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Paris Polyphylla SM. (Family: Melanthiaceae): The Most Important Himalayan Medicinal Plant
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Paris polyphylla. is a traditional medicinal herb that has long been used to prevent cancer in many Asian countries. Polyphyllin I (PPI), an important bioactive constituent of Paris polyphylla, has been found to exhibit a wide variety of anticancer activities in many types of cancer cells. However, the effects of PPI on human gastric carcinoma cells and its mechanism of action remain unclear. In this study, we examined the effective anti-gastric carcinoma activity of PPI and its underlying mechanism of action in HGC-27 cells. In vitro, sub-micromolar concentrations of PPI inhibited HGC-27 cell proliferation with an IC50 of 0.34 ± 0.06 μM after a 72-h treatment. In vivo, 3 mg/kg PPI significantly inhibited proliferation of HGC-27 tumor cells, with a 78.8% inhibition rate compared to paclitaxel, and demonstrated higher safety. Analysis of MDC and mGFP-LC3 fluorescence, Western blotting and flow cytometry indicated that PPI induced cell cycle arrest in HGC-27 cells by promoting the conversion of LC3-I to LC3-II and by downregulating cyclin B1. Furthermore, Western blotting showed that PPI inhibited the autophagy-regulating PDK1/Akt/mTOR signaling pathway in vitro and in vivo. In addition, immunohistochemistry and TUNEL staining revealed that PPI decreased Ki67 expression and increased the percentage of apoptotic cells in HGC-27 xenograft tumors. These data indicate that PPI is an PDK1/Akt/mTOR signaling inhibitor and of therapeutic relevance for gastric cancer treatment and that the rhizome of Paris polyphylla deserves further clinical investigation as an alternative therapy for gastric cancer.
The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) indicates poor prognosis and promotes EMT and metastasis. EMT, a crucial cellular process that occurs during cancer progression and metastasis, has been reported to promote drug resistance in several previous studies. Consequently, ongoing research has been focused on exploring therapeutic options for preventing EMT to delay or reverse drug resistance. Polyphyllin I (PPI) is a natural component extracted from Paris polyphylla that displays anti-cancer properties. In the present study, we investigated whether PPI can be used in the cisplatin (DDP)-resistant human gastric cancer cell line SGC7901/DDP. The results demonstrated that PPI treatment significantly inhibited cell proliferation, invasion and EMT. TGF-β1 is known to promote EMT-induced metastasis in numerous tumor types. PPI inhibited the invasion of TGFβ1-induced SGC7901/DDP cells in vitro. PPI also increased the mRNA and protein expression levels of E-cadherin but decreased the expression levels of vimentin. Further examination of the mechanism revealed that the CIP2A/PP2A/Akt pathway is partially involved in this regulation of EMT-related biomarkers and invasion. Furthermore, xenograft tests also confirmed the antitumor effects of PPI in vivo. We propose that PPI could be developed as a candidate drug for treating cancer invasion and migration.
India, consisting of 15 agro climatic zones, has got a rich heritage of medicinal plants, being used in various folk and other systems of medicine, like Ayurveda, Siddha, Unani and Homoeopathy. However, in growing world herbal market India’s share is negligible mainly because of inadequate investment in this sector in terms of research and validation of our old heritage knowledge in the light of modern science. Paris polyphylla Smith, a significant species of the genus, has been called as ‘jack of all trades’ owing its properties of curing a number of diseases from diarrhoea to cancer. The present paper reviews the folk and traditional uses of the numerous varieties Paris polyphylla along with the pharmacological value. This may help the researchers especially in India to think about the efficacy and potency of this wonder herb. Due to the importance at commercial level, the rhizomes of this herb are illegally traded out of Indian borders. This illegal exploitation of the species poses a grave danger of extinction of its population if proper steps are not taken for its conservation. Both in situ and ex situ effective conservation strategies may help the protection of this species as it is at the brink of its extinction.
PurposeNeuroblastoma is a refractory pediatric malignant solid tumor. The previous studies demonstrated that Polyphyllin D, the main constituent of Paris polyphylla, a traditional Chinese medicine, exerts an anti-tumor effect on many tumors. However, its effects against neuroblastomas are unclear. Methods
We examined the anti-tumor effect of polyphyllin D in human neuroblastoma using IMR-32 and LA-N-2 cells, which exhibit MYCN gene amplification, and NB-69 cells, which do not exhibit MYCN gene amplification. ResultsAll cell lines showed reduced cell viability in response to polyphyllin D treatment. No caspase-3/-7, -8, and -9 activity was observed in IMR-32 and LA-N-2 cells treated with polyphyllin D. In contrast, activation of caspase-3/-7, and -8 activity was observed in NB-69 cells. When polyphyllin D and specific inhibitors of RIPK3 involved in necroptosis were added to IMR-32 and LA-N-2 cell lines, polyphyllin D-induced cell death was inhibited. Conclusion
Together, this indicates that the underlying mechanism of polyphyllin D-induced cell death in NB-69 cells is apoptosis, whereas the cell death of IMR-32 and LA-N-2 cells occurs by necroptosis. We continue research on this topic and look forward the discovery of a new therapeutic agent for neuroblastoma.
Plants play a vital role in the healthcare of the local tribal people in Meghalaya. A number of species are used for curing a wide range of ailments. Traditional remedies are part of the cultural and spiritual life of these people. The objective of the study was to evaluate the diversity and role of endemic and threatened plant species in ethnomedicine. A total of 131species, including 36 endemic and 113 species under different threat categories were found. This includes 73 and 46 species that falls under different degrees of threats at regional and global levels respectively. The life form of these plants can be arranged in the order of trees>herbs>shrubs>climbers>epiphytes. It was also found that the indigenous community holds substantial knowledge on ethnomedicinal plants that plays an important role in assisting the primary healthcare needs of the people. These plants would be of much benefit, if evaluated and introduced in the modern scientific health care system. However, the decline in population due to overharvesting and habitat destruction of these plants calls
for necessary measures for their effective conservation.
Comparative studies have established that the North-Eastern (NE) region of India which is a part of the Eastern Himalayan region is affluent in both traditional knowledge based phytomedicine and biodiversity. About 1953 ethno-medicinal plants are detailed from the NE region of India out of which 1400 species are employed both as food and ethnopharmacological resources. Nearly 70% of species diversity has been reported from the two Indian biodiversity hotspots-The Western Ghats and the Eastern Himalayas and these hotspots are protected by tribal communities and their ancient traditional knowledge system. Paris polyphylla Smith belongs to the family Melanthiaceae and is a traditional medicinal herb which is known to cure some major ailments such as different types of Cancer, Alzheimer's disease, abnormal uterine bleeding, leishmaniasis etc. The major phytoconstituents are dioscin, polyphyllin D, and balanitin 7. Phylogeny of Paris was inferred from nuclear ITS and plastid psbA-trnH and trnL-trnF DNA sequence data. Results indicated that Paris is monophyletic in all analyses. Rhizoma Paridis, which is the dried rhizome of Paris polyphylla is mainly used in Traditional Chinese Medicine and its mode of action is known for only a few cancer cell lines. The current review determines to sketch an extensive picture of the potency, diversity, distribution and efficacy of Paris polyphylla from the Eastern Himalayan region and the future validation of its phytotherapeutical and molecular attributes by recognizing the Intellectual Property Rights of the Traditional Knowledge holders.
The root of Paris polyphylla (RPP) is widely used as a traditional Chinese medicine for a long time due to the good properties of heat-clearing and detoxicating, detumescence, sedation, acesodyne and haemostasis. To clarify on the bioactive substances and ensure the safety in clinical medication, a feasible and accurate strategy was developed by applying the high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight-mass spectrometry (HPLC-ESI-QTOF-MS/MS). Separation was performed an Agilent poroshell 120 EC-C18 column (2.7 × 100 mm, i.d., 2.7 μm) with 0.1% formic acid aqueous solution and acetonitrile as the mobile phase under gradient conditions. Based on the proposed strategy, 30 constituents, mainly including steroidal saponins, were characterised or tentatively identified, 2 of which were the first to be reported as the potential new steroidal saponins in RPP. In conclusion, the HPLC-ESI-QTOF-MS/MS is a feasible and credible technique to separate and identify steroidal saponins from botanical extracts.
Background
Saponins of several herbs are known to induce apoptosis in many cancer cells. The present study aimed to investigate the growth inhibitory effect of Paris saponin VII (PS VII), a kind of steroidal saponins from Chonglou (Rhizoma Paridis Chonglou), on the human cervical cancer cell line Hela and the relative molecular mechanisms.
Methods
Hela cells were exposed to different concentrations of PS VII (1 to 100 μM). Inhibition of cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-ethynyl-2′-deoxyuridine (EdU) assays. The amount of apoptotic cells was evaluated by flow cytometric analysis. And the protein level of cleaved caspase-3, cleaved caspase-9, Bax, and Bcl-2 was evaluated by Western blot.
Results
The half maximal inhibitory concentration (IC50) value of PS VII for the growth inhibition of Hela cells was 2.62 ± 0.11 μM. PS VII increased the expression of caspase-3, caspase-9, and Bax while decreased that of Bcl-2, suggesting that PS VII may induce apoptosis through intrinsic apoptotic ways.
Conclusions
These data indicate that PS VII has the potential for the treatment of cervical cancer.
To study the anticancer mechanism of polyphyllin I (PPI), a Traditional Chinese Medicine, on the ovarian cancer cell line HO-8910PM in vitro.
Transwell chamber invasive assays were used to investigate the inhibitory capacity of PPI on HO-8910PM metastasis. Gene expression profiling chips was used to screen differentially expressed genes between experiment group and control group. Reverse transcription PCR and Western blotting were used to determine mRNA and protein levels.
With increasing PPI concentration, the metastatic capacity of cells decreased, with significance differences between the experimental and control groups (P < 0.01) as well as between two concentration groups. Gene expression profiling identified 123 differentially expressed genes, of which 70 were downregulated and 53 were upregulated. The genes were involved in multiple signal transduction pathways, including apoptosis, proliferation and metastasis. Real-time PCR (RT-PCR) showed that differential genes PIK3C2B, Caspase 9 and Wnt5A were downregulated with increasing PPI, showing an evident dose-effect relationship. The c-Jun was an exception. As the PPI dosage increased and the exposure time was extended, c-Jun relative expression showed an upward trend. There were significant differences between the experiment and control (P < 0.05). Western blot analyses showed that PPI treatment decreased levels of Caspase 9, Wnt5A and PIK3C2B and increased activated Caspase 9, c-Jun and p-c-Jun expression levels.
PPI has strong antitumor and anti transfer activity. It can activate c-Jun expression and the JNK signaling pathway, elicit cell apoptosis via the mitochondrial-mediated Caspase activation pathway, and finally inhibit tumor growth and migration in vitro. The downregulation of PIK3C2B and Wnt5A jointly inhibit the proliferation and metastasis of HO-8910PM. PPI may be a novel treatment for ovarian cancer.
To evaluate in vitro antimicrobial activities of selected 58 ethno-medicinal plant extracts with a view to assess their therapeutic potential.
A total of 58 traditional Chinese medicinal plants were carefully selected based on the literature review and their traditional use. The antimicrobial activities of ethanol extracts of these medicinal plants were tested against fungi (Aspergillus fumigatus), yeast (Candida albicans), gram-negative (Acinetobacter baumannii and Pseudomonas aeruginosa) and gram-positive bacteria (Staphylococcus aureus). The activities were tested at three different concentrations of 1.00, 0.10 and 0.01 mg/mL. The data was analysed using Gene data Screener program.
The measured antimicrobial activities indicated that out of the 58 plant extracts, 15 extracts showed anti-fungal activity and 23 extracts exhibited anti-bacterial activity. Eight plant extracts have exhibited both anti-bacterial and anti-fungal activities. For instance, Eucommia ulmoides, Polygonum cuspidatum, Poria cocos and Uncaria rhyncophylla showed activity against both bacterial and fungal strains, indicating their broad spectrum of activity.
The results revealed that the ethanol extracts of 30 plants out of the selected 58 possess significant antimicrobial activities. It is interesting to note that the findings from the current study are consistent with the traditional use. A clear correlation has also been found between the antimicrobial activity and the flavonoid content of the plant extracts which is in agreement with the literature. Hence, the results presented here can be used to guide the selection of potential plant species for the isolation and structure elucidation of novel antimicrobial compounds in order to establish the structure-activity relationship. This in turn is expected to lead the way to the discovery of novel antimicrobial agents for therapeutic use.
Further phytochemical investigation on the stems and leaves of Paris polyphylla var. yunnanensis led to the isolation of three C(22)-steroidal lactone glycosides. Two of these are new compounds, designated as chonglouoside SL-7 (1) and chonglouoside SL-8 (2). Their structures were elucidated on the basis of extensive spectroscopic analysis, as well as comparison with the reported spectroscopic data. This is the first report of C(22)-steroidal lactone glycosides isolated from the Paris genus. Compounds 1 and 3 showed moderate antimicrobic activity against Propionibacterium acnes with MIC values of 31.3 and 3.9μg/mL, respectively.
Background
The main aim of this study is to evaluate the antioxidant and anti-inflammatory properties of forty four traditional Chinese medicinal herbal extracts and to examine these activities in relation to their antioxidant content.
Methods
The antioxidant activities were investigated using DPPH radical scavenging method and yeast model. The anti-inflammatory properties of the herbal extracts were evaluated by measuring their ability to inhibit the production of nitric oxide and TNF-α in RAW 264.7 macrophages activated by LPS and IFN- γ, respectively. The cytotoxic effects of the herbal extracts were determined by Alomar Blue assay by measuring cell viability. In order to understand the variation of antioxidant activities of herbal extracts with their antioxidant contents, the total phenolics, total flavonoids and trace metal (Mg, Mn, Cu, Zn, Se and Mo) quantities were estimated and a correlation analysis was carried out.
Results
Results of this study show that significant levels of phenolics, flavonoids and trace metal contents were found in Ligustrum lucidum, Paeonia suffuticosa, Salvia miltiorrhiza, Sanguisorba officinalis, Spatholobus suberectus, Tussilago farfara and Uncaria rhyncophylla, which correlated well with their antioxidant and anti-inflammatory activities. Some of the plants displayed high antioxidant and anti-inflammatory activities but contained low levels of phenolics and flavonoids. Interestingly, these plants contained significant levels of trace metals (such as Zn, Mg and Se) which are likely to be responsible for their activities.
Conclusions
The results indicate that the phenolics, flavonoids and trace metals play an important role in the antioxidant activities of medicinal plants. Many of the plants studied here have been identified as potential sources of new antioxidant compounds.
India has a rich heritage and long history of using medicinal plants for
improving the quality of life. India’s plant bio-diversity is one of the richest in the
world and estimated to have 43000 of the plant species growing on this earth. However,
India’s share in the growing world herbal market is negligible mainly because of
inadequate investment in this sector in terms of research and validation of our old
heritage knowledge in the light of modern science. Paris polyphylla Smith an important
member of this genus can be truely called ‘jack of all trades’ with its properties of
curing a number of diseases from diarrhoea to cancer. The present paper enumerates
the folk & traditional value of the plants along with the pharmacological value which
may help the researchers to set their minds for approaching the utility, efficacy and
potency of Paris polyphylla Smith.
Paris species are perennial rhizomatous herbs. A grown plant (Fig. 2.1) comprises adventitious roots, rhizome, stem, leaves, and flower (fruit and seeds). The rhizome grows underground, bearing many adventitious roots and one or several apical buds. The aerial organs (stem, leaves, and flower) die each winter, and underground rhizome produces new shoots in the next spring. After dormancy, the aerial stem withers, which forms a scar on the rhizome. Based on the number of scars on the rhizome, it is easy to estimate the approximate age of the plant. The stem of Paris species is erect, cylindrical, and smooth or pubescent. A whorl of 4–15 net-veined leaves and a solitary flower develop at the stem apex; these characters are highly distinctive in angiosperms (Hara 1969; Li 1998). Flowers of Paris species are bisexual and mostly 4- to15-merous. Compared with the trimerous condition of Trillium Linn. (Fig. 2.2), a sister genus of Paris, the floral and phyllotaxy merosity are likely the morphological synapomorphies that differentiate the two genera.
Polyphyllin I (PPI), an extract from Paris polyphylla, has been demonstrated to possess antitumor activity against multiple cancers. However, whether PPI can inhibit bladder cancer (BCa) and the underlying mechanisms have never been researched. In this study, we initially found that PPI could induce BCa cell apoptosis and cell cycle arrest, as well as inhibit cell proliferation in vitro. Additionally, PPI could effectively suppress the in vivo growth of BCa in the xenograft mice model. Furthermore, we found that forkhead box O3 (FOXO3) and its targets including BIM or NOXA were significantly upregulated in BCa cells following PPI treatment. Interestingly, we observed that FOXO3 knockdown partly reversed the effects of PPI on BCa cells. Taken together, our findings suggested that PPI exerted a cytotoxic effect in vitro and an antitumor activity in vivo against BCa partly by activating FOXO3 signaling pathway. Therefore, PPI may serve as a promising chemotherapy agent for BCa treatment.
Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide. Accumulating evidence suggests that mitochondrial dynamics are closely implicated in carcinogenesis including CRC. Paris Saponin II (PSII), a major steroidal saponin extracted from Rhizoma Paris polyphylla, has emerged as a potential anticancer agent. However, the effects of PSII on CRC and its underlying mechanisms remain unknown. In the present study, we found PSII induced apoptosis and inhibited colony formation in HT 29 and HCT 116 cells, and cell cycle arrest in G1 phase. PSII inhibited the phosphorylation of ERK1/2 and mitochondrial translocation of dynamin-related protein 1 (Drp1) by dephosphorylating Drp1 at Ser616, leading to the suppression of mitochondrial fission. PSII also suppressed NF-κB activation as a result of the inhibition of IKKβ and p65 translocation. Drp1 knockdown remarkably downregulated the nuclear expression of p65 and its target genes cyclin D1 and c-Myc in HCT 116 cell, confirming the link between mitochondrial fission and NF-κB pathway. Silencing of Drp 1 enhanced the inhibitory effects of PSII on p65 phosphorylation and the expressions of cyclin D1 and c-Myc, revealing that the inhibitory effects of PSII on cyclin D1 and c-Myc were relevant in the suppression of Drp1 and NF-κB activation. An in vivo study demonstrated PSII remarkably decreased the xenograft tumor size and suppressed the phosphorylation of ERK1/2 and Drp1 at Ser616. Taken together, our results suggested that PSII could inhibit colorectal carcinogenesis, at least in part, by regulating mitochondrial fission and NF-κB pathway.
The aim of this study was to identify the anti-cancer mechanism of Polyphyllin I (PPI) on gastric cancer cells via its activity on cancer-associated fibroblasts (CAFs). We cultured purified gastric CAFs obtained from fresh human gastric cancer tissue and examined the effect of Polyphyllin I on CAF proliferation using a colorimetric viability assay. In addition, we established a nude mouse xenograft model to examine the effect of Polyphyllin I administration on tumorigenesis. Using Western analysis, we quantified protein expression of the CAF-derived cytokines fibroblast activation protein alpha (FAP), secreted protein acidic and cysteine rich (SPARC), stromal cell-derived factor 1 (SDF-1), hepatocyte growth factor tenascin-C (TNC), and hepatocyte growth factor (HGF) in both in vitro and in vivo models. We found that Polyphyllin I inhibits the proliferation of CAFs in a concentration-dependent manner. Following treatment with 2 μg/ml PPI for 24 h in vitro, the expression of FAP, SDF-1 and HGF protein in CAFs was significantly lower than that in the control group, but there was no significant difference in SPARC and TNC protein expression between the two groups. In the nude mouse xenograft model, the tumor inhibition rate was 45.5% when PPI was administered early and 29.4% with administration in the third week. The expression of FAP and HGF in the xenografts was significantly decreased, while the expression of SPARC, SDF-1, and TNC was largely unaltered. Altogether, these data suggest that Polyphyllin I can inhibit the proliferation of gastric cancer cells by downregulating the expression of FAP and HGF in CAFs in vivo.
To optimize the use of Paris polyphylla resources, a homogenous polysaccharide (PPLP) was obtained from P. polyphylla leaves. Its average molecule weight was 2.95×10(4)Da, and the analysis of monosaccharide composition shown that PPLP consisted of l-arabinose and d-galactose with a molar ratio of 4.2:5.8. Methylation and nuclear magnetic resonance (NMR) spectroscopy data revealed that the backbone of PPLP was comprised of (1→6)-β-d-galactan, and the branched chains mainly consisted of arabinosyl residues which was linked to backbone via (1→3)-linkages. In addition, the antiaging effect of PPLP was investigated in a d-galactose induced mouse aging model. Compared with model group, the formations of malondialdehyde (MDA) were significantly prevented, and the levels of antioxidant enzymes and total antioxidant capacity (TAOC) were significantly improved in serum and liver in PPLP dose groups. These results demonstrated that PPLP possessed potent antiaging capacity.
Polyphyllin Ι is a steroidal saponin isolated from the rhizoma of Paris polyphylla. In the present study, we aimed to investigate the anticancer effects of polyphyllin Ι in colorectal cancer and to elucidate the potential underlying molecular mechanisms. Using, CCK8 assay, flow cytometry, laser confocal microscope analysis and western blot, the anticancer effects of the polyphyllin Ι were analysed in colorectal cells. Our results indicate that polyphyllin Ι significantly decreased cell viability of HCT 116 cells and induced autophagy. Furthermore, we found that polyphyllin Ι induced autophagy in an ROS-dependent cell death and not related with PI3 K/AKT/mTOR pathway. We also provide evidence that excessive ROS triggered by polyphyllin Ι could induce G2/M phase arrest via regulating cycle proteins expression of cell cycle regulators, such as p21 and cyclinB1. In conclusion, polyphyllin Ι exhibit anticancer effect through ROS-dependent autophagy and induces G2/M arrest in colorectal cancer.
Phytochemical investigation of the ethanol extract from the rhizomes of Paris polyphylla var. yunnanensis led to the isolation of three steroid saponins (1–3) and two triterpenoid saponins (4, 5). Among them, compound 1 is a new steroid saponin, and 3–5 were obtained for the first time from the genus Paris. Their structures were elucidated on the basis of extensive analyses of spectroscopic data including IR, UV, MS, and 1D and 2D NMR. All of these compounds were tested for their cytotoxic activities on human nasopharyngeal cancer cells (CNE) and antiviral activities against respiratory syncytial virus (RSV). Steroidal saponins 1 and 2 showed moderate effects on CNE cells, with IC50 values 32.56 and 33.10 μM, respectively.
Paris saponins possess anticancer, anti-inflammatory, and antiviral effects. However, the anticancer effect of Paris saponins has not been well elucidated and the mechanisms underlying the potential function of Paris saponins in cancer therapy are needed to be further identify. In this study, we report that saponin compounds isolated from Paris polyphylla exhibited antitumor activity against breast cancer cell lines, MCF-7 and MDA-MB-231. Paris saponin XA-2 induced apoptosis in both cell lines, as evidenced by the activation of caspases and cleavage of Poly (ADP-ribose) polymerase. The ability of XA-2 to induce autophagy was confirmed by acridine orange staining, accumulation of autophagosome-bound Long chain 3 (LC3)-II, and measurement of autophagic flux. XA-2-induced autophagy was observed to promote apoptosis by the combined treatment of breast cancer cell lines with XA-2 and autophagy inhibitors 3-methyladenine and bafilomycin A1, respectively. Moreover, we report a decrease in the levels of Akt/mTOR signaling pathway proteins, such as the phosphorylated forms of Akt, mTOR, P70S6K, and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). Taken together, these results provide important insights explaining the anticancer activity of Paris saponins and the potential development of XA-2 as a new therapeutic agent.
Eleven compounds were isolated from the rhizomes of Paris polyphylla Smith var. yunnanensis. Their structures were elucidated on the basis of rigorous 1D and 2D NMR experiments as well as comparison with the literature data. To the best of our knowledge, compound 1 was only predicted by UPLC/Q-TOF MSE and the NMR spectroscopic data was given for the first time. The cytotoxic activities of all compounds on mouse B16 cells were evaluated. Among the tested molecules, compounds 6–9 showed strong cytotoxicities, while compound 1 did not show significant effect.
Objective:
To study the chemical constituents of aerial parts of Paris polyphylla var. chinensis .
Methods:
Aerial parts of Paris polyphylla var. chinensis was extracted with 95% EtOH, and separated and purified by silica gel, RP 18 and Sephadex LH-20 col- umn chromatography. The structures were identified by spectroscopic analysis.
Results:
A total of ten compounds were isolated and iden- tified as β-sitosterol (1) ergosta-7, 22-dien-3-one (2), β-ecdysone (3), kaempferol (4), daucosterol (5) luteolin (6) calonysterone (7), luteolin-7-O-glucoside (8), quercetin (9), and 3β, 5α, 9α-trihydroxyergosta-7, 22-dien-6-one (10).
Conclusion:
Compounds 2,6 and 10 are isolated from Paris polyphylla var. chinensis for the first time.
Aim: To investigate the chemical constituents of Paris polyphylla Smith var. yunnanensis. Method: Compounds were isolated by silica gel, Sephadex LH-20 and RP-C18 column chromatography and the structures were elucidated on the basis of spectroscopic methods. Result: Nine compounds were isolated and identified as steroidal saponins: (23S, 25S)-3β, 23, 27-trihydroxyspirost- 5-en-3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (1), paris saponin I (2), paris saponin II (3), (25R) diosgenin-3-O-β-D-glucopyranoside(4), (25R) diosgenin-3-O-α-L-arabinofuranosyl(1→4)-β-D- glucopyranoside (5), (25R) diosgenin-3-O-α- L-rhamnopyranosyl(1→2)-β-D-glucopyranoside(6), (25R) diosgenin-3-O-α-L-glucopyranosyl(1→3) [α-L-rhamnopyranosyl(1→2)]-β-D-glucopyranoside(7), (25R) pennogenin-3-O-α-L-arabinofuranosyl(1→4) [α-L-rhamnopyranosyl(1→2)-β-D-glucopyranoside (8) and (25R) pennogenin-3-O-α-L-rhamnopyranosyl(1→4)-α-L- rhamnopyranosyl(1→4)-[α-L-rhamnopyranosyl (1→2)]-β-D- glucopyranoside(9). Conclusion: Compound 1 is a novel steroidal saponin.
Polyphyllin VI (PVI) and polyphyllin VII (PVII) derived from Paris polyphylla possess anti-cancer activities. However, the mechanisms for the anti-lung cancer effects of PVI and PVII remain poorly understood. In this study, PVI and PVII exhibited inhibitory effects on the proliferation of A549 and NCI-H1299 cells. PVI and PVII induced G2/M cell cycle arrest and triggered apoptosis. PVI and PVII upregulated the tumor suppressor protein p53 and downregulated cyclin B1. The two treatments significantly increased the expression levels of death receptor 3, death receptor 5, Fas, cleaved PARP, and cleaved caspase-3. Furthermore, PVI and PVII significantly inhibited the growth of A549 cells in vivo. The tumor inhibitory rates of PVI were 25.74%, 34.62%, and 40.43% at 2, 3, and 4 mg/kg, respectively, and those of PVII were 25.63%, 41.71%, and 40.41% at 1, 2, and 3 mg/kg, respectively. Finally, PVI and PVII regulated the expression of proteins related to the apoptotic pathway in A549 xenografts. In summary, PVI and PVII exhibited strong inhibitory effects on lung cancer cell growth in vitro and in vivo by inducing G2/M cell cycle arrest and triggering apoptosis. Copyright © 2015 John Wiley & Sons, Ltd.
Copyright © 2015 John Wiley & Sons, Ltd.
Two previously unreported spirostanol saponins, dianchonglouosides A and B (1 and 2), along with 7 known steroidal saponins (3–9) were isolated from the rhizomes of Paris polyphylla var. yunnanensis. Their structures were elucidated by extensive spectroscopic analysis (MS, 1D, and 2D NMR), and chemical methods. The cytotoxic activities of the isolated compounds 1–9 were also evaluated against two human cancer cell lines (HEK293 and HepG2). The results showed that compound 7 had the strongest cytotoxic activity against the two cancer cell lines with the IC50 values of 0.6 and 0.9 μM, respectively.
Previously, four steroid glycosides (Pa-d) were isolated from the rhizomes of Paris polyphylla SM. and characterized. In a continuation of our studies on this plant, a further five new steroid glycosides (1, 2, 12, 14 and 16) together with three known compounds (13, 18 and 19 ; the latter two have been obtained synthetically as acetyl derivatives) have been isolated and their structures established as follows. 1 and 2 : (22ξ, 25R)-22-methoxyfurostanol 3, 26-O-bisglycosides (proto-type saponins) corresponding to Pa [diosgein 3-O-α-L-ara·fur-(1→4)-[α-L-rha·pyr-(1→2)]-β-D-glc·pyranoside (3)] and Pb [diosgein 3-O-α-L-rha·pyr-(1→4)-α-L-rha·pyr-(1→4)-[α-L-rha·pyr-(1→2)]-β-D-glc·pyranoside (6)], respectively ; 12 and 13 : pennogenin oligosides having the same sugar moieties as 3 and 6, respectively ; 14 and 18 : pennogenin derivatives carrying 3-O-α-L-ara·fur-(1→4)-β-D-glc·pyranoside and hexaacetyl 3-O-α-L-rha·pyr-(1→2)-β-D-glc·pyranoside, respectively ; 16 and 19 : diosgenin derivatives carrying the same sugar moieties as 14 and 18, respectively.
Steroidal saponins are the major bioactive constituents in Paris Polyphylla. In the present study, we developed a novel analysis method for separation and characterization of steroidal saponins in Paris Polyphylla extract using high-performance liquid chromatography electrospray ionization time of flight mass spectrometry (HPLC/ESITOFMS) and ion trap mass spectrometry (HPLC/ITMS). A total of 30 steroidal saponins in Paris Polyphylla extract were identified effectively according to their accurate mass measurements, molecular formulae, and various characteristic fragmentation behaviors. It is concluded that the established analysis method is sensitive, rapid, and practical. Additionally, it will provide help for further quality control and pharmacological mechanism study of Paris Polyphylla.
Based on a single-factor test, a central composite design was used to optimize the extraction conditions of polysaccharides from leaves of Paris polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz. Three independent variables, including extraction temperature (°C), ratio of water to raw material, and extraction time (h), which significantly affected the yield of polysaccharides, were investigated. The experimental data were fitted to a quadratic polynomial equation using multiple regression analysis and also examined using appropriate statistical methods. The optimum conditions were as follows: extraction temperature, 90.8 °C; ratio of water to raw material, 21.3:1; and extraction time 4.8 h. Under these conditions, the experimental yield was 54.18%, which matched the predicted value well. Furthermore, the purified polysaccharide exerted strong antioxidant effects on DPPH, hydroxyl, and superoxide radicals in vitro.
Paristerone, a novel phytoecdysone has been isolated from the tubers of P. polyphylla and its structure and stereochemistry has been established as 2α, 3β, 14α, 20(R), 22(r), 25-hexahydroxy-5β-chloest-7-en-6-one (2-epiecdysterone) on the basis of chemical and physical evidence.
From Paris polyphylla var. chinensis Hare (Liliaceae), four diosgenin glycosides with haemostatic effects were isolated. The structure of the major component was elucidated by chemical and spectroscopic methods as 3-{[α-L-rhamnopyranosyl(1Rha → 2Glu)]-[α-L-arabinofuranosyl(1Ara → 4Glu)]-β D-glucopyranosyl}-25(R)-spirost-5-en-3β-ol. This saponin was found to be identical to three previously reported compounds to which other structures were originally assigned, namely the major component from P. polyphylla Smith, the major cytotoxic component of yunnan paiyao, and polyphyllin D from P. polyphylla grown in the Himalaya region.
A novel steroidal saponin, along with 12 known steroidal compounds, was isolated from the rhizomes of Paris polyphylla var. chinensis. Spectral data, including two-dimensional NMR, showed that the structure of the novel saponin was 3β,21-dihydroxypregnane-5-en-20S-(22,16)-lactone-1-O-α-L-rhamnopyranosyl(1→2)-[β-D-xylopyranosyl(1→3)]-β-D-glucopyranoside. The isolated steroidal compounds were evaluated for their cytotoxic activity on human gastric cancer cell
line HepG2, SGC7901, BxPC3. Diosgenin-3-O-α-L-rhamnopyranosyl(1→2)[α-L-rabinofuranosyl(1→4)]-β-D-glucopyranoside exhibited the most potent cytotoxic activity among the isolated steroids.
Two new homo-aro-cholestane glycosides and a new cholestane glycoside, along with three known saponins, were isolated from the 95% EtOH extract of the roots and rhizomes of Paris polyphylla var. pseudothibetica. The structures of the new compounds were elucidated as 3β-O-{α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]}-β-D-glucopyranosylhomo-aro-cholest-5-ene-26-O-β-D-glucopyranoside (parispseudoside A, 1), 3β-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosylhomo-aro-cholest-5-ene-26-O-β-D-glucopyranoside (parispseudoside B, 2), and (25R)-3β-O-{α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]}-β-D-glucopyranosyl-cholesta-5,17(20)-diene-16,22-dione-26-O-β-D-glucopyranoside (parispseudoside C, 3) by spectroscopic methods, including 1D- and 2D-NMR, and MS experiments, as well as chemical evidences.
The structure of two new saponins, polyphyllins G and H, isolated from the tubers of Paris polyphylla have been elucidated as 3-O-{α-l-rhamnopyranosyl (1→3) [α-l-arabinofuranosyl (1→4)]-β-d-glucopyranosyl}-26-O-[β-d-glucopyranosyl] (25R)-22α-hydroxy-furost-5-en-3β, 26-diol and its 22-methoxy derivative respectively.
The study reveals that the people of the Uttaranchal state use 364 plants species in ethnoveterinary practices. Bhotiyas, Boxas, Tharus, Jaunsaris and Rhajis are the tribal groups inhabiting in Uttaranchal. Analysis of data indicates that information on 163 plants is significant as it provides some new information of the ethnoveterinary uses. The study is expected to provide basic data for further studies aimed at conservation of traditional medicine and economic welfare of rural people at the study area.
Phytochemical investigation of the rhizomes of Paris polyphylla var. yunnanensis resulted in the isolation of six new oleanane-type triterpenoid saponins, paritrisides A-F (1-6), along with nine known triterpenoid saponins (7-15). The structures of the new compounds were elucidated on the basis of spectroscopic analysis and acid hydrolysis. All the triterpenoid saponins are obtained for the first time from the genus Paris. The isolated compounds were assayed for their cytotoxic activities against human nasopharyngeal carcinoma epithelial (CNE) cells, and compounds 7, 8, and 10 exhibited inhibitory effects on CNE cell growth with IC(50) values of 16.53, 16.77, and 12.69μm, respectively.
A new spirostanol steroidal saponin, along with ten known saponins, which were based upon (25R)-spirost-5-en-3β-o1 (diosgenin) or (25R)-spirost-5-ene-3β5,17α-diol (pennogenin) as the aglycones, were isolated from the rhizomes of Paris polyphylla var. chinensis. Spectral data, including two-dimensional NMR, and the result of hydrolytic cleavage showed that the structure of the new saponin was pennogenin 3-0-{O−α-L-rhamnopyranosyl-(1→4)-O a-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside}. The isolated saponins were evaluated for their cytotoxic activity on human promyelocytic leukemia HL-60 cells.
Rhizoma Paridis saponins (RPS) have been well studied for antimicrobial, anti-hemorrhagic, and anticancer effects. However, scientific information on RPS regarding the toxic and neuropharmacological effects is limited. In this study, the acute oral toxicity, sedative-hypnotic activity and gastro-intestinal toxicity of RPS were investigated.
The acute toxicity was carried out by administering single doses (800-5000mg/kg) of RPS to adult mice. Rotarod test and sodium pentobarbital-induced hypnosis activity were used to evaluate the neuropharmacological effects on mice. Gastric emptying and intestinal transit were used to investigate the gastric-intestinal system effects.
A single oral administration of RPS dose-dependently caused adverse effects on the general behavior and mortality rate of mice. LD(50) value of oral acute toxicity was 2182.4mg/kg, with 95% confidence limit of 1718.4-2807.8mg/kg. In the test of sleeping mice, RPS acted in synergy with sodium pentobarbital at doses 250 and 500mg/kg while motor coordination was not influenced within 120min after treatment with RPS. Regarding the gastric-intestinal toxicity, RPS (100, 250, and 500mg/kg) significantly inhibited gastric emptying but did not affect the intestinal transit.
RPS, which is a hypotoxic anticancer drug, possesses the sedative-hypnotic activity and gastric stimulus side effect.
Four new steroidal saponins, pariposides A-D (1-4), and two new sterol glycosides, pariposides E-F (5-6), along with eight known steroidal saponins (7-14), two known sterol glycosides (15-16), and two known ecdysteroids (17-18), were isolated from the roots of Paris polyphylla var. yunnanensis. Among them, compounds 1-4 are the first spirostanol saponins with a peroxy group located between C-5 and C-8 of the aglycone. Their structures were determined by detailed spectroscopic analyses and chemical methods. All the isolated compounds were evaluated for their in vitro cytotoxicities against human nasopharyngeal carcinoma epithelial (CNE) cells, and steroidal saponins 7, 11, 13, and 14 showed a potent antiproliferative effect on CNE cells with IC50 values of 9.2, 4.7, 11.1, and 2.7 µM, respectively.