an overview of paris polyphylla, a highly vulnerable medicinal...

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An Overview of Paris polyphylla, a Highly Vulnerable Medicinal Herb of Eastern Himalayan Region for Sustainable Exploitation

Arcadius Puwein1,* and Shiny C. Thomas2

1Department of Biotechnology, Assam Don Bosco University, Guwahati, India; 2Department of Biochemistry, Assam Don Bosco University, Guwahati, India

A R T I C L E H I S T O R Y

Received: February 15, 2018 Revised: May 07, 2018 Accepted: May 14, 2018 DOI: 10.2174/2210315508666180518081208

Abstract: Paris polyphylla is a member of the family of Melanthiaceae (earlier Trilliaceae or Lili-aceae). It is known as “Love Apple” in English. This erect and herbaceous plant is found mostly in South East Asia and was documented for the first time in 1985 in the Chinese pharmacopeia. It is a traditional medicinal herb known to have many medicinal properties like anticancer, antimicrobial, anti-tumor, cytotoxicity etc. The objective of this paper is to highlight the major research works on this miraculous herb and include updated information on its developments that have been rapidly taking place in recent years. There have been new approaches in an effort to classify the plant using high-throughput RNA-Seq technologies, mass propagation and conservation through tissue culture, understanding the mechanism of the action of steroidal saponins as a major anticancer activity, and new bioactive compounds have been added in phytochemistry. The current article attempts to enu-merate an extensive overview of P. polyphylla on classification, morphological characteristics, habi-tat, reproductive phenology, traditional uses, distribution and availability, propagation, phytochemis-try, biological activities, molecular analyses, and conservation.

Keywords: Paris polyphylla, herb, steroidal saponins, rhizomes, bioactive compounds, biological activities.

1. INTRODUCTION

The pursuit of plant-based medicines is growing rapidly worldwide. In recent decades, the natural products have gained importance in the field of pharmaceuticals [1]. Paris polyphylla Sm. is one of the medicinal plants which is part of this momentum of growth and recognition in the biological activities. It is one of the many medicinal herbs of Asia. It is an erect and herbaceous plant. The herb has a spider-like flower that throws out long, thread-like, yellowish green petals throughout most of the warm summer months and into the autumn. The genus name is derived from ‘pars’ referring to the symmetry of the plant. The species polyphylla means many leaves; ‘poly’ meaning many and ‘phyla’ meaning leaves [2]. P. polyphylla which is known in English as “love apple” belongs to the family of Melanthiaceae (earlier Trilli-aceae or Liliaceae) [3]. The herb is mostly found in India, China, Bhutan, Laos, Myanmar, Nepal, Thailand, and Viet-nam [4]. It was documented in the “Chinese pharmacopeia” in 1985 for the first time. It was first recorded in “Shennong Herb” named as Zaoxiu. It appeared with the same name in Li Shizhen’s “Compendium of Materia” [5].

Being known as a wonder herb, a number of works have been carried out in the last few years. The three reviews pub-lished recently are worth mentioning - Medicinal properties *Address correspondence to this author at the Department of Biotechnology, Assam Don Bosco University, Guwahati, India; Tel: +91857586804; Fax: +917005139926; E-mail: [email protected]

of Paris polyphylla published in 2012, chemical constituents of plants from the Genus Paris published in 2014, and distri-bution and phytomedicinal aspects of Paris polyphylla from the Eastern Himalayan Region published in 2015. All the three reviews accentuated on a particular topic only (on me-dicinal properties, chemical constituents, distribution and phytomedicinal). Moreover, within two or three years, there has been lots of development in research on this herb. This paper compiles almost all the major works on this plant such as classification, morphological characteristics, habitat, re-productive phenology, traditional uses, distribution and availability, propagation, phytochemistry, biological activi-ties, molecular analyses, and conservation. New biotechno-logical approaches have been introduced and updated in the utilization of this plant. Therefore, this paper enumerates research reported in index journals, updates the new ap-proaches and investigates the future possibilities of the plant [2].

2. CLASSIFICATION

P. polyphylla is extremely polymorphic. This implies that its classification is very complicated. Its classification is therefore simplified using Table 1. The classification of Paris has long been in dispute and still unresolved. Many authors classified the genus Paris into sub-genus and sec-tions (Table 1). Based on floral and leaf merosity, Hara (1969), Li (1984, 1998) and Mitchell (1987, 1988) recog-nized Paris as a single genus [6]. Hara further divided the 14

2 The Natural Products Journal, 2019, Vol. 9, No. 1 Puwein and Thomas

Table 1. The Classification of Paris polyphylla according to Ji Y.H et al.

Genus Parameters Sub-Genus Sections Author (s)

Paris Floral and leaf merosity Single genus - Hara, Li H and Mitchell

Paris Fruit and seed Single genus (14 species) Paris

Kinugasa Euthyra

Hara

Paris Type of fruit, the shape of an ovary, seed morphology, and shape of rhizome

Paris Kinugasa Daiswa

- Takhtajan

Paris (11 species) Kinugasa (1 species)

Paris (5 species) Axiparis (5 species)

Paris Comprehensive taxonomy

Daiswa (13 species)

Dunnianae (1 species) Marmoratae (2 species)

Euthyra (8 species ) Farge sianae (1 species) Thibeticae ( 1species)

Ji H Y.H et al.

Paris DNA sequence Paris

Kinugasa Daiswa

- Ji Y.H et al.

known species at the time into three sections: Paris, Kinu-gasa, and Euthyra, based on fruit and seed characters [7]. In 1983, Takhtajan divided Paris into three major genera: Paris, Kinugasa, and Daiswa.

But in the most recent comprehensive classification, Ji Y.H et al., recognized subgenus Paris consists of 11 species and subgenus Daiswa consists of 13 species. Subgenus Paris was divided into sections Kinugasa (one species), Paris (five species) and Axiparis (five species), whereas subgenus Daiswa was divided into sections Dunnianae (one species), Euthyra (eight species), Marmoratae (two species), Farge sianae (one species) and Thibeticae (one species) [5]. How-ever, from recent phylogenetic studies based on DNA se-quence, data support the classification of Paris into three genera as shown and simplified in Table 1 (Daiswa, Kinu-gasa, and Paris). P. polyphylla belongs to the sub-genus Daiswa and section Euthyra. P.polyphylla is furthered di-vided into 11 different varieties -1) Paris polyphylla Smith 2) Paris polyphylla var. polyphylla 3) Paris polyphylla var. yunnanensis 4) Paris polyphylla var. chinensis 5) Paris polyphylla var. nana 6) Paris polyphylla var. alba 7) Paris polyphylla var. stenophylla 8) Paris polyphylla var. minor 9) Paris polyphylla var. latifolia 10) Paris polyphylla var. pseudothibetica 11) Paris polyphylla var. kwangtunesis. Among these 11 varieties, the ones found in Uttarakhand and Northeastern Himalayas of India along with other neighbor-ing countries are Paris polyphylla Smith, Paris polyphylla var. polyphylla, Paris polyphylla var. yunnanensis and Paris polyphylla var. stenophylla. The most common variety col-lected and identified from Northeast India is Paris poly-phylla Smith [6].

3. MORPHOLOGICAL CHARACTERISTICS

P. polyphylla is a perennial, rhizomatous, herbaceous plant with green and unbranched aerial part. The aerial part

contains the single stem-like structure and the 2-3 whorls of leaves are present on the nodes. The flowering period may last up to three months. It has odd flowers with long yellow radiating anthers [2]. The morphological characteristics of the herb are given below:

Habit: aerial, herbaceous, rhizomatous, erect plant. Stem: unbranched, smooth, 50-100 cm tall, 1-2.5 cm

thick. Leaf: Simple, arranged in whorls, petiolate, lanceolate,

reticulate with three primary veins, smooth margin, above the green leaves are yellow-green spider-like flowers.

Inflorescence: It forms a closed whorl at the initial growth, covered by the sepals enclosing the tepals, the an-thers and the stigma.

Flower: The flowers bloom at the terminal and they are solitary, yellowish green, contain both male and female gametes within the same flower (monoecious), sepaloid outer is larger and inner is smaller, tepal 3-5.

Androecium: stamens 6-11 and are free. Gynoecium: 1 pistil, 3-5 carpels, syncarpous (carpels

fused), ovary superior. Seed: Reddish orange, a mature fruit contains 50-60

seeds [8].

4. HABITAT

P. polyphylla is a shade loving plant and grows under the canopy closure of more than 80%, at an altitude of 1300 - 2500 m above sea level. It grows mainly in a forest with bamboo groves, grassy or rocky slopes, stream-sides, mixed conifer forests and scrub thickets [4]. It is a slow germinating herb which takes about seven months to sprout from the

An Overview of Paris polyphylla, a Highly Vulnerable Medicinal Herb The Natural Products Journal, 2019, Vol. 9, No. 1 3

Table 2. Traditional Uses of P. polyphylla.

Country Plant Parts Ailments References

Rhizomes Vermifuge, anti-helminthic [11]

Juice of rhizomes Gastric, menstruation pain [12] Nepal

Paste of rhizomes Cuts, wounds and to remove worms [12]

The powdered roots Diarrhoea [13] India

Rhizomes Antidote for snake & insect poison [14]

Rhizomes Haemostatic, anti-inflammatory agent, traumatic injuries, snake bites,

abscess, parotitis, mastitis, bone fractures and anti-tumor [15]

Rhizomes Detumescent, demulcent, anti-febrile, alexipharmic [16]

Rhizomes Reducing swelling, relieving pain, sore throat, snake bites and bruises [17]

Rhizomes Tumor, hemostasis and inflammation counteraction [18]

China

Rhizomes Immunity adjustment, analgesia, and anti-inflammation [19]

seed. P. polyphylla thrives well inside the deep forest where human interference is minimal. It grows in humus-rich and well-drained soil. Waterlogging is found to be lethal for this herb. The plant is able to rehabilitate in artificial habitats while maintaining similar temperatures and at similar alti-tudes. Plants that lack inflorescence are usually shorter in height. The research on its adaptability has displayed that when the whole plant was taken outside its natural habitat, it showed sign of growth at the initial year but failed to flower in an artificial habitat. If the plant flowered, it failed to set fruit and seed. It was also observed that this species thrives well in the presence of some common associated species within 5m perimeter. These common associated species in-clude trees, herbs, and climbers. Further research is required to understand their mode of interaction with other species, those that boost its growth [9].

5. REPRODUCTIVE PHENOLOGY

Knowing the pattern and process of the reproduction in plants is one of the important steps for effective conserva-tion. Mass multiplication, either vegetative or in vitro repro-duction, depends on the basic knowledge of reproductive phenology. The rhizome of P. polyphylla remains in dor-mancy for almost 4-5 months. The rhizome sprouts in the months of February-March. It flowers in the month of March-April and sheds leaves in October-November. Al-though reproductive phenology has been studied and re-ported, the herb does not have an exact uniform pattern of time for flowering, sprouting, and senescence. It was ob-served that when the herb is taken out of the natural habitats and artificially grown in pots, a slight variation is noticed in sprouting, flowering, and senescence [9]. This might be due to many external and internal factors (environment, soil nu-trients, habitat, sunlight, human interference, etc).

6. TRADITIONAL USES

China, India, Nepal, and the whole region of Indo-Burma are endemic to many medicinal plants. These countries have

traditionally used P. polyphylla to relieve various ailments. The herb is a well-known Traditional Chinese Medicine (TCM). The Indian tribes of Arunachal Pradesh, Nagaland, Manipur, Meghalaya, Uttarakhand, and Sikkim have been using it as folk medicines, albeit some ethnic communities are not very conscious about its remarkable medicinal poten-tial [10]. The various uses of the plant are indicated in Table 2.

7. GEOGRAPHICAL DISTRIBUTION AND AVAIL-ABILITY

Internationally P. polyphylla is found mostly in East Asia, Himalayan regions and in Europe. It is an extensively growing species in China with the Yunnan-Guizhou Plateau as the center of diversity and thrives well also in Bhutan, Laos, Myanmar, Nepal, Thailand, and Vietnam [4].

In India, the presence of P. polyphylla is reported in many temperate climatic regions, mainly in the Eastern Hi-malayan regions. Each ethnic group has its own local name for the plant as shown in Table 3. But some of the local names have not been reported yet.

8. PROPAGATION

P. polyphylla grows well in moist, humus-rich soil, and in full or partial shade. However, its regeneration through seed is a real challenge due to the prolonged seed dormancy and slow germination. It is propagated by portions of rhi-zomes, and so can be called as ‘seed rhizomes.’ Hence rhi-zomes from the wild are the only source for propagation as well as for medicinal purposes. This leads to a great decline of the herb. It is on the edge of extinction due to excessive illegal collection for many years [28]. Moreover, this peren-nial plant can only be harvested after growing for 5–7 years, which aggravates the shortage of its resource [29]. To pre-serve this natural resource and ensure a stable and renewable source of P. polyphylla for medicinal purposes, successful propagation is imperative [30]. This calls for an urgent need


Table 3. Geographical Distribution and Availability of P. polyphylla in India.

State District Village/Region Local Name References

Arunachal Pradesh Kameng, Subansiri, Kurung Kume, Siang,

Lohit, Tirap and Changlang - Do-Tala [20]

Senapati Hengbung, Maram, Purul and Ma-

kui regions Manipur

Tamenglong Puilong Village

Singpan [13, 21, 7]

Uttarakhand - - Satwa [13]

Himachal Pradesh - - - [22, 23]

Jammu & Kashmir - - - [23]

Mizoram - - - [7, 24]

Sikkim - - - [25]

Tuensang Pangsha village

Phek Chida region

Kohima Arudara region Nagaland

Mokokchung Longkum village

- [9, 26]

Meghalaya West Khasi Hill Nongstoin region Sohbsein [27]

(-) not reported to discover alternate resources from which the continuous supply can be obtained.

8.1 Planting Material

The vegetative propagation of the plant has been achieved through rhizomes and it occurs in masses due to aggregation of large clumps. The older plant has massive rhizomes with multiple buds. It grows intertwined and en-tangle each other and has a wavy nature in appearance. Therefore, the seed rhizomes are used in different ways in cultivation practices that are given below.

8.1.1. Rhizome Cuttings

The older rhizomes are split into pieces so that each rhi-zome gives rise to shoot buds and later converted into plants in the raised soil bed within 4-5 months. The percentage of viable regenerated plantlets from rhizome cuttings were found ~49%, and only 7% of the regenerated plantlets showed fertile nature that bears the inflorescence [31]. The percentage of the regeneration is found considerably low which is one of the main drawbacks found in the cultivation and propagation of this plant from rhizome cuttings. The effect of plant growth regulators (PGRs) in sprouting and rooting have also been studied and the results show that in-dole-3-butyric acid (IBA) and gibberellic acid (GA3) at dif-ferent concentrations (0, 50, 100 mg/l) were highly effective (83.33% and 73.33 %) as compared to control (46.66 % and 36.66 %). The combination of IBA (100 mg/l) and GA3 (100 mg/l) presented the best result in sprouting and rooting of the rhizomes. The soil combinations (soil:loam:sand) in the ratio 3:2:1were also significant for proper sprouting and rooting [32].

8.1.2. Rhizome Fragmentations

This technique involves the breaking of the masses of rhizomes into each individual rhizome with many buds and sowing in the prepared bed in the polyhouse. Of the total separated rhizomes planted, ~75% rhizomes could sprout successfully and grow into a plant. Though the rhizomes fragment showed a better result than rhizomes cutting in cultivation, the availability of sufficient material (rhizome fragments) is one of the major challenges in the massive cul-tivation of this plant at the moment [32]. Therefore, mass production of this herb is a prerequisite for sustainable utili-zation. Hence, the in vitro propagation has immense impor-tance in the multiplication of P. polyphylla since very scanty research have been conducted so far.

8.1.3. Micropropagation

Raomai Shiveirou et al. (2014) have reported direct so-matic embryogenesis and subsequent plant regeneration of P. polyphylla. Their study shows that the highest frequency of somatic embryogenesis, and mean number of somatic em-bryos (SEs) were obtained on ½ MS medium directly with-out an intermediate callus phase. The highest frequency of SE germination and seedling to plantlet conversion occurred on ½ MS medium by adding 0.5 mg/l gibberellic acid, 0.05 mg/l 6-benzylaminopurine, and 0.1 mg/l α-naphthalene ace-tic acid [33].

This result is followed by another investigation by Raomai Shiveirou et al. in 2015. They developed an efficient regeneration protocol for P. polyphylla. through the forma-tion of mini-rhizomes (MRs) using transverse thin cell layer (tTCL) culture technique. Elicitation of MRs liquid culture


with chitosan, salicylic acid (SA) and yeast extract enhanced the production of steroidal saponins but resulted in reduced growth rate. Highest total steroidal saponins content (87.66 ± 1.66 mg/g DW) was achieved in cultures treated with SA at 50 mg/l after 30 days of elicitation which is 3.6 times higher than the in vivo rhizome [34].

9. PHYTOCHEMISTRY

P. polyphylla produced many bioactive compounds which are vital for various treatments. The most important compounds are alkaloids, flavonoids, saponins, carbohy-drates, cardiac glycosides, terpenoids, sterols, quinones, phe-nols, and tannins. Nearly 98 compounds were identified from the rhizome, which includes more than 30 steroidal saponins [35]. Most bioactive compounds were isolated from the rhi-zomes, but recently many chemical constituents were also extracted from the stems and leaves.

9.1. Chemical Compounds Isolated from Rhizomes

The active components present in P. polyphylla are the steroidal saponins, dioscin, polyphyllin D, and balanitin 7 [36]. The Paris saponins account more than 80% of the total compounds of P. polyphylla. Other important compounds isolated from this plant are Paris saponin I (diosgenin3-O-α-L-rha-(1-2)-[α-L-arab-(1-4)]-β-D-glu), Paris saponin II (diosgenin3-O-α-rha-(1-4)-α-L-rha-(1-4)-[α-L-rha-(1-2)]-β-D-glu), Paris saponin III, polyphyllin VI and polyphyllin VII [18]. Steroid saponins from P. polyphylla are classified into two main groups: diosgenin (Dio) glycosides and penno-genin glycosides. Furthermore, D-glycopyranoside, L-rhamnopyranoside, and L-arabinofuranoside are the main glycosides linked in the structure of steroid saponins [37].

In 2005, Devkota isolated six compounds from P. poly-phylla which he collected from Parbat district, Nepal [38, 39]. These compounds are: i) Saponin-1 ii) Polyphyllin C iii) Poly-phyllin D iv) Przewalskinone B v) Stigmasterol vi) Stigmas-terol-3-O- β -D-glucoside [39]. Huang Yun et al. in 2007 ex-tracted a novel steroidal saponin together with the 12 known compounds from P. polyphylla var. chinensis. The novel com-pound was attained as an amorphous solid. The 12 known compounds were identified as steroids and their structures (Table 4) were recognized by 13C NMR spectrum (in pyri-dine-d5) [14, 15]. Again in 2007 three new steroidal saponins were isolated from the rhizome of P. pollyphylla var. yun-nanensis. Two compounds were a mixture of a pair of stereoi-someric new spirostanol saponins and a new cholestane saponin [40]. Along with 18 known steroidal saponins, two new furostanol saponins (designated as parisyunnanoside A and parisyunnanoside B) and one new spirostanol saponin (designated as parisyunnanoside A) were isolated from the rhizome of P. polyphylla var. yunnanensis by Yu Zhao et al. in 2009 [41]. Jin-Chao Wei et al. in 2014 identified various compounds, such as steroid saponins, phytoecdysones, phytos-terols, phenylpropanoids, and flavonoids, from six Paris spe-cies (P. polyphylla var. yunnanensis, P. verticillata, P. pubes-cends, P. axialis, P. polyphylla var. pseudothibetica, and P. fargesii). They found that steroid saponins are the main con-stituents of the six species, along with many other constitu-ents, including flavonoids, phenylpropanoids, ecdysteroids, and phenolic glycosides. They conducted extensive phyto-

chemical investigations on several Paris species which led to the isolation of 126 compounds (not shown in Table 4). In 2016, Ling-Yu Jin et al. isolated two new highly oxygenated spirostanol saponins named as paristenosides A and B from the rhizomes of P. polyphylla var. stenophylla [42]. Some of the phytoconstituents isolated and identified from Paris poly-phylla is summarized in Table 4. Many of these compounds exhibit strong bioactivities but there are still several species that have received little attention, and many constituents are still unknown [43]. Some of the important structure of isolated compounds from this herb is given in Fig. (1).

9.2. Compounds Isolated from the Stems and Leaves

Isolation of compounds from the stems and leaves are significant as they can regenerate every year. Phytochemical analysis of the ethanol extracts of stems and leaves of P. polyphylla var. yunnanensis has yielded six new spirostanol saponins, named as chonglouosides SL-1-SL-6 (1-6), along with one known sapogenin and 18 known steroidal saponins [49]. When the stems and leaves of the same species were further investigated using water, 80% ethanol and 95% etha-nol as solvents, three C22-steroidal lactone glycosides were isolated. Two of these are new compounds, designated as chonglouoside SL-7 and chonglouoside SL-8 [50]. The des-ignated name and molecular formula of the newly isolated compounds are given in Table 5.

10. BIOLOGICAL ACTIVITIES

P. polyphylla is reported to exhibit potential biological activities which are substantiated by several studies. Studies have been done in China on the pharmacology of the herb focusing on anticancer and antimicrobial activities. The rhi-zome of P. polyphylla is used to clear heat, remove toxicity, cool the liver, relieve swelling and pain, and arrest convul-sion. The rhizomes of P. polyphylla var.yunannensis and P. polyphylla var. chinensis are used for haemostatic activity [51], anti-fertility, spermicidal enhancement and sedative [38], anti-tumor, anti-inflammatory, antibacterial, brain and kidney protection, uterine contraction, antioxidant, menor-rhagia, metrorrhagia, metrostaxis [52], showed anticancer activity on several cell lines [53], and antifungal activities [14,49]. The plant extracts of P. polyphylla showed effective spermicidal activity against human and rat sperms. It pre-vents pregnancy up to 60% when tested in the rabbits [38]. Some compounds of the herb exhibit tyrosinase inhibitory activity and anti-leishmanial activity [39]. Recently, many studies of the herb accentuate in its anticancer activities.

10.1. Anticancer Activity

The P. polyphylla var. yunnanensis has been extensively investigated in China. Phytochemical and pharmacological studies identified steroid saponins as the main antitumor ac-tive components [54, 55, 56]. Paris saponins are a group of plant glycosides consisting of a steroid aglycone, to which one or more sugar chains are attached [57]. The aqueous, ethanolic and methanolic extracts of P. polyphylla showed their anticancer activity on several types of cancer cell lines. The biological activities of different steroid saponins are quite different from each other in exhibiting inhibition in many cancer cell lines as shown in Table 6.


Table 4. Some Chemical Constituents Isolated from the Rhizomes of P. polyphylla.

Plant Species Isolated Compounds References

Paris saponin I (diosgenin3-O-α-L-rha-(1→2)-[α-L-arab-(1→4)]-β-D-glu)

Paris saponin I (diosgenin3-O-α-rha-(1→4)-α-L-rha-(1→4)-[α-L-rha-(1→2)]-β-D-glu)

Paris saponin III (diosgenin 3-O-α-L-rhamnopyranosyl-(1→2)-[ α -L-rhamnopyranosyl-(1→4)]- β-D -glucopyranoside)

Polyphyllin VI (pennogenin-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside)

P. polyphylla

Polyphyllin VII (pennogenin-3-O-α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)[O-β-D-glucopyranosyl-(1→2)]-β-D-glucopyranoside)

[18]

Saponin-1 (diosgenin-3-O [α-L-rhamnopyanosyl (1Rha-2Glu)-α-L-rhamnopyranosyl (1Ara-4Glu)]-β-glucopyranoside)

Polyphyllin C (diosgenin-3-O [α-L-rhamnopyanosyl(1→3)-α-D-glucopyranoside)

Polyphyllin D (diosgenin-3-O[α-L-rhamnopyanosyl (1Rha-2Glu)-α-L-arabinofuranosyl (1Ara-4Glu)]-β-D glu-copyranoside)

Przewalskinone B (1,5-Dihydroxy-7-methoxy-3-methylanthraquinone)

Stigmasterol

P. polyphylla

Stigmasterol-3-O-β-D-glucoside.

[39]

Diosgenin

Pennogenin

Diosgenin-3-O-α-L-rhamnopyranosyl (1→2)-β-D-glucopyranoside

Pennogenin-3-O-α-L-rhamnopyranosyl(1→2)-β-D-glucopyranoside

Diosgenin-3-O-α-L-rhamnopyranosyl(1→2)[-α-L arabinofuranosyl(1→4)] -β-D-glucopyranoside

Pennogenin-3-O-α-L-rhamnopyranosyl(1→2)[-α-L arabinofuranosyl (1→4)]-β-D-glucopyranoside

Diosgenin-3-O-α-L-rhamnopyranosyl(1→2)-[β-D-glucopyranoside(1→3)]-β-D-glucopyranoside

Diosgenin-3-O-α-L-rhamnopyranosyl (1→4) -α-L rhamnopyranosyl (1→4)[α-L-rhamnopyranosyl (1→2)]-β-D-glucopyranoside

Pennogenin-3-O-α-L-rhamnopyranosyl(1→4) -α-L-rhamnopyranosyl (1→4)[α-L-rhamnopyranosyl (1→2)]- β-D-glucopyranoside

3-O-α-L-arabinofuranosyl(1→4)[ α-L-rhamnopyranosyl(1→2)] -β-D-glucopyranoside-β-D-chacotriosyl-26-O-β-D-glucopyranoside

2β, 3β, 14α, 20β, 22α, 25β hexahydroxycholest-7-en-6-one

P. polyphylla var. chinensis

2β,3β,14α, 20β,24β,25β hexahydroxycholest- 7-en-6-one

[14,15]

P. polyphylla var. chinensis

3b, 21-dihydroxy pregnane-5-en-20S-(22,16)-lactone-1-O-α-L-rhamnopyranosyl (1→2) -[β-D-xylopyranosyl (1→3)] -β-D-glucopyranoside.

[14]

(25R)-spirost-5-en-3b,7b-diol-3-O-α-L-arabinofuranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside

(25R)-spirost-5-en-3b,7a-diol-3-O-α-L-arabinofuranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside P.pollyphylla Smith var. yunnanensis 26-O-β-D-glucopyranosyl-(25R)- ∆ 5(6) 17 (20)-dien-16,22-dione-cholestan-3b,26-diol-3-O-α-L-arabinofuranosyl-(1→4)-

[α-L-rhamnopyranosyl-(1→2)] -β-D-glucopyranoside

[40]

26-O-β-D-glucopyranosyl-(25R)-5-ene-furost-3β,17α, 22α, 26-tetrol-3-O-α-L-arabinofuranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside

26-O-β-Dglucopyranosyl-(25R)-5, 20 (22)-diene-furost-3β, 26-diol-3-O-α-L-arabinofuranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside

P.pollyphylla Smith var.

yunnanensis (25R)-spirost-5-ene-3β, 12α-diol-3-O-α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)-[α-L-

rhamnopyranosyl-(1→2)]-β-D-glucopyranoside

[41]

24-O-β-D-galactopyranosyl-(23S,24S,25S)-spirost-5-ene-1b,3b,21,23,24-pentol-1-O-α-L-rhamnopyranosyl-(1→ 2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranoside P. polyphylla

var. steno-phylla. 21-O-β-D-galactopyranosyl-24-O-β-D-galactopyranosyl-(23S,24S)-spirost-5,25(27)-diene-1b,3b,21,23,24-pentol-1-O-

α-L-rhamnopyranosyl-(1→ 2)-[β-D-xylopyranosyl-(1→ 3)] -β-D-glucopyranoside

[42]


OHOHO

OH

OO

HOHO

OO

HO

HO

OO

HOHO OH

O

OHO

O

0HOHO

O

HO

O

O

O

OHO

HOHO

OH

Polyphyllin VI Polyphyllin VII

OHO

HOOH

O

O

O

OH

O

OHO

HOOH

O

H

H

H

OOH

H

O

OHO

HO CH3OH

O

O

OH

OH

O

OHO

HOOH

O

CH3

H

H

H

OOH

H

H3CCH3

OCH3

Polyphyllin D Polyphyllin I

OHO

HO

OHH

OO

HO

OH

O

HO

O

HO

O

OHO

HOHO

H

O

H

H OH

H

O

O

HOHO

OH

O

O

HOHO

O

HOO

OHO

HOOH

O

OHO

O

O

OH

Paris saponin II Paris Saponin VII

O

OR

O

O

OR

O

OH

Diosgenin Pennogenin

Fig. (1). Some important structure of compounds isolated from P.polyphylla. Polyphyllin VI [44], Polyphyllin VII. 10.2. Antimicrobial Activity

This magical herb has been reported to have antibacterial, antifungal and antiviral activities. Few of the compounds isolated from the stems and leaves of P. polyphylla var. yun-nanensis were found to be active against Propionibacterium acnes [51]. The roots of P. polyphylla have shown antibacte-rial action against Bacillus dysentery, B. paratyphi, B. typhi, Staphylacoccus aureas, Escherichia coli, Haemolytic strep-tococci, Meningococci. Certain compounds isolated from P. polyphylla var. yunnanensis showed significant antifungal activities against Saccharomyces cerevisiae hansen, Cla-dosporium cladosporioides and Candida albicans [14]. The endophytic fungus Pichia guilliermondii Ppf9 which was derived from P. pylyphylla var. yunnanensis also demon-strates strong antimicrobial activity against Agrobacterium

tumefaciens, E. coli, Pseudomonas lachrymans, Ralstonia solanacearum, Xanthomonas vesicatoria, B. subtilis, Staphy-lococcus aureus and S.haemolyticus [73]. When Enterovirus 71 (EV71), coxsackievirus B3 (CVB3) and control (ri-bavirin) were inoculated in the medium containing P. polyphylla Smith and incubated at 37ºC for 72h, anti-EV71 and CVB3 activities were observed. The anti-EV71 activity was reported to be stronger than that against CVB3. Moreover, it was observed that the compound extracts of the herb penetrated the viral capsid and degraded the viral RNA [44], Polyphyllin D [45], Polyphyllin I [46], Paris saponin II [47], Paris saponin VII [48], Diosgenin [29], Pennogenin [29]. and so inhibited the viral replication. The bioactive compounds of P. polyphylla also increased the production of IL-6 cytokine which further augments the antiviral activities [74].


Table 5. The New Compounds Isolated from the Stems and Leaves of P. polyphylla var. yunnanensis.

Designated Name

Molecular Formula

Isolated Compounds References

Chonglouoside SL-1.

C33H52O9 (25R)-spirost-5-en-3β,7α-diol-3-O-β-D-glucopyranoside

[49]

Chonglouoside SL2

C39H62O14 (23S,25R)-spirost-5-en-3β,23

α,27-triol-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside [49]

Chonglouoside SL3

C51H82O23 23-O-β-D-glucopyranosyl-(23S,25R)-spirost-5-en-3β,23α,27-triol-3-O-α-L-rhamnopyranosyl-

(1→2)-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranoside [49]

Chonglouoside SL4

C51H82O23 27-O-β-D-glucopyranosyl-(23S,25R)-spirost-5-en-3β,23

α,27-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucoyranoside

[49]

Chonglouoside SL5

C51H80O21 (25R)-7-oxospirost-5-en-3β-ol-3-O-α-L-rhamnopyranosyl-

(1→4)-α-L-rhamnopyranosyl-(1→4) [α-L-rhamnopyranosyl- (1→2)]-β-D-glucopyranoside

[49]

Chonglouoside SL6

C50H80O23 27-O-β-D-glucopyranosyl-(25R)-spirost-5-en-1β,3β,27-triol-1-O-α-L-rhamnopyranosyl-

(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranoside [49]

chonglouoside SL-7

C40H62O17 (20S)-3β, 16β, 20-trihydroxy-pregn-5-en-20-carboxylic acid (22, 16)-lactone-3-O-α-L-

rhamnopyranosyl-(1→4)-O-[α-L rhamnopyranosyl-(1→2)]-β-D-glucopyranoside [50]

Chonglouoside SL8

C40H60O16 3β, 16β-dihydroxypregn-5, 20-dien-carboxylic acid (22, 16)-lactone-3-O-α-L rhamnopyrano-

syl-(1→4)-O-[α-L-rhamnopyranosyl -(1→ 2)]-β-D-glucopyranoside [50]

10.3. Anti-Abnormal Uterine Bleeding

Abnormal Uterine Bleeding includes both dysfunctional uterine bleeding and bleeding due to structural causes, in-cluding fibroids, polyps, endometrial carcinoma and preg-nancy complications. It can also result from contraception [75]. Drugs such as progestins prostaglandin or a combina-tion of estrogen and progestins greatly decreased menstrual bleeding in patients with abnormal uterine bleeding. How-ever, most women are unwilling to opt for drugs because of side effects that often make them unsuitable for long-term use. Steroidal saponins extracted from the rhizome of P. polyphylla var.yunnanesis have been used in China as an alternative treatment of abnormal uterine bleeding which is comparatively less toxic. The study reported that the steroi-dal saponins extract reduced hemorrhage by approximately 95%. This includes the treatment of 300 cases of abnormal uterine bleeding, 122 cases of dysfunctional uterine bleeding, 103 cases of menorrhagia and 75 cases of other causes [76].

11. MOLECULAR ANALYSIS

P. polyphylla was subjected to molecular analysis with a view to solving problems related to its sustainable conserva-tion or classification. One of the major problems is that seeds of P. polyphylla var.yunnanesis germinate only 40% after 18 months or even two years of being in a state of dormancy in the natural environment [77]. This long dormancy may be due to the seed coat or the seed itself. Thus the transcriptome data of dormant seeds and their seed coats were sequenced and assembled using high-throughput RNA-Seq technolo-gies. A total of 146,671 unigenes with an average length of 923 bp (base pair) were identified. These genes showed

functional diversity based on different annotation methods. Then two small RNA libraries from seeds and seed coats respectively were sequenced. Their combining data showed that 263 conserved miRNAs belonging to at least 83 families and 768 novel miRNAs in 1174 transcripts were found [78]. The miRNAs were chosen as candidates for sequencing be-cause they play an important role in gene regulation in the development of many plant tissues and organs [79, 80]. Many transcription factors such as myeloblastosis-related proteins (MYB), growth-regulating factor (GRF), squamosa promoter binding protein-box (SBP- box), Apetala2 (AP2), and MADS-box gene families, have been shown to be regu-lated by miRNAs in plants [81]. This molecular analysis helps the researchers to predict that miRNAs were involved in the cell, metabolism and genetic information processing by direct and indirect regulation patterns in dormant seeds of P. polyphylla var. yunnanensis [78].

The sequencing of the complete chloroplast (cp) genome was driven by the problem of an unresolved fact of classifi-cation of Paris. The complete cp genome was chosen as the candidate for sequencing because it offered valuable infor-mation for plant phylogenetic analyses and species identifi-cation and in the reconstruction of complex evolutionary relationships in plants [82, 83]. Albeit, the previous mor-phology-based classification and molecular phylogeny have been subjected to numerous critical revisions but not without controversial issue. So, to enhance the understanding of the classification of this genus, the complete cp genomes of 11 Paris taxa were sequenced [84]. The complete cp genomes of the 11 Paris taxa were compared with the previously re-ported cp genome of P. verticillata [85] which ranged from 157,379 to 158,451bp. The cp genomes consist of a pair of


Table 6. Anticancer Activities of P. polyphylla.

Cancer Types Bioactive Compounds Mechanism of Action References

Polyphyllin VII Induces apoptosis via intrinsic and extrinsic pathway [58, 59] Liver Cancer

Rhizoma paridis saponins (RPS) Induces reactive oxygen species (ROS) and oxidative

damage of DNA [60, 61, 62]

Polyphyllin VI Polyphyllin VII

Induces G2/M cell cycle arrest and triggers apoptosis. [44] Lung Cancer

Rhizoma paridis saponins (RPS) Inhibits the migration of the tumor cells [44,63]

Human Chondrosarcoma

Crude extract Cytotoxicity and apoptosis [64]

Ovarian Cancer Aqueous extract of P. polyphylla

Apoptosis via suppression of peroxisome PGC – 1alpha [65]

Cervical Cancer Paris saponin VII Apoptosis through intrinsic apoptotic pathway [48]

Human Chronic Myelogenous Leukemia

Polyphyllin D Induces apoptosis via mitochondrial apoptotic pathway [66]

Human Glioma Polyphyllin D Apoptosis via JNK pathway [45]

Esophageal Cancer P.polyphylla Smith extract (PPSE) Apoptosis and increased expression of Connexin26 and

formation of gap junction (GJ) [67]

Rhizoma Paridis saponins (RPS) Induces apoptosis via mitochondrial apoptotic pathway [68] Breast Cancer

Polyphyllin D Elicits apoptosis through mitochondria dysfunction. [69, 70]

Gastric Cancer Dioscin Elicits G2/M phase arrest and apoptosis via mitochon-

drial pathway [71]

Tongue squamous cell carcinoma A monomer compound

named as PP-22 Elicits S and G2/M phases arrest and apoptosis via ex-

trinsic apoptotic pathway [72]

inverted repeated regions (IRs: 27,329–28,373 bp) separated by a large single-copy region (LSC: 82,726–85,187 bp) and a small single-copy region (SSC: 17,907–18,671 bp). The 12 genomes contained 115 genes, including 81 protein-coding genes, 4 ribosomal RNA genes, and 30 tRNA genes [84].

The overall cp genomes structure of the 11 Paris taxa was found to be quite similar. After sequencing, the phylo-genetic analyses derived from the complete cp genomes did not resolve the issue of classification of Paris as a mono-phyletic group. However, the work provides evidence sup-porting the division of the 12 taxa into two genera: Paris sensu strict and Daiswa. One of the most important results of this research is the finding of the ten rapidly evolving re-gions that were identified across the cp genomes that could serve as potential DNA barcodes for species identification in Paris sensu strict and Daiswa [84].

12. THREATS AND CONSERVATION

Based on reports of some anticancer potential of the rhi-zomes, P. polyphylla has been unsustainably harvested from the wild of the subtropical forest of Eastern Himalayan re-gions by the local communities. Such unsustainable collec-tion and harvesting practices have pushed the species on the edge of vulnerability [10]. The plant which was abundant in the last decade has decreased drastically. Therefore, conser-

vation of this plant as well as educating the locals on the importance of this plant and its conservation in the region is imperative. The species need to be propagated either through conventional mean in the nursery or through the in vitro technique.

Effective conservation strategies both in situ and ex- situ of this herb need the cooperation of government and non- government organizations, and ordinary local folks to protect the species from its extinction. Spreading awareness about the vulnerability of the plant, its high medicinal properties, economic importance, and getting the involvement of the people from various localities of different countries where the plant thrives could increase its population. Conservation in the higher level could be the inclusion of the species under the priority species list of both at the National and State Me-dicinal Plant Boards for cultivation may be helpful for its long-term management and conservation. Meticulous re-search on exploration, documentation, and identification of its major habitats and distribution regions with the aid of a tool such as ecological niche modeling is required. After having known the appropriate regions or selected areas of a good viable population of this herb, proper legal protection act could be enacted. At present, biotechnological ap-proaches such as clonal propagation of the species through vegetative techniques or through tissue culture are being carried out for the conservation and improvement of the


plant species. When taken out from its natural habitats, the herb grows well with associated plants as found in the wild. This is another possibility for the future conservation of this herb. Associated plants might possibly act as a powerful catalyst for mass multiplication [86].

CONCLUSION

Medicinal plants such as P. polyphylla have drawn much attention in the field of pharmaceutical since they are com-paratively less toxic than synthetic drugs. The bioactive compounds of the herb have significant biological activities such as anticancer, antibacterial, antifungal and antiviral. The compilation of this overview indicates that studies on the herb on classification, phytochemistry, and biological activities are being updated and refined every year. These mentioned research gradually augment the mode of action of the compounds derived from the herb and beacons for further works.

CONSENT FOR PUBLICATION Not applicable.

FUNDING None.

CONFLICT OF INTEREST The authors confirm that this article content has no con-

flict of interest.

ACKNOWLEDGEMENTS Declared none.

REFERENCES [1] Bhakuni, D.S.; Labroo, V.M.; Singh, A.N.; Kapil, R.S. Biosynthe-

sis of the bisbenylisoquinoline alkaloid cocsulin. J.Chem. Soc Perkin. Trans., 1978, 1, 121.

[2] Shah A.S.; Mazumder, P.B.; Choudhury, M.D. Medicinal Proper-ties of Paris polyphylla Smith: A Review. Journal of Herbal Medi-cine and Toxicology, 2012, 6 (1), 27-33.

[3] Long, C.L.; Li, H.; Ouyang, Z.Q.; Yang, X.Y.; Li, Q.; Trangmar, B. Strategies for agrobiodiversity conservation and promotion: a case from Yunnan, China. Biodivers Conserv., 2003, 12, 1145-1156.

[4] Liang, S.Y.; Soukup, V.G.; Paris, L. Flora of China Volume 24 Flagellariceae through Marantaceae. Wu Z.Y, Raven P.H ed.; Beijing, China: Science Press and St Luis, USA: Botanical Garden Press, 2000, 88-95.

[5] Man, S.; Gao, W.; Zhang, Y.; Ma, C.; Yang, L.; and Li, Y. Paridis saponins inhibiting carcinoma growth and metastasis in vitro and in vivo. Archives of Pharmacy Research, 2011, 34(1) 43-50.

[6] Ji, Y.H.; Fritsch, P.W.; Li, H.; Xiao, T.J.; Zhou, Z.K. Phylogeny and classification of Paris (Melanthiaceae) inferred from DNA se-quence data. Ann Bot., 2006, 98, 245–256.

[7] Hara, H. Variations in Paris polyphylla Smith with reference to other Asiatic species. Journal of the faculty of science, University of Tokyo, Sect. 3, Botany, 1969, 10, 141–180

[8] Singh, R.K.I.; Panmei, C.; Devi, L.S.; Shah, S.A.; Devi, K.T.; Devi, Kh. S. Paris polyphylla Smith-The Wonder Herb: In Proceed-ing international conclave on medicinal plants for ASEAN &

BIMSTEC countries, Dec. 11-Dec.13, 2008, 82-86, Imphal, Ma-nipur, India.

[9] Deb, C.R.; Jamir, S.L.; Jamir, N.S. Studies on vegetative and re-productive ecology of Paris polyphylla Smith: A vulnerable me-dicinal plant. American Journal of Plant Sciences, 2015, 6, 2561-2568

[10] Tag, H. Mainstreaming conservation and sustainable use of me-dicinal plant diversity in three Indian States. Final Technical Re-port submitted to UNDP Cell, New Delhi, India: Govt. of India, 2012, 1-124.

[11] Pande, P.C.; Tiwari, L.; Pande, H.C. Ethnoveterinary plants of Uttaranchal- A review. Indian J Tradit Know, 2007, 6, 444-458.

[12] Mall, B.; Gauchan, D.; Chhetri, R.B. An ethnobotanical study of medicinal plants used by ethnic people in Parbat district of western Nepal. Journal of Ethnopharmacology, 2014.

[13] Tiwari, J.K.; Ballabha, R.; Tiwari, P. New York Science Journal, 2010, 3(4), 123-126.

[14] Sharma, A.; Kalita, P.; Tag, H. Distribution and phytomedicinal aspects of Paris polyphylla Smith from the Eastern Himalayan Re-gion: A review. Humanitas Medicine, 2015, 5(3), 15.

[15] Yun, H.; Lijian, C.; Wenhong, Z.; Yuhong, D.; Yongli, W.; Qiang, W.; Ding, Z. Chemistry of Natural products, 2007, 43(6), 672-677.

[16] Lee, M.S.; Yuet-Wa, J.C.; Kong, S.K.; Yu, B.; Eng-Choon, V.O.; Nai-Ching, H.W.; Wai, T.M.; Fung, K.P. Cancer Bio Ther., 2005, 4(11), 1248-1254.

[17] The Pharmacopoeia Committee of China. Chinese Pharmacopoeia 2010 ed., Beijing: The People's Medical Publishing House, 2010, 243–4.

[18] Wu, S.S.; Gao, W.Y.; Duan, H.Q.; Jia, W. Advances in studies on chemical constituents and pharmacological activities of Rhizoma Paridis. Chin Tradit Herb Drugs, 2004, 35, 344–7.

[19] Yan, L.L.; Zhang, Y.J; Gao, W.Y.; Man, S.L. China Journal of Chinese Materia Medica, 2008, 33, 2057.

[20] Chowdhery, H.J.; Giri, G.S.; Pramanik, A. Materials for the Flora of Arunachal Pradesh. Vol. 3. Hydrocharitaceae-Poaceae. Flora of India, Series 2. Botanical Survey of India, Kolkata, India, 2009, 349.

[21] Gogoi, R. The family Liliaceae in Manipur, India. Bull Arunachal Forest Res., 2010, 26, 73-81.

[22] Goraya, G.S.; Jishtu, V.; Rawat, G.S.; Ved, D.K. Wild medicinal plants of Himachal Pradesh: An assessment for their conservation status and management prioritization. Himachal Pradesh Forest Department, Shimla, Himachal Pradesh, India, 2013.

[23] ENVIS. Medicinal plants of conservation concern. ENVIS centre on conservation of medicinal plants, FRLHT, Bangalore, 2010.http://envis.frlht.org/medicinal-plants-conservation-concernspecies.php [accessed January 25 2018].

[24] Lalsangluaii, F.; Chinlampianga, M.; Shukla, A.C. Efficacy and potency of Paris polyphylla Smith, an ethno-medicinal plant of Mizoram. Sci Technol J, 2013, 1, 36-40.

[25] Jamir, N.S.; Lanusunep.; Pongener, N. Medico-herbal medicine practiced by the Naga tribes in the state of Nagaland (India). Indian Fund Appl Life Sci, 2012, 2, 328-333.

[26] Maity, D.; Pradhan, N.; Chauhan, A.S. Flock uses of some medici-nal plants from North Sikkim. Indian J Tradit Know, 2004, 3, 66-71.

[27] Mir, A.H.; Upadhaya, K.; Choudhury, H. Diversity of endemic and threatened ethnomedicinal plant species in Meghalaya, north-east India. Int Res J Environment Sci, 2014, 3, 64-78.

[28] Zhang, M.; Li, Y.W.; Li, Z.Y.; Huang, X.L.; Zhu.; Liu Q.S. Pro-gress on studies of endangered ethno-medicine of Rhizoma Paris. J Cent Univ National (Nat Sci Ed), 2011, 20, 65–9.

[29] Wen, F.; Yin, H.; Chen, C.; Liu, X.; Xue, D.; Chen, T.; He, J.; Zhang, H. Chemical characteristics of saponins from Paris fargesii var. brevipetala and cytotoxic activity of its main ingredient, paris saponin H. Fitoterapia, 2012, 83, 627–635.

[30] Jianjun, Qi.; Zheng, Na.; Zhang, B.; Sun, P.; Hu, S.; Xu, W.; Ma, Q.; Zhao, T.; Zhou, L.; Qin M.; Xianen, L. Mining genes involved in the stratification of Paris polyphylla seeds using high-throughput embryo transcriptome sequencing. BMC Genomics, 2013, 14, 358.

[31] Jamir, S.L.; Jamir, N.S.; Deb, C.R. Production of clonal planting material and propagation of Paris polyphylla Smith var. polyphylla through rhizome splitting. European Journals of Biotechnology and Bioscience, 2015, Volume: 3, Issue: 9, 43-46.

[32] Danu, K.; Singh, A.R.; Pande, V.; Kumar, SM.; Rawal, P. Vegeta-tive propagation of an endangered medicinal plant of Himalayan


region, Paris polyphylla Smith. International Journal of Current Microbiology and Applied Sciences, 2015, 4 (6), 660-665.

[33] Shiveirou, R.; Kumaria, S.; Tandon, P. Plant regeneration through direct somatic embryogenesis from immature zygotic embryos of the medicinal plant, Paris polyphylla Sm. Plant Cell, Tissue and Organ Culture (PCTOC). 2014, 118 (3), 445–455

[34] Shiveirou, R.; Kumaria, S.; Kehie, M.; Pramod T. Plantlet regen-eration of Paris polyphylla Sm. via thin cell layer culture and en-hancement of steroidal saponins in mini-rhizome cultures using elicitors. Springer Netherlands, 2015, 341-353.

[35] Rajsekhar, P.B.; Bharani, A.R.S.; Angel, K.J.; Ramachandran, M.; Priya, S.; Rajsekhar,V. Extraction of Paris polyphylla rhizome using different solvents and its phytochemical studies. International Journal of Pharmacognosy and Phytochemical Research, 2016, 8(1), 18-21.

[36] Fu, Y.L.; Zhao, Z.H.; Shan, Y.J.; Cong, Y.W. Inducing effect of total steroid saponins from Paris polyphylla on platelet aggregation in vitro and its potential mechanism. Bulletin Academy Military Med Sci., 2007, 31, 416-419.

[37] Tang, H.F.; Zhao, Y.P. Research survey of plants of Paris L. Chin Trad Herb Drugs, 1998, 12: 839–42.

[38] Pande, P.C.; Tiwari, L.; Pande, H.C. Ethnoveterinary plants of Uttaranchal- A review. Indian J Tradit Know., 2007, 6, 444-458.

[39] Devkota, K.P. Bioprospecting studies on Sarcococca hookeriana Bail, Sonchus wightianus DC, Paris polyphylla Smith and related Medicinal Herbs of Nepal: Ph D Thesis, HEJ Research Institute of Chemistry, International Centre for Chemical Science, University of Karachi: Karachi-75270, Pakistan, 2005.

[40] Zhao, Y.; Kang, L.P.; Liu, Y.X.; Zhao, Y.; Xiong, C.Q.; Ma, B.P.; Dong, F.T. Three new steroidal saponins from the rhizome of Paris polyphylla. Magnetic Resonance in Chemistry, 2007, 45, 739–744.

[41] Zhao, Y.; Kang, L.P.; Liu, Y.X.; Liang, Y.G.; Tan, D.W.; Yu, Z.Y.; Cong, Y.W.; Ma, B.P. Steroidal saponins from the rhizome of Paris polyphylla and their cytotoxic activities. Planta Med., 2009, 75, 356–363.

[42] Jin, L.Y.; Lu, T.X.; Qin, X.J.; Ni, W.; Yan, H.; Chen, Y.; Liu, H.; He, H.P.; Liu, H.Y. Two new highly oxygenated spirostanol sapon-ins from Paris polyphylla var. stenophylla. Nat. Prod. Bioprospect., 2016.

[43] Wei, J.C.; Gao, W.Y.; Yan, X.D.; Wang, Y.; Jing, S.S.; Xiao, PG. Chemical constituents of plants from the Genus Paris. Chemistry and Biodiversity, 2014, 11, 1277.

[44] Lin, Z.; Liu, Y.; Li, F.; Wu, J.; Zhang, G.; Wang, Y.; Lu, L.; Liu, Z. Anti-lung cancer effects of polyphyllin VI and VII potentially correlate with apoptosis in vitro and in vivo. Phytotherapy Re-search, 2015, 29, 1568–1576.

[45] Yu, Q.; Li, Q.; Lu, P.; Chen, Q. Polyphyllin D induces apoptosis in U87 human glioma cells through the c-jun NH2-terminal kinase pathway. Journal of Medicinal J. Med Food, 2014, 17 (9), 1036–1042.

[46] Yue, G.; Wei, J.; Qian, X.; Yu, L.; Zou, Z.; Guan, W.; Wang, H.; Shen, J.; Liu, B. Synergistic anticancer effects of polyphyllin I and evodiamine on freshly-removed human gastric tumors. PLoS One, 2013, 8, e65164.

[47] Xiao, X.; Zo, J.; Bui-Nguyen, T.M.; Bai, P.; Gao, L.; Liu. J.; Liu, S.; Xiao, J.; Chen, X.; Zhang, X.; Wang. H. Paris saponin II of rhi-zoma paridis – A novel inducer of apoptosis in human ovarian can-cer cells. BioScience Trends, 2012, 6(4), 201-211.

[48] Zhang, W.; Zhang, D.; Ma, X.; Liu, Z.; Li, F.; Wu, D. Paris saponin VII suppressed the growth of human cervical cancer Hela cells. J Med Res, 2014, 19, 41.

[49] Qin, XJ.; Sun, DJ.; Ni, W.; Chen, CX.; Hua, Y.; He, L.; Liu, HY. Steroidal saponins from stems and leaves of Paris polyphylla var.yunnanensis. Steroids, 2012, 77, 1242–1248.

[50] Qin, X.J.; Chen, C.X, Ni, W.; Yan, H.; Liu, H.Y. C22-steroidal lactone glycosides from stems and leaves of Paris polyphylla var. yunnanensis. Fitoterapia, 2013, 84, 248–251.

[51] Fu Y.L.; Zhao, Z.H.; Shan, Y.J.; Cong, Y.W. Inducing effect of total steroid saponins from Paris polyphylla on platelet aggregation in vitro and its potential mechanism. Bulletin Academy Military Med Sci, 2007, 31, 416-419.

[52] GuangLie, C.; WeiShi, G.; GaiLing, H.; JianPing, C. Effect of paris saponin on antitumor and immune function in U14 tumor-bearing mice. Afr J Tradit Complement Altern Med., 2013, 10, 503-507.

[53] Man, S.; Gao, W.; Zhang, Y.; Ma, C.; Yangm K,; Li, Y. Paridis saponins inhibiting carcinoma growth and metastasis in vitro and in vivo. Arch Pharm Res., 2011, 34 (1), 43-50.

[54] Song, L.; Hong, X.; Ding, Z. Paris plants. In: Modern Grand Dic-tionary of Chinese Materia Medica. Beijing: People’s Sanitation Press, 2001, 1619–22.

[55] Wang, Y.; Zhang, Y.; Zhu, Z. Exploration of the correlation be-tween the structure, hemolytic activity, and cytotoxicity of steroid saponins. Bioorg Med Chem., 2007, 15(7), 2528–2532.

[56] Zhang, L.T.; Zuo, Y.T.; Gao, W.Y. Anti-tumor effects of extracts and chemical constituents from Paris polyphylla var yunnanensis. Chin Trad Herb Drugs, 2007, 38, 422–4.

[57] Bachran, C.; Sutherland, M.; Heisler, I.; Hebestreit, P.; Melziq, M.F.; Fuchs, H. The saponin mediated enhanced uptake of targeted saporin-based drugs is strongly dependent on the saponin structure. Exp Biol Med., 2006, 231(4), 412–20.

[58] Brouxhon. S.M.; Kyrkanides, S.; Raja, V.; Silberfeld, A.; Teng, XF.; Trochesset, D. Ectodomain-specific E-cadherin antibody suppresses skin SCC growth and reduces tumor grade: A multi-targeted therapy modulating RTKs and the PTEN-p53-MDM2 Axis. Mol Cancer Ther., 2014, 13(7), 791–802.

[59] Zhang, C.; Jia, X.; Bao, J.; Chen, S.; Wang, K.; Zhang, Y.; Li, P.; Wan, J.Bo.; Su, H.; Wang, Y.; Mei, Z.; He, C. Polyphyllin VII in-duces apoptosis in HepG2 cells through ROS-mediated mitochon-drial dysfunction and MAPK pathways. BMC Complementary and Alternative Medicine, 2016, 16, 58.

[60] Qi, Y.; Chen, X.; Chan, C.; Li, D.; Yuan, C.; Yu, F.; Lin, M.C.; Yew, D.T.; Kung, H.F.; Lai, L. Two-dimensional differential gel electrophoresis/analysis of diethylnitrosamine induced rat hepato-cellular carcinoma. Int. J. Cancer, 2008, 122, 2682–2688.

[61] Tan, Y.; Yin, P.; Tang, L.; Xing, W.; Huang, Q.; Cao, D.; Zhao, X.; Wang, W.; Lu, X.; Xu, Z.; Wang, H,; Xu, G. Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis. Mol. Cell. Proteomics, 2012, 11, 1–12.

[62] Liu, J.; Man, S.; Li, J.; Zhang, Y.; Meng, X.; Gao, W. Inhibition of diethylnitrosamine-induced liver cancer in rats by Rhizoma paridis saponin. Environmental Toxicology and Pharmacology, 2016, 46, 103–109.

[63] Man, S.; Gao, W.; Zhang, Y.; Ma, C.; Yang.; Li, Y. Paridis sapon-ins inhibiting carcinoma growth and metastasis in vitro and in vivo. Archives of Pharmacy Research, 2010, 34 (1), 43-50.

[64] Ruamrungsri, N.; Siengdee, P.; Sringarm, K.; Chomdej, S.; Ong-chai, S.; Nganvongpanit, K. In vitro cytotoxic screening of 31 crude extracts of Thai herbs on a chondrosarcoma cell line and primary chondrocytes and apoptotic effects of selected extracts. In Vitro Cell. Dev. Biol.—Animal, 2016.

[65] Wang, C.W.; Tai, C.J.; Choong, C.Y.; Lin, Y.C.; Lee, B.H.; Shi, Y.C.; Tai, C.J. Aqueous extract of Paris polyphylla (AEPP) inhibits ovarian cancer via suppression of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha. Molecules, 2016, 21, 727.

[66] Yang, C.; Cai, H.; Meng, X. Polyphyllin D induces apoptosis and differentiation in K562 human leukemia cells. International Im-munopharmacology, 2016, 36, 17-22.

[67] Li, F.R.; Jiao, P.; Yao, S.T.; Sang, H.; Qin, S.C.; Zhang, W.; Zhang, Y.B.; Gao, L.L. Paris polyphylla Smith extract induces apoptosis and activates cancer suppressor gene connexin26 expres-sion. Asia Pac J Cancer Prev., 2012, 13, 205-209.

[68] Lu, C.; Li, C.J.; Wu, D.; Lu, J.M.; Tu, F.; Wang, L. Induction of apoptosis by rhizoma paridis saponins in MCF-7 human breast cancer cells. African Journal of Pharmacy and Pharmacology, 2011, 5(8), 1086-1091.

[69] Lee, M.S.; Chan, J.Y.W.; Kong, S.K.; Yu, B.; Eng-Choon, V.O.; Nai-Ching, H.W.; Chung-Wai, T.M.; Fung, K.P. Effects of poly-phyllin D, a steroidal saponin in Paris polyphylla, in growth inhibi-tion of human breast cancer cells and in xenograft. Cancer Biology & Therapy, 2005, 4 (11), 1248–1254.

[70] Cozzi P. The discovery of a new potential anticancer drug: A case history. Farmaco, 2003, 58, 213-20.

[71] Gao, L.L.; Li, F.R.; Jiao, P.; Yang, M.F.; Zhou, X.J.; Si, Y.H.; Jiang, W.J.; Zheng, T.T. Paris chinensis dioscin induces G2/M cell cycle arrest and apoptosis in human gastric cancer SGC-7901 cells. World Journal of Gastroenterol., 2011, 17(39), 4389-4395.

[72] Ke1, J.Y.; Zhang, W.; Gong, R.S.; Cen, W.J.; Huang, H.Q.; Li, Y.R.; Kong, W.D.; Jiang, J.W. A monomer purified from Paris


polyphylla (PP-22) triggers S and G2/M phase arrest and apoptosis in human tongue squamous cell carcinoma SCC-15 by activating the p38/cdc25/cdc2 and caspase 8/caspase 3 pathways. Tumor Biol., 2016, 37, 14863–14872.

[73] Zhao, J.; Mou, Y.; Shan, T.; Li, Y.; Zhou, L.; Wang, M.; Wang, J. Antimicrobial metabolites from the endophytic fungus Pichia guilliermondii isolated from Paris polyphylla var. yunnanensis. Molecules, 2010, 15, 7961-7970.

[74] Wang, Y.C.; Yi, T.Y. In vitro activity of Paris polyphylla Smith against Enterovirus 71 and Coxsackievirus B3 and its immune modulation. The American Journal of Chinese Medicine, 2011, 39 (6), 1219–1234.

[75] Schrager, S. Abnormal uterine bleeding associated with hormonal contraception. Am Fam Physician, 2002, 65, 2073–2080.

[76] Yua, Z.Y.; Guoa, L.; Wangb, B.; Kangc, L.P.; Zhaoa, Z.H.; Shan, Y.J.; Xiaod, H.; Chena, J.P.; Mac, B.P.; Wen, Y. Structural re-quirement of spirostanol glycosides for rat uterine contractility and mode of their synergism. Journal of Pharmacy and Pharmacology, 2010, 62, 521–529

[77] Li, Y. Studies on the introduction cultivation of genus Paris L. I. A premilinary report on sexual propogation of Paris polyphylla var. yunnanensis. Acta Bot. Yunnanica, 1982, 4, 429–431.

[78] Ling, LZ.; Zhang, S.D.; Zhao, Fan.; Yang, J.L.; Song, W.H.; Guan, S.M.; Li, X.S.; Huang, Z.J.; Cheng, Le. Transcriptome-wide identi-fication and prediction of miRNAs and their targets in Paris poly-phylla var. yunnanensis by high-throughput sequencing analysis. International Journal of Molecular Science, 2017, 18, 219.

[79] Jones-Rhoades, M.W.; Bartel, D.P.; Bartel, B. MicroRNAs and their regulatory roles in plants. Ann. Rev. Plant Biol., 2006, 57, 19-53.

[80] He, L.; Hannon, G.J. MicroRNAs: Small RNAs with a big role in gene regulation. Nat. Rev. Genet., 2004, 5, 522-531.

[81] Jeong, D.H.; Park, S.; Zhai, J.; Gurazada, S.G.; de Paoli, E.; Mey-ers, B.C.; Green, P.J. Massive analysis of rice small RNAs: Mechanistic implications of regulated microRNAs and variants for differential target RNA cleavage. Plant Cell, 2011, 23, 4185-4207.

[82] Ruhsam, M.; Rai, H.S.; Mathews, S.; Ross, T.G.; Graham, S.W.; Raubeson, L.A. Does complete plastid genome sequencing improve species discrimination and phylogenetic resolution in in Araucaria? Mol. Ecol. Resour., 2015, 15, 1067–1078.

[83] Yang, J.B.; Tang, M.; Li, H.T.; Zhang, Z.R.; Li, D.Z. Complete chloroplast genome of the genus Cymbidium: lights into the spe-cies identification, phylogenetic implications and population ge-netic analyses. BMC Evol. Biol., 2013, 13, 1.

[84] Huang, Y.; Li, X.; Yang, Z.; Yang, C.; Yang, J.; Ji, Y. Analysis of complete chloroplast genome sequences improves phylogenetic resolution in Paris (Melanthiaceae). Frontiers in Plant Science, 2016, 7, 1797.

[85] Do, H.D.K.; Kim, J.S.; Kim, J.H. A trnI_CAU triplication event in the complete chloroplast genome of Paris verticillata M. Bieb. (Melanthiaceae, Liliales). Genome Biol. Evol., 2014, 6, 1699–1706.

[86] Paul, Ashish.; Gajurel, P.R.; Das, A.K. Threats and conservation of Paris polyphylla an endangered, highly exploited medicinal plant in the Indian Himalayan Region. Biodiversitas, 2016, 16 (2), 295-302.

an overview of paris polyphylla, a highly vulnerable medicinal...

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