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REVIEW Chemical Constituents of Plants from the Genus Paris by Jin-Chao Wei a ) b ), Wen-Yuan Gao* a ), Xiao-Dan Yan b ), Ying Wang b ), Song-Song Jing a ), and PeiGen Xiao c ) a

) School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P. R. China (phone: þ 86-22-87401895; fax: þ 86-22-87401895; e-mail: [email protected]) b ) School of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, P. R. China c ) Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, P. R. China

1. Introduction. – The genus Paris, perennial herbs, widely distributed from Europe to Eastern Asia, comprises 24 species of the Trilliaceae family [1 – 3]. For years, some Paris species have been applied in traditional Chinese medicine for the treatment of hemostasis, snake bite, and abscess. In recent years, studies on the EtOH, H2O, and MeOH extracts of Paris polyphylla revealed antitumor activity against several types of cancer cell lines [4]. More extensive phytochemical investigations of the genus Paris have led to the identification of various compounds, such as steroid saponins, phytoecdysones, phytosterols, phenylpropanoids, flavonoids, etc. Recent pharmacological studies further identified Rhizoma Paridis saponins (RPS), which showed broad biological features, such as hypocholesterolemic, antitumor, anti-inflammatory, antifungal activities, and inhibitory activity against platelet aggregation and cAMP phospho-diesterase, as the main active components in Paris [5 – 9]. Our phytochemical investigations on six Paris species (Paris polyphylla var. yunnanensis, Paris verticillata, Paris Pubescends, Paris axialis, Paris polyphylla var. pseudothibetica, and Paris fargesii) also disclosed that steroid saponins are the main constituents of Paris, along with many other constituents, including flavonoids, phenylpropanoids, ecdysteroids, phenolic glycosides, etc. [10 – 20]. Up to now, 96 compounds including two new compounds, parispolysides F and G, were obtained from the rhizomes of six Paris species by using repeated column chromatography, and they were all elucidated and identified by means of 1H- and 13C-NMR, and of 2D-NMR spectra. Our pharmacological research showed that the components extracted from Paris polyphylla var. yunnanensis had strong antilung cancer activity [10] [11] [14]. The purified mixture isolated from RPS, mainly composed of polyphyllin D, paris H, and paris VII, exhibited a powerful antiproliferation effect by inducing apoptosis and inhibiting metastasis [21]. The biological properties assigned to to genus Paris prompted us to compile the phytochemical progress. Here, we review the phytochemical and biological research on Paris and list all the compounds isolated over the past few decades, also considering their biological activities.

 2014 Verlag Helvetica Chimica Acta AG, Zrich

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2. Chemical Constituents. – According to the literature, the phytochemical investigations on Paris have resulted in isolation and characterization of 126 constituents, 1 – 126, including steroid saponins, phytoecdysones, phytosterols, penylpropanoids, flavonoids, and others. Their structures are shown below, and their names and the corresponding plant sources are compiled in the Table. As can be seen, steroid saponins and flavonoids are the predominant constituents within the genus Paris. 2.1. Steroid Saponins. In total, 94 steroid saponins were isolated from the genus Paris. Among them, the most frequent representatives are the spirostane-type saponins, the diosgenin saponins 1 – 20. The diosgenin saponin is a hexacyclic A – F-ring system, with the oligosaccharidic group linked to the aglycon at C(3). Compound 1 was isolated for the first time from P. pubescens, and its structure and absolute configuration were elucidated by spectroscopic methods [17], and, successively, it was identified in P. polyphylla var. pseudothibetica [18] and P. axialis [19]. In a large number of diosgenin saponins, the glycosyl unit is a a-l-rhamnopyranosyl-(1 ! 2)-b-d-glucopyranoside or bd-glucopyranoside, which is further substituted in positions 2, 3, 4, and 5 by glucopyranosyl, rhamnopyranosyl, and arabinofuranosyl moieties [7 – 32]. In 2012, compound 13 with a b-d-apiofuranosyl moiety was isolated from the EtOH extract of the rhizomes of P. polyphylla var. yunnanensis. At the same time, compounds 8, 10, and 20 were found in P. polyphylla var. yunnanensis [30]. Pennogenin saponins, i.e., the diosgenins with a OH group at C(17), were isolated for the first time from the whole plants of P. verticillata by Nakano et al. in 1981 [40]. Subsequently, numerous such saponins, 21 – 26, 28, and 32, were identified in P. polyphylla var. chinensis [7] [28], P. polyphylla var. yunnanensis [10] [23] [31] [36], P. polyphylla [28], P. luquanensis [37], P. quadrifolia [39]. Recently, the pennogenin saponins with xylopyranosyl and apiofuranosyl moieties, i.e., 29, 30, and 34, were found in P. polyphylla var. yunnanensis [30] and P. polyphylla [6], respectively. Various hydroxylated compounds related to diosgenin and pennogenin saponin have been isolated from Paris species. 24-Hydroxypennogenins, 35 – 38 were found in P. axialis by Chen and Zhou in 1984 and 1987 [42] [43]. Compounds 39 and 40, the pennogenin saponins with 27-OH group, were identified in the aerial parts of P. polyphylla var. yunnanensis [44] [45], and, successively, the other 27-OH saponins 41 and 42 were isolated from the rhizomes of P. polyphylla var. yunnanensis [30]. 23,27Dihydroxy saponins 43 – 45 were obtained from P. polyphylla var. yunnanensis [44] [46] [47]. In 2007, Zhao et al. reported a pair of stereoisomeric new spirostanol saponins, 47 and 48, from the rhizomes of P. polyphylla var. yunnanensis [48]. From the same plant, Wu et al. isolated the same aglycone saponins, 46 and 49, in 2012, together with additional 16 compounds [30]. Furostanol saponins, 51 – 65, with a b-glucopyranosyl moiety at C(26) of the aglycone, were isolated from several Paris species. 17-Hydroxy and 22-MeO furostanol saponins 61 – 65, and 57 – 60 and 63 – 65, respectively, were found in P. verticillata [15] [40], P. polyphylla var. yunnanensis [23] [31], P. polyphylla [28] [50], P. quadrifolia [39], and P. axialis [42]. The furostanol saponins, with a C(20)¼C(22) bond, 66 and 67, were isolated by Zhao et al. from P. polyphylla var. yunnanensis [23]. Nuatigenin (68) and isonuatigenin (69), supposedly derivatives of pseudo-spirostanol, were also obtained from P. polyphylla var. yunnanensis [46]. Parisvietnaside A (74) was the first 5,6-dihydroxy saponin isolated from P. vietnamensis by Huang et al. [25], but the

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Table. Chemical Constituents from the Genus Paris No. Compound class and name 1

Steroid saponins Diosgenin

2

Diosgenin 3-O-b-d-glucopyranoside (trillin)

3

Diosgenin 3-O-a-l-rhamnopyranosyl(1 ! 2)-b-d-glucopyranoside (paris V )

4

Diosgenin 3-O-a-l-rhamnopyranosyl(1 ! 4)-b-d-glucopyranoside

5

Diosgenin 3-O-a-l-rhamnopyranosyl(1 ! 3)-b-d-glucopyranoside (polyphyllin C ) Diosgenin 3-O-a-l-arabinofuranosyl(1 ! 4)-b-d-glucopyranoside

6

7

8

9 10

11 12 13

Diosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)[a-l-rhamnopyranosyl-(1 ! 4)]-b-d-glucopyranoside (dioscin/parisaponin III ) Diosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)[a-l-arabinofuranosyl-(1 ! 4)]-b-d-glucopyranoside (polyphyllin D )

Diosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)[a-l-arabinofuranosyl-(1 ! 3)]-b-d-glucopyranoside Diosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)[b-d-glucopyranosyl-(1 ! 3)]-b-d-glucopyranoside (gracillin)

Diosgenin 3-O-a-l-arabinofuranosyl-(1 ! 4)[a-l-rhamnopyranosyl-(1 ! 3)]-b-d-glucopyranoside Diosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 4)[a-l-arabinofuranosyl-(1 ! 3)]-b-d-glucopyranoside Diosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)[b-d-apiofuranosyl-(1 ! 3)]-b-d-glucopyranoside

Source

Ref.

P. pubescens P. pseudothibetica P. axialis P. yunnanensis P. polyphylla P. chinensis P. axialis P. fargesii P. yunnanensis P. delavayi P. vietnamensis P. yunnanensis P. polyphylla P. chinensis P. vietnamensis P. polyphylla P. axialis P. pubescens P. yunnanensis P. vietnamensis P. polyphylla P. yunnanensis P. pubescens P. mairei P. chinensis P. yunnanensis P. verticillata p. pubescens P. pseudothibetica P. axialis P. fargesii P. delavayi P. vietnamensis P. polyphylla P. mairei P. chinensis

[17] [18] [19] [10] [22] [7] [19] [20] [10] [23] [24] [25] [10] [22] [26] [25] [27] [16] [17] [23] [25] [28] [10] [17] [29] [7] [8] [23] [30] [15] [17] [18] [19] [20] [24] [25] [28] [29] [26]

P. chinensis P. yunnanensis P. delavayi P. vietnamensis P. polyphylla

[7] [23] [30] [31] [24] [25] [27]

P. yunnanensis

[32]

P. yunnanensis

[30]

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Table (cont.) No. Compound class and name 14

Diosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)[a-l-rhamnopyranosyl-(1 ! 4)-a-l-rhamnopyranosyl(1 ! 4)]-b-d-glucopyranoside (Pb/formosanin C )

15

Diosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 4)[a-l-rhamnopyranosyl-(1 ! 3)]-[b-d-glucopyranosyl(1 ! 2)]-a-l-rhamnopyranoside (polyphyllin F ) Diosgenin 3-O-b-d-glucopyranosyl-(1 ! 3)a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 3)]-b-d-glucopyranoside (pariphyllin A) Diosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 5)a-l-arabinofuranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside Diosgenin 3-O-b-d-glucopyranosyl-(1 ! 5)a-l-arabinofuranosl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside Diosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 3)]-b-d-glucopyranoside (polyphyllin E ) Diosgenin 3-O-b-d-glucopyranosyl-(1 ! 4)a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside Pennogenin 3-O-b-d-glucopyranoside Pennogenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)b-d-glucopyranoside (paris VI)

16

17

18

19

20

21 22

23 24

25

Pennogenin 3-O-a-l-rhamnopyranosyl-(1 ! 4)b-d-glucopyranoside Pennogenin 3-O-a-l-arabinofuranosyl-(1 ! 4)b-d-glucopyranoside

Pennogenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)-[a-larabinofuranosyl-(1 ! 4)]-b-d-glucopyranoside (paris H)

Source

Ref.

P. chinensis P. yunnanensis P. pubescens P. axialis P. fargesii P. delavayi P. vietnamensis P. polyphylla P. formosana P. polyphylla

[7] [8] [23] [17] [19] [20] [24] [25] [28] [33] [27]

P. yunnanensis P. polyphylla

[31] [34]

P. fargesii P. yunnanensis

[20] [23]

P. yunnanensis

[23]

P. polyphylla

[27]

P. yunnanensis

[30]

P. chinensis P. chinensis P. yunnanensis P. pubescens P. axialis P. fargesii P. vietnamensis P. delavayi P. yunnanensis P. verticillata P. chinensis P. yunnanensis P. pubescens P. pseudothibetica P. vietnamensis P. polyphylla P. delavayi P. chinensis P. yunnanensis P. verticillata P. pubescens P. pseudothibetica

[7] [7] [10] [23] [17] [19] [20] [25] [35] [10] [36] [15] [7] [10] [23] [30] [17] [18] [25] [28] [35] [7] [8] [10] [23] [15] [17] [18]

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Table (cont.) No. Compound class and name

26

Pennogenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)[b-d-glucopyranosyl-(1 ! 3)]-b-d-glucopyranoside

27

Pennogenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)[a-l-rhamnopyranosyl-(1 ! 4)]-b-d-glucopyranoside Pennogenin 3-O-a-l-rhamnopyranosyl-(1 ! 4)a-l-rhamnopyranosyl-(1 ! 4)-b-d-glucopyranoside Pennogenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)[b-d-apiofuranosyl-(1 ! 3)]-b-d-glucopyranoside Pennogenin 3-O-b-d-xylopyranosyl-(1 ! 5)a-l-arabinofuranosyl-(1 ! 4)-b-d-glucopyranoside Pennogenin 3-O-b-d-glucopyranosyl-(1 ! 5)a-l-arabinofuranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside Pennogenin 3-O-a-l-rhamnopyranosyl-(1 ! 4)a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside (paris VII/Tg)

28 29 30 31

32

33

34

35 36 37

38 39

Pennogenin 3-O-a-l-rhamnopyranosyl-(1 ! 4)a-l-rhamnopyranosyl-(1 ! 3)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside Pennogenin 3-O-a-l-rhamnopyranosyl-(1 ! 2)[b-d-xylopyranosyl-(1 ! 5)-a-l-arabinofuranosyl(1 ! 4)]-b-d-glucopyranoside 24a-Hydroxypennogenin 3-O-a-l-rhamnopyranosyl(1 ! 2)-[a-l-rhamnopyranosyl-(1 ! 3)]-b-d-glucopyranoside 24a-Hydroxypennogenin 3-O-a-l-rhamnopyranosyl(1 ! 2)-[a-l-arabinofuranosyl-(1 ! 4)]-b-d-glucopyranoside 24a-Hydroxypennogenin 3-O-a-l-rhamnopyranosyl(1 ! 4)-a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside 24a-Hydroxypennogenin 3-O-a-l-rhamnopyranosyl(1 ! 2)-[b-d-glucopyranosyl-(1 ! 3)]-b-d-glucopyranoside 27-Hydroxypennogenin

Source

Ref.

P. axialis P. fargesii P. delavayi P. vietnamensis P. polyphylla P. luquanensis P. chinensis P. yunnanensis P. vietnamensis P. yunnanensis P. quadrifolia P. chinensis P. yunnanensis P. yunnanensis

[19] [20] [24] [25] [28] [37] [7] [23] [25] [38] [39] [7] [30] [30]

P. yunnanensis

[30]

P. yunnanensis

[30]

P. chinensis P. verticillata P. pubescens P. pseudothibetica P. axialis P. fargesii P. yunnanensis P. delavayi P. vietnamensis P. polyphylla P. luquanensis P. quadrifolia P. yunnanensis

[7] [15] [40] [17] [18] [41] [19] [20] [23] [30] [31] [24] [25] [28] [37] [39] [32]

P. polyphylla

[6]

P. axialis

[42]

P. axialis

[42]

P. axialis

[42]

P. axialis

[43]

P. yunnanensis

[44]

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Table (cont.) No. Compound class and name 40

41 42

43 44

45 46 47

48

49 50

51 52

53

54

55

56

57

27-Hydroxypennogenin 3-O-a-l-rhamnopyranosyl(1 ! 4)-a-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside (polyphylloside III) 27-Hydroxypennogenin 3-O-a-l-arabinofuranosyl(1 ! 4)-b-d-glucopyranoside 27-Hydroxydiosgenin 3-O-a-l-rhamnopyranosyl-(1 ! 4)a-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]b-d-glucopyranoside 23,27-Dihydroxypennogenin 23,27-Dihydroxypennogenin 3-O-a-l-rhamnopyranosyl(1 ! 4)-a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside (polyphylloside IV ) (23S,25S )-3b,23,27-Trihydroxyspirost-5-ene 3-O-b-dglucopyranosyl-(1 ! 6)-b-d-glucopyranoside (25R )-Spirost-5-ene 3b,7a-diol-3-O-a-l-arabinofuranosyl(1 ! 4)-b-d-glucopyranoside (25R )-3b,7a-Dihydroxispirost-5-ene 3-O-a-l-arabinofuranosyl(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranoside (parisyunnanoside D ) (25R )-3b,7b-Dihydroxispirost-5-ene 3-O-a-l-arabinofuranosyl(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranoside (parisyunnanoside E ) (25R )-3b,7b-Dihydroxispirost-5-ene 3-O-b-d-glucopyranosyl(1 ! 3)-[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranoside (25R )-3b,12a-Dihydroxispirost-5-ene 3-O-a-l-rhamnopyranosyl(1 ! 4)-a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside (parisyunnanoside C) (25R )-26-O-b-d-Glucopyranosyl-3b,22,26-trihydroxyfurost5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 2)-b-d-glucopyranoside (25R )-26-O-b-d-Glucopyranosyl-3b,22,26-trihydroxyfurost5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 2)-[a-l-arabinofuranosyl(1 ! 4)]-b-d-glucopyranoside (parisaponin I ) (25R )-26-O-b-d-Glucopyranosyl-3b,22,26-trihydroxyfurost5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 2)-[b-d-glucopyranosyl(1 ! 3)]-b-d-glucopyranoside (protogracillin) (25R )-26-O-b-d-Glucopyranosyl-3b,22,26-trihydroxyfurost5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 2)[a-l-arabinofuranosyl-(1 ! 3)]-b-d-glucopyranoside (25R )-26-O-b-d-Glucopyranosyl-3b,22,26-trihydroxyfurost5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 3)-[a-l-arabinofuranosyl(1 ! 4)]-b-d-glucopyranoside (polyphyllin G ) (25R )-26-O-b-d-Glucopyranosyl-3b,22,26-trihydroxyfurost5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 4)-a-l-rhamnopyranosyl(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranoside (dichotomin) (25R )-26-O-b-d-Glucopyranosyl-3b,26-dihydroxy-22methoxyfurost-5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 3)[a-l-arabinofuranosyl-(1 ! 4)]-b-d-glucopyranoside

Source

Ref.

P. yunnanensis

[45]

P. yunnanensis

[30]

P. yunnanensis

[30]

P. yunnanensis P. yunnanensis

[44] [46]

P. yunnanensis

[47]

P. yunnanensis

[30]

P. yunnanensis

[48]

P. yunnanensis

[48]

P. yunnanensis

[30]

P. yunnanensis

[23]

P. yunnanensis

[8] [32]

P. yunnanensis

[8] [23] [49]

P. yunnanensis

[8] [23]

P. yunnanensis

[32]

P. polyphylla

[50]

P. yunnanensis

[23]

P. polyphylla

[50]

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Table (cont.) No. Compound class and name 58

59

60

61

62

63

64

65

66

67

68

69

70 71

72

(25R )-26-O-b-d-Glucopyranosyl-3b,26-dihydroxy-22methoxyfurost-5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 2)[b-d-glucopyranosyl-(1 ! 3)]-b-d-glucopyranoside (methyl protoneogracillin) (25R )-26-O-b-d-Glucopyranosyl-3b,26-dihydroxy-22methoxyfurost-5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 2)[a-l-rhamnopyranosyl-(1 ! 4)-a-l-rhamnopyranosyl-(1 ! 4)]b-d-glucopyranoside (25R )-26-O-b-d-Glucopyranosyl-3b,26-dihydroxy-22-methoxyfurost-5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 2)-[a-l-arabinofuranosyl-(1 ! 4)]-b-d-glucopyranoside (polyphyllin H ) (25R )-26-O-b-d-Glucopyranosyl-3b,17a,22a,26-tetrahydroxyfurost-5-ene 3-O-a-l-arabinofuranosyl-(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranoside (parisyunnanoside A ) (25R )-26-O-b-d-Glucopyranosyl-3b,17a,22a,26-tetrahydroxyfurost-5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 4)-a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]b-d-glucopyranoside ( Th) (25R )-26-O-b-d-Glucopyranosyl-3b,26-dihydroxy-22-methoxyfurost-5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 2)-[a-l-arabinofuranosyl-(1 ! 4)]-b-d-glucopyranoside (25R )-26-O-b-d-Glucopyranosyl-3b,26-dihydroxy-22methoxyfurost-5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 2)[b-d-gluco-pyranosyl-(1 ! 3)]-b-d-glucopyranoside (25R )-26-O-b-d-Glucopyranosyl-3b,26-dihydroxy-22-methoxyfurost-5-ene 3-O-a-l-rhamnopyranosyl-(1 ! 2)-[a-l-rhamnopyranosyl-(1 ! 4)-a-l-rhamnopyranosyl-(1 ! 4)]-b-d-glucopyranoside (25R )-26-O-b-d-Glucopyranosyl-3b,26-dihydroxyfurosta5,20(22)-diene 3-O-a-l-rhamnopyranosyl-(1 ! 4)a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranoside (25R )-26-O-b-d-Glucopyranosyl-3b,26-dihydroxyfurost5,20(22)-diene 3-O-a-l-arabinofuranosyl-(1 ! 4)[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranoside (parisyunnanoside B ) 26-O-b-d-Glucopyranosylnuatigenin 3-O-a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]b-d-glucopyranoside (nuatigenin) Isonuatigenin 3-O-a-l-rhamnopyranosyl-(1 ! 4)[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranoside (isonuatigenin) (3b,5a,6b,25R )-3,5,6-Trihydroxyspirostane 3-O-a-lrhamnopyranosyl-(1 ! 2)-b-d-glucopyranoside (3b,5a,6b,25R )-3,5,6-Trihydroxyspirostane 3-O-b-dapiofuranosyl-(1 ! 3)-[a-l-rhamnopyranosyl-(1 ! 2)]b-d-glucopyranoside (25R )-3b,5a,6b-Trihydroxyspirost-7-ene 3-O-b-dglucopyranosyl-(1 ! 3)-[a-l-rhamnopyranosyl-(1 ! 2)]b-d-glucopyranoside

Source

Ref.

P. axialis

[43]

P. polyphylla

[28]

P. polyphylla

[28]

P. yunnanensis

[23] [31]

P. yunnanensis P. verticillata P. quadrifolia

[23] [15] [39]

P. axialis

[42]

P. axialis

[42]

P. verticillata

[40]

P. yunnanensis

[23]

P. yunnanensis

[23]

P. yunnanensis

[46]

P. yunnanensis

[46]

P. yunnanensis

[30]

P. yunnanensis

[30]

P. yunnanensis

[49]

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Table (cont.) No. Compound class and name 73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

3b,5a,6a-Trihydroxyisospirost-7-ene 3-O-a-l-rhamnopyranosyl-(1 ! 4)-a-l-rhamnopyranosyl-(1 ! 4)[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranoside 3b,5a,6a-Trihydroxyisospirost-7-ene 3-O-b-d-glucopyranosyl-(1 ! 3)-[a-l-rhamnopyranosyl-(1 ! 2)]b-d-glucopyranoside (parisvietnaside A) 16b-{[(5-O-(b-d-Glucopyranosyloxy)-4-methylpentanoyl]oxy}-3b-hydroxy-20-oxopregn-5-en 3-O-a-lrhamnopyranosyl-(1 ! 2)-[a-l-rhamnopyranosyl-(1 ! 4)]b-d-glucopyranoside (hypoglaucin G ) 3-Hydroxy-20-oxopregna-5,16-diene 3-O-a-l-rhamnopyranosyl-(1 ! 2)-[a-l-rhamnopyranosyl-(1 ! 4)]b-d-glucopyranoside 3-Hydroxy-20-oxopregna-5,16-diene 3-O-a-l-rhamnopyranosyl-(1 ! 2)-[a-l-arabinofuranosyl-(1 ! 4)]b-d-glucopyranoside 3-Hydroxy-20-oxopregna-5,16-diene 3-O-a-l-rhamnopyranosyl-(1 ! 2)-[a-l-rhamnopyranosyl-(1 ! 4)-a-lrhamnopyranosyl-(1 ! 4)]-b-d-glucopyranoside (20S )-3,21-Dihydroxypregn-5-ene-22,16-lactone 1-O-a-l-rhamnopyranosyl-(1 ! 2)-[b-d-xylopyranosyl(1 ! 3)]-b-d-glucopyranoside (20R )-21-O-b-d-Galactopyranosyl-1b,3b,21-trihydroxypregn-5-ene-20,16b-lactone 1-O-a-l-rhamnopyranosyl(1 ! 2)-[b-d-xylopyranosyl-(1 ! 3)]-b-d-glucopyranoside (parisyunnanoside J ) 3-O-[a-l-Rhamnopyranosyl-(1 ! 2)-b-d-glucopyranosyl]homoarocholest-5-ene 26-O-b-d-glucopyranoside (parispseudoside B) 3-O-{a-l-Arabinofuranosyl-(1 ! 4)-[a-l-rhamnopyranosyl(1 ! 2)]-b-d-glucopyranosyl}homoarocholest-5-ene26-O-b-d-glucopyranoside (parispolyside E ) 3-O-{a-l-Rhamnopyranosyl-(1 ! 4)-a-l-rhamnopyranosyl(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranosyl}homoarocholest-5-ene 26-O-b-d-glucopyranoside (parispseudoside A) (23S,24S )-24-O-b-d-Galactopylanosyl-1b,3b,23,24hydroxyspirosta-5,25(27)-diene 1-O-b-d-xylopyranosyl-(1 ! 6)b-d-glucopyranosyl-(1 ! 3)-[a-l-rhamnopyranosyl-(1 ! 2)]b-d-glucopyranoside (23S,24S )-24-O-b-d-Fucopyranosyl-21-O-b-d-galactopyranosyl-1b,3b,21,23,24-pentahydroxyspirosta-5,25(27)diene 1-O-a-l-rhamnopyranosyl-(1 ! 2)-[b-d-xylopyranosyl(1 ! 3)]-b-d-glucopyranoside (parisyunnanoside I) (23S,24S )-24-O-b-d-Fucopyranosyl-21-O-b-d-galactopylanosyl-1b,3b,21,23a,24a-pentahydroxyspirosta-5,25diene 1-O-a-l-rhamnopyranosyl-(1 ! 2)-[b-d-xylopyranosyl-(1 ! 3)]-b-d-glucopyranoside (parisyunnanoside G ) (23S,24S )-24-O-b-d-Fucopyranosyl-1b,3b,21,23a,24apentahydroxyspirosta-5,25-diene 1-O-a-l-rhamnopyranosyl-

Source

Ref.

P. yunnanensis

[23]

P. vietnamensis

[25]

P. mairei

[29]

P. yunnanensis

[38]

P. polyphylla

[22]

P. yunnanensis

[38]

P. chinensis

[51]

P. yunnanensis

[52]

P. pseudothibetica [41]

P. pseudothibetica [41] P. chinensis [51] [53] P. pseudothibetica [41]

P. yunnanensis

[31]

P. yunnanensis

[52]

P. yunnanensis

[52]

P. yunnanensis

[52]

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Table (cont.) No. Compound class and name

88

89

90

91

92 93 94

(1 ! 2)-[b-d-xylopyranosyl-(1 ! 3)]-b-d-glucopyranoside (parisyunnanoside H ) (23S,24S,25S )-24-O-b-l-Fucopyranosyl-1b,3b,21,23,24pentahydroxyspirost-5-ene 1-O-a-l-rhamnopyranosyl-(1 ! 2)[b-d-xylopyranosyl-(1 ! 3)]-b-d-glucopyranoside (padelaoside A ) (23S,24S,25S )-24-O-b-d-Fucopyranosyl-1b,3b,21,23,24pentahydroxyspirost-5-ene 1-O-a-l-rhamnopyranosyl(1 ! 2)-[b-d-xylopyranosyl-(1 ! 3)]-b-d-glucopyranoside (padelaoside B ) (25R )-26-O-b-d-Glucopyranosyl-3b,26-hydroxy-16,22dioxocholesta-5,17(20)-diene 3-O-a-l-arabinofuranosyl(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranoside (parispolyside F ) (25R )-26-O-b-d-Glucopyranosyl-16,22-dioxocholesta5,17(20)-diene 3-O-a-l-Rhamnopyranosyl-(1 ! 4)a-l-rhamnopyranosyl-(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]b-d-glucopyranoside (parispseudoside C) 1-Dehydrotrillenogenin (3b,25R)-3-Hydroxy-7-oxospirost-5-ene a-lrhamnopyranosyl-(1 ! 2)-b-d-glucopyranoside (3b,25R)-3-Hydroxy-7-oxospirost-5-ene a-l-arabino-furanosyl(1 ! 4)-[a-l-rhamnopyranosyl-(1 ! 2)]-b-d-glucopyranoside

Flavonoids 95 Kaempferol 96 Kaempferol 3-O-a-l-rhamnopyranosyl-(1 ! 2)b-d-glucopyranoside 97 Kaempferol 3-O-b-d-glucopyranosyl-(1 ! 6)b-d-glucopyranoside 98 7-O-a-l-Rhamnopyranosylkaempferol 3-O-a-lglucopyranosyl-(1 ! 6)-b-d-glucopyranoside 99 7-O-b-d-Glucopyranosylkaempferol 3-O-a-lrhamnopyranosyl-(1 ! 2)-b-d-glucopyranoside 100 Isorhamnetin 3-O-b-d-glucopyranoside 101 Isorhamnetin 3-O-b-d-glucopyranosyl(1 ! 6)-b-d-glucopyranoside 102 Isorhamnetin 3-O-a-l-rhamnopyranosyl(1 ! 2)-b-d-glucopyranoside 103 Quercetin 104 Quercetin 3-O-b-d-galactopyranoside 105 Rutin 106 Luteolin 107 Luteoloside 108 Naringenin 109 Myricetin 110 4,2’,4’-Trihydroxychalcone 111 Amentoflavone 112 Kayaflavone

Source

Ref.

P. mairei P. delavayi

[29] [35]

P. delavayi

[35]

P. pseudothibetica [41] P. yunnanensis [48]

P. pseudothibetica [41]

P. quadrifolia P. yunnanensis

[39] [30]

P. yunnanensis

[30]

P. axialis P. pseudothibetica P. verticillata P. yunnanensis P. quadrifolia

[16] [18] [40] [45] [39]

P. yunnanensis

[45]

P. verticillata

[40]

P. axialis P. yunnanensis P. axialis P. yunnanensis P. axialis P. axialis P. axialis P. axialis P. axialis P. axialis P. axialis P. axialis P. axialis P. axialis P. axialis

[16] [13] [16] [13] [19] [16] [16] [16] [19] [19] [16] [16] [16] [16] [16]

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Table (cont.) No. Compound class and name Phytoecdysones 113 b-Ecdysone (20-hydroxyecdysone)

114 115 116 117

Pinnatasterone a-Ecdysone Paristerone Ajugasterone

Phytosterols 118 b-Sitosterol

119 Daucosterol

120 Stigmasterol

121 Stigmasterol 3-O-b-d-glucopyranoside Phenylpropanoids 122 Parispolyside F 123 3,6-Di-O-feruloyl-b-d-fructofuranosyl a-d-glucopyranoside (helonioside A ) 124 Parispolyside G Others 125 (2S,3S,4E,8E )-1-O-b-d-Glucopyranosyl-2-{[(2R )2-hydroxyhexadecanoyl]amino}octadeca-4,8-diene-1,3-diol 126 Ethyl a-d-fructofuranoside

Source

Ref.

P. yunnanensis P. verticillata P. axialis P. pubescens P. pseudothibetica P. fargesii P. delavayi P. formosana P. luquanensis P. yunnanensis P. verticillata P. polyphylla P. verticillata

[10] [15] [40] [16] [17] [18] [20] [24] [32] [37] [52] [40] [54] [40]

P. pseudothibetica P. fargesii P. verticillata P. axialis P. pseudothibetica P. delavayi P. luquanensis P. verticillata P. pubescens P. pseudothibetica P. verticillata P. axialis P. pseudothibetica

[18] [20] [40] [16] [18] [24] [37] [40] [17] [18] [40] [16] [18]

P. yunnanensis P. yunnanensis

[13] [14]

P. yunnanensis

[13]

P. yunnanensis

[12]

P. yunnanensis

[11]

structure of the compound was revised later by Liu et al. [49], who corrected the configuration of the 6-OH group from a to b. Three pregane-type derivatives, 76 – 78, were isolated from P. polyphylla [22] and P. polyphylla var. yunnanensis [38]. Three compounds with homo-aro-cholestane skeletons, 81 – 83, were isolated from P. polyphylla var. pseudothibetica [41] and P. polyphylla var. chinensis [53], while two cholestane-type saponins, 90 and 91, were also found in P. polyphylla var. pseudothibetica [41] and P. polyphylla var. yunnanensis [48].

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The other saponins, with additional OH groups in positions 1, 5, 6, 21, 23, 24, and 25, i.e., 79 – 80, 84 – 89, and 92, were isolated from P. mairei [29], P. polyphylla var. yunnanensis [31] [52], P. delavayi [35], P. quadrifolia [39], and P. polyphylla var. chinensis [51]. Particularly, 1-dehydrotrillenogenin (92) with a C(15)¼O group was isolated from P. quadrifolia for the first time [39]. Later, Wu et al. obtained two further saponins with an oxo group, 93 and 94, from P. polyphylla var. yunnanensis [30]. The corresponding aglycone, which is rarely encountered in steroidal saponins, was identified in the Paris genus for the first time. 2.2. Flavonoids. Eighteen flavonoids, 95 – 112, have been reported, constituting the second most frequent secondary metabolites from different Paris species (Table) [13] [16] [19] [39] [40] [45]. These compounds occur mainly in two plants, P. axialis and P. polyphylla var. yunnanensis. Compounds 95 – 109 belong to the flavone type. Among them, 96 – 102, 104, 105, and 107, were isolated as flavonoid glycosides. Most of the glycosides had the sugar moiety at C(3), and some of the glucose moieties were linked to C(7) in 98, 99 and 107, or another sugar moiety in 96 – 99, 101, 102, and 105. Compound 110 is of chalcone type. Additionally, the dimers 111 and 112 feature the biflavone-type flavonoids. 2.3. Phytoecdysones. Five phytoecdysones, 113 – 117, were found in different Paris species [10] [16 – 17] [20] [24] [33] [37] [40] [54], with b-ecdysone (113) being the most common compound, while paristerone (116) was only isolated from P. polyphylla [54]. From P. verticillata, a-ecdysone (115) and ajugasterone (117) were obtained [40]. 2.4. Phytosterols. Four phytosterols, 118 – 121, were isolated from Paris species [16 – 18] [20] [24] [37] [40]. Compounds 118 and 119 belong to the ergostane type, and 120 and 121 are of stigmastane type. All of them were simultaneously isolated from P. polyphylla var. pseudothibetica by Zhao et al. [18]. 2.5. Phenylpropanoids. Two novel phenylpropanoid glycosides, 122 and 123, and a novel phenolic glycoside, 124, were reported from P. polyphylla var. yunnanensis [13] [14]. 2.6. Others. From the rhizomes of P. polyphylla var. yunnanensis, a sphingolipid, 125, and ethyl a-d-fructofuranoside (126) were obtained for the first time by Wang et al. [11] [12]. Two oligosaccharides, heptasaccharide (HS) and octasaccharide (OS), were isolated from the H2O extract of the rhizomes of P. polyphylla var. yunnanensis. These structures were identified as d-Glc-(1 ! 6)-b-d-Glc-(1 ! 6)-b-d-Glc-(1 ! 6)-b-d-Glc(1 ! 6)-b-d-Glc-(1 ! 6)-b-d-Glc-(1 ! 4)-a-d-Man and d-Glc-(1 ! 6)-b-d-Glc-(1 ! 6)b-d-Glc-(1 ! 6)-b-d-Glc-(1 ! 6)-b-d-Glc-(1 ! 6)-b-d-Glc-(1 ! 6)-b-d-Glc-(1 ! 4)-ad-Man, respectively [55]. Additionally, Zhang et al., and Wang and Lin provided a comprehensive survey of the concentrations of 14 trace elements, some of them being toxic (Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, V, and Zn) in samples of P. polyphylla var. yunnanensis and P. polyphylla from China [2] [56]. 3. Biological Activities. – 3.1. Antitumor Activity. In recent years, the EtOH, H2O, and MeOH extracts of P. polyphylla were shown to exhibit a marked growth-inhibitory effect on three tumor cell lines, including H22 , S180 , and S37 tumor cells, in a dosedependent manner [57] [58]. P. polyphylla also displayed a predominant inhibitory effect on six human digestive system tumor cell lines, i.e., human liver carcinoma

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(HepG-2 and SMMC-7721), human gastric cancer (BGC-823), human colon adenocarcinoma (LoVo and SW-116), and esophagus adenocarcinoma cell lines (CaEs-17), with IC50 values ranging from 10 to 30 mg/ml [59]. To detail the effective components in Rhizoma Paridis saponins (RPS) and to discuss the preliminary mechanism of antitumor effects in vivo and in vitro [60], Man et al. investigated a mixture isolated from RPS. The mixture of six paridis saponins showed powerful antiproliferation effects of LA795 cell migration by inducing apoptotic cell death and inhibiting the migration of the cancer cells [21]. It was also established that diosgenin and pennogenin saponins inhibit the metastasis of B16 melanoma cells, and the diosgenin saponins showed strong suppression of enzyme activity of MMP-2 and MMP9 [61].

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Recently, several main steroid saponins have been studied in several randomized controlled trials to evaluate their effects and mechanisms mainly on antitumor performance. The growth-inhibitory effect of dioscin (7) on human myeloblast leukemia HL-60 cells cancer cell lines was significantly strong with an IC50 value of 7.5 mm [62]. The studies on 7 have been conducted to better understand the underlying mechanism of the antitumor activity of Paris. It was reported that 7 induced differentiation and apoptosis in HL-60 and HeLa cells by activating caspase-9 and caspase-3, and down-regulating of anti-apoptotic Bcl-2 protein in a dose-dependent manner [62] [63]. Liu et al. found that dioscin (7) also induced apoptosis in human chronic myelogenous leukemia K562 cells by arresting the cell cycle in the G2/M phase and subsequently inducing apoptosis [64]. Trillin (2), one of the hydrolysates of 7, displayed similar cytotoxicities against K562 cells with an IC50 value of 7.5 mm [64]. Methyl protoneogracillin (58) was found to possess cytotoxic activities against leukemia and eight solid tumor cell lines with GI50 values < 100 mm, especially selectively against two leukemia lines (CCRF-CEM and RPMT-8226), one colon cancer line (KM12), two central nervous system (CNS) cancer lines (SF-539 and U251), one melanoma line (M14), and one breast cancer line (MDA-MB-435), with GI50 values  2.0 mm [65]. Recent research disclosed that polyphyllin D (8) is a potent apoptosis inducer through mitochondrial dysfunction in drug-resistant HepG2 cells [66], and has inhibitory effects on the growth of human breast cancer cells and in xenograft [67]. The proteomic and transcriptomic analyses revealed that 8 induced the cytotoxic effect through a mechanism initiated by ER stress, followed by mitochondrial apoptotic pathway [68]. Polyphyllin D (8), which implied a potential therapeutic development in cancer treatment, suppressed the growth of human microvascular endothelial cell line HMEC-1 at 0.1 – 0.4 mm concentration without toxic effects, and significantly inhibited endothelial cell migration and capillary tube formation at 0.3 and 0.4 mm [69] concentration, respectively. Gracillin (10) was cytotoxic against most cell lines with GI50 , TGI, and LC50 values at mm levels, but it had no activity against EKVX (non-small cell lung cancer), HT29 (colon cancer), OVCAR-5 (ovarian cancer), and SN12C (renal cancer) [65] cell lines. Formosanin C (14), which was isolated from Paris formosana Hayata, induced apoptosis of HT-29 cells characterized by exposure of phosphatidylserine, accumulation of cells at the sub-G1 phase, fragmentation of DNA, and change of nuclear morphology in a time- and dose-related manner [70]. In addition, it was found that 14 would retard the growth of subcutaneously transplanted MH134 mouse hepatoma at concentrations up to 2.5 mg/kg by activating caspase-2. Our preliminary research revealed that 14 suppressed enzyme activity of MMP-2 and MMP-9, and protein expression of MMP-1, -2, -3, -9 and -14 excreted from LA795 cells. Also, formosanin C (14) displayed much more effective inhibitions of tumor growth and pulmonary metastasis in T739 mice than cisplatin did [71]. Paris VI (22), paris H (25), and paris VII (32) as pennogenyl saponins also exhibited some cytotoxicity to mouse lung cancer LA795 cells and mouse B16 melanoma cells [11] [17] [19]. 3.2. Immunomodulating Effects. Formosanin C (14) was shown to significantly inhibit the specific lymphocytic response of lymph node and spleen cells to S-antigen at a dose of 1.5 mg/kg. The dosage of 14 obviously delayed the onset of S-antigen-induced experimental autoimmune uveitis in guinea pigs [72]. Formosanin C (14) also displayed significant enhancement of the blastogeninc response of human peripheral blood cells

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to phytohemagglutinin and increased the 3H-thymidine incorporation of ConAstimulated lymphocytes at concentrations of 0.1 and 0.01 mm. In addition, the intraperitoneal treatment with 14 potentially enhanced the activity of 5-fluorouracil (5-FU) against MH-134 mouse hepatoma [73]. b-Ecdysone (113) and the partially hydrolysis products of formosanin C (14), dioscin (7), also increased 3H-thymidine incorporation of ConA-stimulated lymphocytes maximally at 0.01 mg/ml [33]. In 2007, Zhang et al. reported that three diosgenyl saponins (paris V (3), polyphyllin D (8), and formosanin C (14)) enhanced phagocytic activity, and directly induced respiratory burst response in RAW 264.7 cells; however, diosgenin (1) had no PMA-triggered respiratory burst response [74]. 3.3. Hemostatic and Hemolytic Activities. It was reported that P. polyphylla var. chinensis, P. polyphylla var. yunnanensis, P. fargesii, and P. vietnamensis showed the haemostatic activities by reducing the values of bleeding time and clotting time. However, these species were not haemostatic at low concentration, and the main effective constituents were pennogenin saponins [75]. Paris H (25) was found to induce the aggregation of platelets in a dose-dependent manner, depending on the production of ADP and TXA2 after activation of platelets, and a high dose of this compound (30 mm) might induce a nonreversible aggregation [76]. On the contrary, RPS of P. polyphylla var. yunnanensis showed a hemolytic activity at concentrations > 0.01 mg/ ml, and the hemolysis intensity increased dose-dependently [77] [78]. 3.4. Antifungal, Antiviral, and Anthelmintic Activity. Compound 34 from P. polyphylla was evaluated for their antifungal activity against Cladosporium cladosporioides and Candida species, and showed activity comparable to those of some commercial products [6]. That the H2O and EtOH crude extracts of P. polyphylla showed significantly inhibiting effects on A-type and Asia A-type flu virus [5]. The 95% EtOH extract of P. polyphylla exhibited good anti-enterovirus 71 (EV71) and coxsackievirus B3 (CVB3) activities with IC50 values in the range of 78.46 – 125.00 and 126.39 – 197.15 mg/ml, respectively, and significantly increased IL-6 production in both EV71- and CVB3-infected cells. The results revealed a high correlation between the high amounts of IL-6 induction and the antiviral replication activity of the extract [79]. The anthelmintic activities of the crude extracts of P. polyphylla and pure compounds were evaluated by Wang et al., and the MeOH extract showed a promising anthelmintic activity against Dactylogyrus intermedius (EC50 value of 18.06 mg/l). Both dioscin (7) and polyphyllin D (8) were found to exhibit significant activities against D. intermedius with EC50 values of 0.44 and 0.70 mg/l, respectively, which were more effective than the positive control, mebendazole (EC50 1.25 mg/l) [80]. 3.5. Myometrial Contraction, Cardiovascular, and Gastrointestinal Effects. It was found that myometrial contraction stimulated by RPS of P. polyphylla var. yunnanensis was mediated by an increase in [Ca2 þ ]i via influx of extracellular calcium and release of intracellular calcium. Paris H (25) enhanced the contractile response of rat myometrium with advancing pregnancy, representing a new type of contractile agonist for the uterus [9]. The H2O extract of P. polyphylla var. yunnanensis was found to partly suppress the production of endothelin, and showed significant vascular-relaxing activities of rat aorta in vitro [5]. Compounds 7, 14, 25, and 32 were found to potently strongly inhibit gastric lesions induced by EtOH and indomethacin. Moreover, the protective effects of compounds 7 and 25 against EtOH-induced gastric lesions were

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attenuated by pretreatment with indomethacin and N-ethylmaleimide, and they weakly inhibited acid secretions in pylorus ligated rats [8]. 3.6. Analgesic and Sedative Effects. Six Paris species (P. polyphylla var. yunnanensis, P. polyphylla var. chinensis, P. fargesii, P. thibetica, P. vietnamensis, and P. stenophylla) exhibited effective analgesic and sedative activities. The analgesic effects of P. polyphylla var. yunnanensis and P. polyphylla var. chinensis were stronger than those of other species, while P. polyphylla var. chinensis, P. fargesii, and P. thibetica showed better sedative effect [81]. 3.7. Plant Growth Regulatory Activity. Two oligosaccharides, heptasaccharide (HS) and octasaccharide (OS), showed plant growth regulatory activities at low concentrations, and they can stimulate the shoot formation of P. polyphylla var. yunnanensis, root hair growth of Panax japonicus var. major, as well as both the growth and saponin accumulation of Panax ginseng hairy roots [55] [82]. Four oligosaccharides (penta-, hexa-, hepta-, and octasaccharide) derived from P. polyphylla var. yunnanensis were shown to possess growth-regulatory activities in the tobacco (Nicotiana tabacum L.), too [83]. 4. Concluding Remarks. – The genus Paris comprises 24 species, and many of them have been used as traditional herbal medicines. P. polyphylla var. yunnanensis and P. polyphylla var. chinensis were documented in the Chinese Pharmacopoeia [84] [85]. The extensive phytochemical investigations on several Paris species led to the isolation of 126 compounds, many of which exhibit strong bioactivities, whereas there are still several Paris species that have received little attention, and many constituents are still unknown. As a result, we consider it necessary to search for more potentially bioactive components from this genus, conducting further phytochemical and biological investigations. This project was financially supported by the National Natural Science Foundation of China (30873378), P. R. China.

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