effect on memory of senile mice induced by D-galactose, increase their platelet aggregation induced by collagen [35]. body weight, thymus and spleen indexes while the levels of Other activities methane dicarboxylic aldehyde (MDA) and lipofuscin are When given DT-13 to ICR mice, the liver injury de- decreased [70]. creased significantly [85]. The essential oil of L. muscari exhibited Laxative activity potent insecticidal activities against Tribolium castaneum, Lasio-

L. platyphylla has been used as a valid medicine in China derma serricorne and Liposcelis bostrychophila adults, with LD50 and Korea for the treatment of gastrointestinal (GI) disorders values of 13.36, 11.28 μg/adult and 21.37 μg/cm2 [86], respec- which are related to constipation and abnormal GI motility [71]. tively. Besides, L. platyphylla is also used as estrogen-rece- The laxative effect of aqueous extract of L. platyphylla ptor agonists [37]. Compounds 63, 64, 68, 80, and 97 exhibit has been tested on constipated SD rats [72]. The reported re- significant binding activity to estrogen-receptor α and/or β, as sults have demonstrated that the amounts of stool and urine demonstrated by the SEAP reporter assay system in MCF-7 excretion are significantly higher than those of control group cells. What is more, polysaccharides extract of Liriope plants while the food consumption and water intake remain at the could significantly increase the amount of salivary secretion, same level. Furthermore, RT-PCR and Western blot experi- spleen, thymus and submandibular glands index to against ments have revealed a dramatic reduction of key factors level sjogren syndrome [87]. on the muscarinic acetylcholine receptors (mAChRs) signal- Conclusions and Research Prospects ing pathway [73]. Immunoregulatory activity The abundant ingredients in Liriope plants have dis- Polysaccharide extract of Liriope plants [74] could relieve played extensive biological and pharmacological functions, the damage of cyclophosphamide-induced immune organ at a providing a scientific basis for their traditional therapeutic dose of 1 600 mg·kg-1 and increase the weight of immune effects. Herein we propose a few future investigations to bet- organ. Systematic experiments showed polysaccharide ex- ter understand its mechanisms of action and better its clinical tracts of L. muscari could significant enhance splenic index, use in the future. macrophage phagocytosis capacity, serum hemolysin, cyto- First, biological availabilities of steroidal saponins are kines (IL-2, TNF-α), NK cell activity and lymphocyte trans- relatively limited due to their large molecular weight [88-89]. formation ability [75-77]. Besides, another research has been Consequently, it is crucial to exploit new formulations to conducted in the lipopolysaccharide-induced cultured RAW increase their oral absorption. To a certain extent, L. muscari 264.7 mouse macrophages [78]. The results have demonstrated and L. spicata can be adopted as O. japonicus in clinic due to that water extract of L. platyphylla has the immunomodula- their similar pharmacological activities according to Chinese tory activity to reduce excessive immune reactions via acti- Pharmacopoeia. However, some distinct discrimination still vating macrophages. exists. On the one hand, Liriope plants contain much more Meanwhile, different extracts of L. platyphylla, including 25(S)-ruscogenin compounds than O. japonicas in trems of methanol, ethanol and aqueous extracts, have been tested on number and contents. On the other hand, more furostanol hematology and innate immune response in olive flounder, saponins could be found in O. japonicus. What is more, dios- Paralichthys olivaceus [79]. All of these extracts could en- genin-type saponins have been only reported to exist in O. hance the leucocytes activities against Flexibacter maritimus. japonicus so far. Cardiovascular activities Second, great efforts have been devoted to exploring the Extracts of Liriope plants have been shown to have ob- activities of crude extracts. However, only limited compounds vious cardiovascular effects, mainly by inhibiting platelet from Liriope plants have been tested in pharmacological aggregation [35], anti-myocardial ischemia [80], anti-arrhythmia studies, such as DT-13, Op-B, etc [24, 47]. High structural simi- [81], anti-ischemic [82] and anti-hypertensive activities [83]. larity, low contents as well as absence of overwhelming pro- Water-alcohol extract of L. spicata has been investigated duction in Liriope plants have made the isolation, purification in normal rats to confirm its anti-arrhythmia effects [81]. The and stereochemistry determination challenging, resulting in results have demonstrated that it might improve chloroform difficulties to obtain enough amounts for pharmacological epinephrine-induced, aconitine-induced and BaCl2-induced assays, especially for in vivo testing. This is probably one of arrhythmia at a dose of 2.5 g·kg–1 with no effect on oua- the major reasons that most of the bio-prospective experi- bain-induced arrhythmia rats [84]. The total saponins extract of ments of isolated compounds have been conducted only in Liriope plants could reduce brain infracted area and prolong vitro. For Liriope steroidal saponins, to take full advantage of the bleeding time and clotting time [82]. Besides, Compounds their anti-tumor effects, great efforts should be made in chem-

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chemistry including synthesis, structural modification, and dwarf lilyturf () [J]. Chin Tradit Herbal pharmacological studies. Most studies have concentrated on Dru, 1995, 26(4): 205-210. the pharmacodynamics with few researches at molecular level [10] Xiao PG. Modern Chinese Materia Medica [M]. Beijing: though the synergy mode of “multi-component, multi-target” Chemical Industry Press, 2002: 77-81. had already become a hotspot of traditional medicines [80]. [11] Jiangsu New Medical College. Dictionary of Chinese Herbal Medicines [M]. Shanghai: Science and Technology Press, 1986: Third, over the past few decades, it has been generally 2082. known that homoisoflavonoids could be used to distinguish [12] Jiangsu New Medical College. Encyclopedia of Chinese Me- [90-92] Liriope plants from Ophiopogon . But as we have sum- dicinal Substances [M]. Shanghai: People’s Publisher, 1986: marized, a few homoflavonoids have been identified from 2082. [34-37] Liriope plants . For a rigorous academic attitude, we [13] Wang W. Studies on the Chemical Constituents of Liriope took a rather skeptical attitude to the reports. On the one hand, graminifolia (L.) Baker [D]. Zhejing Gongshang University, the raw material used in the experiments might be much more 2010. than ever before, or they were randomly mixed with the other [14] Hur J, Lee P, Kim J, et al. Induction of nerve growth factor by folk medicines such as O. japonicus. On the other hand, with butanol fraction of Liriope platyphylla in C6 and primary as- trocyte cells [J]. Bio Pharm Bull, 2004, 27(8): 1257-1260. the rapid development of extractive and analytical technolo- [15] Lee YC, Lee JC, Seo YB, et al. Liriopis tuber inhibit OVA- gies, the existence of homoisoflavonids in Liriope plants as induced airway inflammation and bronchial hyperrespon- well as its chemotaxonomic significance will be revealed. siveness in murine model of asthma [J]. J Ethnopharmacol, Overall, Liriope emerges as a treasure of the folk medi- 2005, 101(1-3): 144-152. cines in China and other Asian countries. Owing to various [16] Kim SW, Chang IM, Oh KB. Inhibition of the bacterial surface traditional uses and extensive therapeutic applications, it protein anchoring transpeptidase sortase by medicinal plays an important role for the indigenous health care. plants [J]. Biosci Biotech Bioch, 2014, 66(12): 2751-2754. Ethno-pharmacological, phytochemical and molecular phar- [17] Yu XW, Du HZ, Sun L, et al. Research progress on the phar- macological studies have revealed a variety of biological macological effects of ophiopogonins [J]. Prog Pharm Sci, 2014, 38(4): 279-284. activities and pharmacological effects. These results provide [18] Watanabe Y, Sanada S, Ida Y, et al. Comparative studies on the remarkable evidences for the traditional application of Liriope constituents of Ophiopogonis tuber and its congeners. I. Stud- plants. With the ever increasing interest in traditional medi- ies of the constituents of the subterranean part of Liriope cines and botanical drugs worldwide, Liriope plants will cap- platyphylla Wang et Tang [J]. Chem Pharm Bull, 1983, 31(6): ture more and more attentions among chemists and pharma- 1980-1990. cologistsin the near future. [19] Yu BY, Hirai Y, Shoji J, et al. Comparative studies on the con- stituents of Ophiopogonis tuber and its congeners. VI. Studies References on the constituents of the subterranean part of var. prolifera and L. muscari [J]. Chem Pharm Bull, 1990, [1] Jiang T, Qin LP. Research on the chemical constituents and 38(7): 1931-1935. pharmacological activities of Liriope Lour [J]. J Chin Integr [20] Yu BY, Xu GJ. Simultaneous determination of glycoside B and Med, 2007, 5(4): 465-469. glycoside J in the tuberous roots of Liriope spicata by HPLC [J]. [2] Liu JF, Hong W, Zheng SQ, et al. Advances in the studies and J Chin Pharm Univ, 1991, 22(2): 114-116. developments of the resources of Liriope Lour [J]. Subtrop Ag- [21] Liu W, Wang ZL, Liang HQ. Studies on the chemical constitu- ric Res, 2008, 4(1): 9-14. ents of Liriope spicata Lour (Thunb.) var. prolifrera Y. T. MA [J]. [3] Committee of Flora of China. Flora of China [M]. Vol. 15. Acta Pharm Sin, 1989, 24(10): 749-754. Beijing: Science Press, 1978: 123-130. [22] Jae CD, Yong KS, Kun HS. Further spirostanol glycosides [4] Yang WS, Chen JC. Research and Prospect of Hubei Maidong [J]. from the tuber of Liriope Spicata [J]. Pharmacogn Mag, 1991, Lishizhen Med Mater Med Res, 2006, 17(10): 1939-1940. 22(2): 73-77. [5] Hwang DY. Enormous potential for development Liriope [23] Wang KW, Ju XY, Zhang L, et al. A novel C27-steroidal gly- platyphylla Wang et Tang as a therapeutic drug on the Human coside sulfate from Liriope graminifolia [J]. Acta Pharm Sin, chronic disease [J]. Acta Psychol, 2016, 165: 1-8. 2012, 47(5): 619-623. [6] Jeong S, Chae K, Jung YS, et al. The Korean traditional medi- [24] Qi J, Hu ZF, Zhou YF, et al. Steroidal sapogenins and gly- cine Gyeongshingangjeehwan inhibits obesity through the cosides from the fibrous roots of Ophiopogon japonicus and regulation of leptin and PPARα action in OLETF rats [J]. J Liriope spicata var. prolifera with anti-inflammatory activity [J]. Ethnopharmacol, 2008, 119(2): 245-251. Chem Pharm Bull, 2015, 63(3): 187-194. [7] Liu YH, Wan LS, Xiao ZQ, et al. Antidiabetic activity of poly- [25] Yu BY, Qiu SX, Zaw K, et al. Steroidal glycosides from the saccharides from tuberous root of Liriope spicata var. prolifera subterranean parts of Liriope spicata var. prolifera [J]. Phyto- in KKAy mice [J]. Evid-based Compl Alt, 2013, 2013(2): chemistry, 1996, 43(1): 201-206. 349790. [26] Wang KW, Zhang H, Shen LQ, et al. Novel steroidal saponins [8] Hur J, Lee P, Moon E, et al. Neurite outgrowth induced by from Liriope graminifolia (Linn.) Baker with anti-tumor ac- spicatoside A, a steroidal saponin, via the tyrosine kinase A re- tivities [J]. Carbohyd Res, 2011, 346(2): 253-258. ceptor pathway [J]. Eur J Pharmacol, 2009, 620(1-3): 9-15. [27] Cheng ZH, Wu T, Yu BY, et al. Study on the chemical con- [9] Yu BY, Xu GJ. Studies on resource utilization of Chinese drug stituents of [J]. China Tradit Herb Drugs,

– 813 – SHANG Zhan-Peng, et al. / Chin J Nat Med, 2017, 15(11): 801815

2005, 36(6): 823-826. genin 1-O-[β-D-glucopyranosyl(1→2)][β-D-xylopyra- nosyl [28] Li YW, Qi J, Zhang W, et al. Determination and fingerprint (1→3)]-β-D-fucopyranoside from tuberous roots of Liriope analysis of steroidal saponins in roots of Liriope muscari muscari (Decne.) Bailey [J]. J China Pharm Univ, 1994, 25(5): (Decne.) L. H. Bailey by ultra-high performance liquid chro- 286-288. matography coupled with ion trap time-of-flight mass spec- [47] Zhang YY, Liu JH, Kou JP, et al. DT-13, a steroidal saponin trometry [J]. J Sep Sci, 2014, 37(14): 1762-1772. from Liriope muscari L. H. Bailey, suppresses A549 cells ad- [29] Lee DY, Son KH, Do JC, et al. Two new steroidal saponins hesion and invasion by inhibiting MMP-2/9 [J]. Chin J Nat from the tubers of Liriope spicata [J]. Arch Pharm Res, 1989, Med, 2012, 10(6): 436-440. 12(4): 295-299. [48] Wang HC, Wu CC, Cheng TS, et al. Active constituents from [30] Li YW, Qi J, Zhang YY, et al. Novel cytotoxic steroidal gly- Liriope platyphylla root against cancer growth in vitro [J]. cosides from the roots of Liriope muscari [J]. Chin J Nat Med, Evid-based Compl Alt, 2013, 2013(20): 857929-857929. 2015, 13(6): 461-466. [49] Zhang YY, Ning HR, Qi J, et al. Advances in the research on [31] Cheng ZH, Wu T, Guo YL, et al. Two new steroidal glycosides DT-13, a saponin of Liriope muscari (Decne) Baily [J]. J China from Liriope muscari [J]. Chinese Chem Lett, 2006, 17(1): Pharm Univ, 2014, 45(5): 593-598. 31-34. [50] Chen MJ, Du YH, Qui M, et al. Ophiopogonin B-induced [32] Do JC, Jung KY, Yong KS, et al. Spicatoside C, a new steroidal autophagy in non-small cell lung cancer cells via inhibition of saponin from the tubers of Liriope spicata [J]. J Nat Prod, the PI3K/Akt signaling pathway [J]. Oncol Rep, 2013, 29(2): 1995, 58(5): 778-781. 430-436. [33] Choi SJ, Choi J, Jeon H, et al. Application of high-performance [51] Dong H, Zhang TP, Li J, et al. The study on inhibition of tu- countercurrent chromatography for the isolation of steroidal mour cells with sitosterol from hawthorn fruits [J]. Chin J saponins from Liriope plathyphylla [J]. J Sep Sci, 2015, 38(1): Biochem Pharm, 2009, 30(4): 270-272. 18-24. [52] Jea CD, Sung YK, Son KH. Spirostanol glycosides from the [34] Li WJ, Cheng XL, Liu J. Phenolic compounds and antioxidant tuber of Liriope spicata [J]. J Pharmacogn, 1991, 22(2): 73-77. activities of Liriope muscari [J]. Molecules, 2012, 17(2): [53] Li N, Zhang L, Zeng KW, et al. Cytotoxic steroidal saponins 1797-1808. from Ophiopogon japonicas [J]. Steroids, 2013, 78(1): 1-7. [35] Tsai YC, Chiang SY, Shazly M, et al. The oestrogenic and [54] Liu X. Study on Good Agricultural Practices of Liriope spicata anti-platelet activities of dihydrobenzofuroisocoumarins and var. prolifera and the Hypoglycemic Effect of Its Extract [D]. homoisoflavonoids from Liriope platyphylla roots [J]. Food Hubei University of Traditional Chinese Medicine, 2009. Chem, 2013, 140(1-2): 305-314. [55] Choi SB, Wha JD, Park S. The insulin sensitizing effect of [36] Wu Y, Li YW, Qi J, et al. Ethyl acetate-soluble chemical con- homoisoflavone-enriched fraction in Liriope platyphylla Wang stituents of fibrous roots of Liriope muscari [J]. Chin J Exp et Tang via PI3-kinase pathway [J]. Life Sci, 2004, 75(22): Traditl Medl Form, 2014, 20(1): 40-43. 2653-2664. [37] Tsai YC, Hsu CC, El-Shazly M, et al. Phytochemicals and [56] Chen XH, Liu YH, Bai X, et al. Hypoglycemic polysaccha- estrogen-receptor agonists from the aerial parts of Liriope rides from the tuberous root of Liriope spicata [J]. J Nat Prod, platyphylla [J]. Molecules, 2015, 20(4): 6844-6855. 2009, 72(11): 1988-1992. [38] Jin HL, Choung MG. Identification and characterisation of [57] Xiao ZQ, Wang YL, Gan SR. Polysaccharides from Liriopes anthocyanins in the antioxidant activity-containing fraction of Radix ameliorates hyperglycemia via various potential mecha- Liriope platyphylla fruits [J]. Food Chem, 2011, 127(4): nisms in diabetic rats [J]. J Sci Food Agr, 2014, 94(5): 1686-1693. 975-982. [39] Hu ZF, Chen LL, Qi J, et al. Two new benzofuran derivatives [58] Lu HJ, Tzeng TF, Liou SS, et al. Polysaccharides from Lirio- with anti-inflammatory activity from Liriope spicata Var. pro- pes radix ameliorate streptozotocin-induced type I diabetic lifera [J]. Fitoterapia, 2011, 82(2): 190-192. nephropathy via regulating NF-κB and p38 MAPK signaling [40] Li WJ, Cheng XL, Liu J, et al. Two new compounds isolated pathways [J]. J Psychopharmacol, 2014, 14(1): 117- 122. from Liriope muscari. Molecules, 2012, 17(8): 8773-8781. [59] Xu Q, Wang R, Yu BY. Effects of ruscogenin fucopyranoside [41] Zhang HM, Wang GL, Bai CQ, et al. A new eudesmane ses- on the deleyed type hypersensitivity and inflammatory reaction [J]. J quiterpene glucoside from Liriope muscari fibrous roots [J]. China Pharm Univ, 1993, 24(2): 98-101. Molecules, 2011, 16(11): 9017-9024. [60] Tian YQ, Kou JP, Zhou LL, et al. Anti-inflammatory effects of [42] Cheng ZH, Wu TS, Bashall A, et al. cis-Eudesmane sesquiter- aqueous extract from radix Liriope muscari and its major ac- pene glycosides from Liriope muscari and Ophiopogon ja- tive fraction and component [J]. Chin J Nat Med, 2011, 9(3): ponicas [J]. J Nat Prod, 2004, 67(10): 1761- 1763. 222-226. [43] Jiang C, Liu ZH, Li L, et al. A new eudesmane sesquiterpene [61] Kwak MH, Kim JE, Hwang IS, et al. Quantitative evaluation glycosides from Liriope muscari [J]. J Asian Nat Prod Res, of therapeutic effect of Liriope platyphylla on phthalic anhy- 2012, 14(5): 491-495. dride-induced atopic dermatitis in IL-4/Luc/CNS-1 Tg mice [J]. [44] Jiang T, Huang BK, Zhang QY, et al. Studies on chemical J Ethnopharmacol, 2013, 148(3): 880-889. constituents of Liriope platyphylla [J]. Chin Med Mat, 2007, [62] Tang J, Qian H, Huang Q, et al. A study on the antianaphylac- 30(9): 1079-1081. tin and antiasthmatic activity of polysaccharide from ophiop- [45] Jiang T, Tang XY, Wu JS, et al. Study on chemical constituents gonis tuber [J]. Chin J Mod Appl Pharmacy, 1999, 16(2): of the root of Liriope platyphylla [J]. Chin Med Mat, 2011, 16-19. 34(10): 1537-1539. [63] Kim KS, Cho DH, Yang HJ, et al. Effects of the inhaled treat- [46] Yu BY, Yin X, Rong ZY, et al. Biological activities of rusco- ment of Liriope radix on an asthmatic mouse model [J]. Am J

– 814 – SHANG Zhan-Peng, et al. / Chin J Nat Med, 2017, 15(11): 801815

Chinese Med, 2015, 43(3): 425-441. [78] Kim HK, Lee JY, Han HS, et al. Immunomodulatory effects of [64] Liu JL, Chen T, Yu BY, et al. Ruscogenin glycoside (Lm-3) Liriope platyphylla water extract on lipopolysaccharide- acti- isolated from Liriope muscari inhibits lymphocyte adhesion to vated mouse macrophage [J]. Nutrients, 2012, 4(12): 1887- extracellular matrix [J]. J Pharm Pharmacol, 2002, 54(7): 1897. 959-965. [79] Harikrishnan R, Kim JS, Kim MC, et al. Efficacy of Liriope [65] Park SH, Lee HJ, Ryu J, et al. Effects of ophiopogonin D and platyphylla on hematology and immune response in olive spicatoside A derived from Liriope Tuber on secretion and flounder, Paralichthys olivaceus, against Flexibacter mariti- production of mucin from airway epithelial cells [J]. Phy- mus infection [J]. J World Aquacult Soc, 2012, 43(43): 259- tomedicine, 2014, 21(2): 172-176. 269. [66] Hou WC, Lu YL, Liu SY, et al. Activities of superoxide dis- [80] Wang S, Zhang Z, Lin X, et al. A polysaccharide, MDG-1, mutase and glutathione peroxidase in of different culti- induces S1P1 and bFGF expression and augments survival and vars of Liriope spicata L. on 10% SDS-PAGE gels [J]. Bot Bull angiogenesis in the ischemic heart [J]. Glycobiology, 2010, Acad Sinica, 2003, 44(1): 37-41. 20(4): 473-484. [67] Hou WC, Wu WC, Yang CY. Antioxidant activities of metha- [81] Gao GY, Han GZ, Liu YH, et al. Study on the antiarrhythmic nolic and hot-water extracts from leaves of three of effect of Radix Liriope [J]. Chin Pharm Bull, 1984, 19(12): 58. Mai-Men-Dong (Liriope spicata L.) [J]. Bot Bull Acad Sinica, [82] Deng S, Li WP, Ren KH, et al. Neurpprotective and anticoagu- 2004, 45(4): 285-290. lation effect of total saponins of radix Liriopes on focal cere- [68] Mun JH, Lee SG, Kim DH, et al. Neurotrophic factors mediate bral ischemia [J]. Chin Pharm, 2007, 18(30): 2332- 2334. memory enhancing property of ethanolic extract of Liriope [83] Lee YJ, Koh EK, Kim JE, et al. Beneficial effects of ethanol platyphylla in mice [J]. J Appl Pharmacol, 2007, 5(6): 670-674. extracts of Red Liriope platyphylla on vascular dysfunction in [69] Park HR, Lee H, Park H, et al. Neuroprotective effects of the aorta of spontaneously hypertensive rats [J]. Lab Ani Res, Liriope platyphylla extract against hydrogen peroxide-induced 2015, 31(1): 13-23. cytotoxicity in human neuroblastoma SH-SY5Y cells [J]. BMC [84] Li WP, Han XY, Gao GY, et al. Effect of oral water-soluble Complem Altern M, 2015, 15(1): 1-11. extract of Liriope Spicata Lour. (WSEL) on the experimental [70] Jiang T, Huang BK, Zhang QY, et al. Effect of Liriope platy- arrhythmia in animals [J]. J Dalian Med Univ, 1989, 11(2): phylla total saponin on learning, memory and metabolites in 62-64. aging mice induced by D-galactose [J]. Chin J Integr Med, [85] Wu FH, Cao JS, Jiang JY, et al. Ruscogenin glycoside (Lm-3) 2007, 5(6): 670-674. isolated from Liriope muscari improves liver injury by dys- [71] Kim HJ, Park SY, Kim DG. Effects of the roots of Liriope functioning liver-infltrating lymphocytes [J]. J Pharm Phar- platyphylla Wang et Tang on gastrointestinal motility function [J]. J macol, 2001, 53(5): 681-688. Ethnopharmacol, 2016, 184: 144-153. [86] Wu Y, Zhang WJ, Wang PJ, et al. Contact toxicity and repel- [72] Kim JE, Park SH, Kwak MH, et al. Characterization of lency of the essential oil of Liriope muscari (DECN.) Bailey changes in global genes expression in the distal colon of lop- against three inset tobacco storage pests [J]. Molecules, 2015, eramide-induced constipation SD rats in response to the laxa- 12:1676-1685. tive effects of Liriope platyphylla [J]. PLoS One, 2015, 10(7): [87] Li M, Wang ZC, Dai HJ, et al. Response surface optimization e0129664. of polysaccharides extraction from Liriope roots and its modu- [73] Kim JE, Lee YJ, Kwak MH, et al. Aqueous extracts of Liriope latory effect on sjogren syndrome [J]. Int J Biol Macromol, platyphylla induced significant laxative effects on loperamide- 2009, 45(3): 284-288. induced constipation of SD rats [J]. BMC Complem Altern Med, [88] Shen L, Xu DS, Feng Y, et al. Relative bioavailability of 2013, 13(6): 333. Ophiopogon japonicas saponin enteric microsphere in rats [J]. [74] Han FM, Liu CX, Chen Y. The protective effect of radix Lirio- Chin Tradit Herb Drug, 2005, 36(5): 683-686. pes polysaccharide on immunosuppressive mice [J]. Chin J [89] Guan Y, Zhong Y, Shi J, et al. Research advance on dosage Tradit Chin Med Pharm, 2004, 19(6): 347-348. forms of saponins [J]. Chin Wild Plants Res, 2013, 32(1): 15- [75] Liu YG, Xu JH, Zhang HL. Effect of Liriope muscari polysac- 17. charide on peritoneal macrophages in mice [J]. Chin Tradit Pat [90] Tang XQ, Cheng ZH, Yu BY. Qualitative and quantitative Med, 2015, 37(10): 2290-2292. studies on chinese drug maidong [J]. Chin J Chin Mater Med, [76] Liu YG, Zhang HL, Xu JH. Immunoloregulation effect of 1999, 24(7): 390-393. polysaccharides from Liriope muscari (Decne.) Baily in im- [91] Lin YN, Yu BY. Determination of total phenolic constituents of munosuppressive mice [J]. Strait Pharm J, 2015, 27(2): 13-15. Ophiopogon japonicus by chemiluminescence [J]. J Chin Med [77] Liu YG, Zhang HL. Effected on immunity function of Liriope Mater, 2006, 29(8): 797-798. muscari (Decne.) Baily polysaccharides in mice [J]. Strait [92] Yu BY, Xu GJ. Studies on resource utilization of Chinese drug [J]. Pharm J, 2014, 26(11): 31-32. Chin Tradi Herb Drug, 1995, 26(4): 205-210.

Cite this article as: SHANG Zhan-Peng, WANG Fei, ZHANG Jia-Yu, WANG Zi-Jian, LU Jian-Qiu, LI Ning. The genus Liriope: Phytochemistry and pharmacology [J]. Chin J Nat Med, 2017, 15(11): 801-815.

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