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1

Navrátilová, Zdeňka. "Gynostemma pentaphyllum - active compounds and therapeutic effects." Praktické lékárenství 13, no. 3 (October 1, 2017): 116–18. http://dx.doi.org/10.36290/lek.2017.015.

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2

Liang, Renji, Jinzheng Wu, Ronghua Lin, Liling Ran, Bo Shu, and Hao Deng. "Molecular Mechanisms of Gynostemma pentaphyllum in Prevention and Treatment of Non-Small-Cell Lung Cancer." Evidence-Based Complementary and Alternative Medicine 2022 (September 6, 2022): 1–8. http://dx.doi.org/10.1155/2022/9938936.

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Objective. Lung cancer represents the leading cause of cancer death on a global scale. Gynostemma pentaphyllum (G. pentaphyllum), a traditional medicinal material with a high medicinal and health value, has recently been reported for its anticancer activity. However, the pharmacological mechanism of G. pentaphyllum in non-small-cell lung cancer (NSCLC) remains to be elucidated. Methods. The active ingredients of G. pentaphyllum were obtained from the TCMSP database and known therapeutic targets of NSCLC from the GeneCards and OMIM databases. Disease-drug common targets are subjected to protein-protein interaction (PPI), GO enrichment analysis, and KEGG pathway enrichment analysis. A molecular docking strategy was performed to verify the interaction between molecules. Results. We found a total of 24 compounds of G. pentaphyllum fulfilling OB ≥ 30% concomitant with DL ≥ 0.18 and corresponding 81 target genes in the TCMSP database, with 5062 NSCLC-related genes collected in the GeneCards and OMIM databases. The network consisting of the disease-target compound was obtained, including 8 active ingredients and 69 common targets. The PPI network with 65 nodes and 645 edges was visualized. After functional enrichment analysis, it was revealed that the therapeutic effects of G. pentaphyllum on NSCLC were achieved through response to ketone, gland development, and cellular response to xenobiotic stimulus. After molecular docking analysis, it was revealed that the two active ingredients of G. pentaphyllum, quercetin and rhamnazin, bound well and stably to their targets (MYC, ESR1, and HIF1A). Conclusion. Our study, based on network pharmacology, identifies active ingredients, targets, and pathways model mechanism of G. pentaphyllum when it is used to treat NSCLC.
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Kim, Min Young. "Cytotoxicity and acute toxicity evaluation of hydrogen-rich Gynostemma pentaphyllum Makino distillate." Journal of Applied and Natural Science 14, no. 3 (September 16, 2022): 771–76. http://dx.doi.org/10.31018/jans.v14i3.3569.

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Hydrogen-rich Gynostemma pentaphyllum Makino distillate (HRGD) consists of Gynostemma pentaphyllum Makino steam distillate with hydrogen gas. Although both G. pentaphyllum Makino and hydrogen-rich water are well known for their biological and medical benefits, there is a lack of information on their safety and toxicity in vivo acute oral toxicity test and in vitro cytotoxicity method. The current study aimed to assess the cytotoxicity and acute oral toxicity of HRGD as a part of a safety evaluation using rat and human cell models. HRGD was administered orally once by gavage to male and female Sprague-Dawley rats at doses of 0, 2500, and 5000 mg/kg. Cytotoxicity assay was conducted in vitro at various concentrations in 10 different human normal and cancer cell lines; TK6 (human normal lymphomablastoid cells), Chang (human hepatic cells), 16HBE14o- (human bronchial epithelial cells), URotsa (human urothelium cells), MCF (human breast cancer cells), Hela (human cervical cancer cells), A375 (human malignant melanoma cells), HCT116 (human colon cancer cells), HepG2 (human liver cancer cells) and A549 (human non-small cell lung adenocarcinoma cells). From a 14-day study in rats, we observed no compound-related changes in mortality, clinical signs, body weight, food/water consumption, organ weight and gross pathology in all dose group. The result of in vivo acute toxicity shows that no observed adverse effect level of HRGD was below 5000 mg/kg for both sexes of rats, and the minimal lethal dose was considered to be more than 5000 mg/kg. HRGD also had no in vitro cytotoxicity against all tested cells. The present study data indicated that HRGD may contain bioactive compounds of potential therapeutic significance that are relatively safe from toxic effects.
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Li, Xiao-Li, Zheng-Hui Wang, Yong-Xi Zhao, Su-Ju Luo, Ding-Wei Zhang, Sheng-Xiang Xiao, and Zhen-Hui Peng. "Purification of a polysaccharide from Gynostemma pentaphyllum Makino and its therapeutic advantages for psoriasis." Carbohydrate Polymers 89, no. 4 (August 2012): 1232–37. http://dx.doi.org/10.1016/j.carbpol.2012.04.001.

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Chen, Jung-Chou, Chin-Chuan Tsai, Leih-Der Chen, Hing-Ho Chen, and Wen-Chuang Wang. "Therapeutic Effect of Gypenoside on Chronic Liver Injury and Fibrosis Induced by CCl4 in Rats." American Journal of Chinese Medicine 28, no. 02 (January 2000): 175–85. http://dx.doi.org/10.1142/s0192415x00000222.

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Gypenoside is a saponins extract derived from the Gynostemma pentaphyllum. The purpose of this study was to evaluate the hepatoprotective and antifibrotic potential of Gypenoside on chronic liver injury induced by CCl 4 for 8 wks. The results indicated that the increase of SGOT, SGPT activities in CCl 4 liver injury were significantly reduced by treatment with Gypenoside. It also elevated the A/G ratio. For the study of anti-fibrotic potential, Gypenoside reduced the collagen content by 33%. These phenomena were confirmed by pathologic observation; thinner bands of liver collagen were found. The results suggest that Gypenoside has hepatoprotective and anti-fibrotic activities.
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Zhong, Jiao, and Lu Wang. "Gypenoside XVII Inhibits High Glucose-Induced Apoptosis and Facilitates Osteogenic Differentiation in MC3T3-E1 Cells." Current Topics in Nutraceutical Research 20, no. 1 (February 26, 2021): 129–34. http://dx.doi.org/10.37290/ctnr2641-452x.20:129-134.

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Osteoporosis is a systemic bone disease characterized by compromised bone strength, which predisposes the individual to an increased risk of fractures of the hip, spine, and other skeletal sites. Gynostemma pentaphyllum (of the family Cucurbitaceae) is known to reduce blood lipid, prevent arteriosclerosis, inhibit oxidation, reduce blood glucose, and regulate immunity. Gypenoside XVII is one of the bioactives in G. pentaphyllum, which inhibits receptor activator of nuclear factor-kappa B ligand-induced osteoclast production. Herein, we show that Gypenoside XVII improves the survival of MC3T3-E1 under high glucose environment. It also inhibits the apoptosis of MC3T3-E1 cells in high glucose environment. In addition, Gypenoside XVII promotes osteogenic differentiation of MC3T3-E1 cells in high glucose environment. Mechanically, we found that Gypenoside XVII inhibited high glucose-induced apoptosis and facilitated osteogenic differentiation via activating the PI3K/AKT pathway. These data suggest that Gypenoside XVII might be a potential therapeutic drug in the treatment of osteoporosis.
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7

Wang, Miao, Fei Wang, Yinan Wang, Xiaonan Ma, Min Zhao, and Chunjie Zhao. "Metabonomics Study of the Therapeutic Mechanism of Gynostemma pentaphyllum and Atorvastatin for Hyperlipidemia in Rats." PLoS ONE 8, no. 11 (November 1, 2013): e78731. http://dx.doi.org/10.1371/journal.pone.0078731.

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8

Li, Kaijun, Chao Ma, Haoyu Li, Sooranna Dev, JianFeng He, and Xiaosheng Qu. "Medicinal Value and Potential Therapeutic Mechanisms of Gynostemma pentaphyllum (Thunb.) Makino and Its Derivatives: An Overview." Current Topics in Medicinal Chemistry 19, no. 31 (January 3, 2020): 2855–67. http://dx.doi.org/10.2174/1568026619666191114104718.

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: Gynostemma pentaphyllum (Thunb.) Makino (GpM) and its derivatives, especially gypenosides (Gyps), are widely used as safe and convenient natural herbal drugs for the treatment of many diseases for a long time, and Gyps have different oral bioavailability (OB) values and low ability to cross the blood-brain barrier (BBB). The effects of GpM and isolates on fibrosis, inflammation, oxidation, proliferation and migration are proved. GpM shows bidirectional regulation effect on proliferation, oxidation and apoptosis in tumor and non-tumor cells. GpM and its extractions can resist proliferation, activate oxidation and apoptosis in tumor cells and have opposite effects on non-tumor cells. We succinctly present some current views of medicinal value and potential therapeutic mechanisms of GpM and its derivatives.
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9

Xing, Shao-Fang, Lin-Hua Liu, Ma-Li Zu, Man Lin, Xin-Fang Zhai, and Xiang-Lan Piao. "Inhibitory Effect of Damulin B from Gynostemma pentaphyllum on Human Lung Cancer Cells." Planta Medica 85, no. 05 (December 18, 2018): 394–405. http://dx.doi.org/10.1055/a-0810-7738.

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AbstractDamulin B, a dammarane-type saponin from steamed Gynostemma pentaphyllum, exhibits the strongest activity against human lung carcinoma A549 cells among the isolated active saponins. In this study, the structure-activity relationship of a series of saponin compounds was discussed. The inhibitory effect of damulin B on human lung cancer A549 and H1299 cells was investigated from apoptosis, cell cycle, and migration aspects. In vitro, human lung cancer cells were more susceptible to damulin B treatment than human normal fibroblasts. Damulin B exhibited a strong cytotoxic effect, as evidenced by the increase of apoptosis rate, reduction of mitochondrial membrane potential (MMP), generation of reactive oxygen species, and G0/G1 phase arrest. Furthermore, damulin B activated the following: both intrinsic and extrinsic apoptosis pathways along with early G1 phase arrest via the upregulation of the Bax, Bid, tBid, cleaved caspase-8, and p53 expression levels; downregulation of the procaspase-8/-9, CDK4, CDK6, and cyclin D1 expression levels; and more release of cytochrome c in the cytoplasm. In addition, antimigratory activities and suppressive effects on metastasis-related factors, such as MMP-2 and MMP-9, accompanied by the upregulation of IL-24 were revealed. Altogether, the results proved that damulin B could inhibit human lung cancer cells by inducing apoptosis, blocking the cell cycle at early G0/G1 phase and suppressing the migration. Hence, damulin B has potential therapeutic efficacy against lung cancer.
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10

Mastinu, Andrea, Sara Anna Bonini, Marika Premoli, Giuseppina Maccarinelli, Eileen Mac Sweeney, Leilei Zhang, Luigi Lucini, and Maurizio Memo. "Protective Effects of Gynostemma pentaphyllum (var. Ginpent) against Lipopolysaccharide-Induced Inflammation and Motor Alteration in Mice." Molecules 26, no. 3 (January 22, 2021): 570. http://dx.doi.org/10.3390/molecules26030570.

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Gynostemma pentaphyllum (var. Ginpent) (GP) is a variety of Cucurbit with anti-inflammatory and antioxidant effects in patients. In this manuscript, the main components present in the dry extract of GP have been identified using Ultra High Performance Liquid Chromatography quadrupole-time-of-flight mass spectrometry (UHPLC/Q-TOF-MS). In addition, the anti-inflammatory action of GP was evaluated in animal models with acute peripheral inflammation and motor alteration induced by lipopolysaccharide. The results showed that GP dry extract is rich in secondary metabolites with potential antioxidant and anti-inflammatory properties. We found that the treatment with GP induced a recovery of motor function measured with the rotarod test and pole test, and a reduction in inflammatory cytokines such as interleukin-1β and interleukin-6 measured with the ELISA test. The data collected in this study on the effects of GP in in vivo models may help integrate the therapeutic strategies of inflammatory-based disorders.
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11

Yu, Fan. "Preparation, Characteristics and Bioactivity of Gypenosides-Loaded Microcapsules." Advanced Materials Research 710 (June 2013): 195–98. http://dx.doi.org/10.4028/www.scientific.net/amr.710.195.

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Microencapsulation has great potential extensive applications in fields of cosmetics, pesticides, pharmaceutical and medical applications, foods, biology, catalysis, carbonless copying paper and many other areas. Gypenosides (GPS) are extracted from Gynostemma pentaphyllum Makino, widely used in Southeast Asian folk medicine or food. In the current study, Gypenosides-loaded microcapsules (GPMC) were prepared by gelatin/gum. Characteristics and bioactivity of the GPMC were evaluated. An up to 80% encapsulation of GPS at pH 4.0 was achieved, with 1:2 drug to wall materials ratio and a 3% gelatin/gum arabic while stirring at 500 r/min. Microscopy revealed an average microcapsule size of 52.4 μm. Pharmacological studies showed that GPMC exhibited excellent therapeutic effects, such as expectorant activity, cough relieving and anti-inflammatory effect. The results indicate that microcapsulation is a safe and efficient delivery for GPS.
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12

Li, Xiuming, Hui Liu, Chengcheng Lv, Jun Du, Fangchao Lian, Shouyi Zhang, Zhiyong Wang, and Yu Zeng. "Gypenoside-Induced Apoptosis via the PI3K/AKT/mTOR Signaling Pathway in Bladder Cancer." BioMed Research International 2022 (March 29, 2022): 1–15. http://dx.doi.org/10.1155/2022/9304552.

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Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is a natural herbal drug that has been widely used to treat many diseases. The antitumor effects of G. pentaphyllum were first described in the illustrated catalog of plants. Gypenosides are the major active components of G. pentaphyllum, and they have been widely reported to possess antitumor effects in prostate cancer, gastric cancer, hepatocellular carcinoma, colon cancer, lung cancer, and breast cancer. However, research on the use of gypenoside in the treatment of bladder cancer has not been conducted. In this study, we explored the potential molecular mechanisms of gypenosides in the treatment of bladder cancer using network pharmacology and experimental validation. First, we used a network pharmacology–based method to identify both the effective components of gypenosides and the molecular mechanism underlying their antibladder cancer effects. The results were further confirmed by molecular docking, CCK8 and colony formation assays, and cell cycle and cell apoptosis analyses. Additionally, a mouse xenograft model of bladder cancer was used to investigate the antitumor effect of gypenosides in vivo. We identified 10 bioactive ingredients and 163 gene targets of gypenosides. Network exploration suggested that VEGFA, STAT3, and PI3KCA may be candidate agents for the antibladder cancer effect of gypenosides. In addition, analysis of the Kyoto Encyclopedia of Genes and Genomes pathway revealed that the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway may play a crucial role in the mechanism of action of gypenosides against bladder cancer. Molecular docking revealed that gypenosides combine well with PI3K, AKT, and mTOR. As expected, gypenosides displayed apoptosis-inducing properties in bladder cancer cells by inactivating the PI3K/AKT/mTOR signaling pathway in vitro. Furthermore, gypenosides significantly ( P < 0.05 ) inhibited the growth of bladder cancer cells in vivo. Mechanistically, gypenosides induced the apoptosis of bladder cancer cells via inactivation of the PI3K/AKT/mTOR signaling pathway.
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Bae, Ui-Jin, Eun-Ock Park, John Park, Su-Jin Jung, Hyeonmi Ham, Kee-Won Yu, Young-Jun Park, Soo-Wan Chae, and Byung-Hyun Park. "Gypenoside UL4-RichGynostemma pentaphyllumExtract Exerts a Hepatoprotective Effect on Diet-Induced Nonalcoholic Fatty Liver Disease." American Journal of Chinese Medicine 46, no. 06 (January 2018): 1315–32. http://dx.doi.org/10.1142/s0192415x18500696.

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Nonalcoholic steatohepatitis (NASH) arises from nonalcoholic fatty liver disease (NAFLD) as a consequence of oxidative stress. Gynostemma pentaphyllum extract (GPE) is proven to be beneficial for patients suffering from NAFLD. However, the precise mechanism by which GPE confers these benefits remains largely unknown. The purpose of this study was to investigate the underlying mechanism and to determine whether supplementation with the newly discovered GPE gypenoside UL4 mitigates NASH progression. Male c57BL/6 mice were fed a normal chow diet, a methionine choline-deficient (MCD) diet, or an MCD diet supplemented with various doses of UL4-rich GPE for eight weeks. GPE supplementation suppressed oxidative stress induced by the MCD diet by increasing levels of sirtuin 6 and phase 2 anti-oxidant enzymes in mouse liver and HepG2 cells. Additionally, GPE supplementation prevented diet-induced hepatic fat accumulation, hepatocellular injury, inflammation, and fibrosis in mice fed the MCD diet. These results indicate the possible therapeutic potential of dietary supplementation of UL4-rich GPE in preventing the development of fatty liver and its progression to NASH.
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Ma, Jingxin, Xiaopeng Hu, Chenghui Liao, Haitao Xiao, Qinchang Zhu, Ying Li, Zhigang Liu, et al. "Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence." Molecules 24, no. 6 (March 18, 2019): 1054. http://dx.doi.org/10.3390/molecules24061054.

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Senescence is an irreversible state of cell cycle arrest that can be triggered by multiple stimuli, such as oxygen reactive species and DNA damage. Growing evidence has proven that senescence is a tumor-suppressive approach in cancer treatment. Therefore, developing novel agents that modulate senescence may be an alternative strategy against cancer. In our study, we investigated the inhibitory effect of gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, on cancer cell growth. We found that Gyp-L increased the SA-β-galactosidase activity, promoted the production of senescence-associated secretory cytokines, and inhibited cell proliferation of human liver and esophageal cancer cells. Moreover, Gyp-L caused cell cycle arrest at S phase, and activated senescence-related cell cycle inhibitor proteins (p21 and p27) and their upstream regulators. In addition, Gyp-L activated p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Consistently, adding chemical inhibitors efficiently counteracted the Gyp-L-mediated senescence, growth inhibition, and cell cycle arrest in cancer cells. Furthermore, treatment with Gyp-L, enhanced the cytotoxicity of clinic therapeutic drugs, including 5-fluorouracil and cisplatin, on cancer cells. Overall, these results indicate that Gyp-L inhibits proliferation of cancer cells by inducing senescence and renders cancer cells more sensitive to chemotherapy.
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Yang, Guanghui, Jialu Zhang, Shenghua Wang, Jun Wang, Jing Wang, Yaohong Zhu, and Jiufeng Wang. "Gypenoside Inhibits Bovine Viral Diarrhea Virus Replication by Interfering with Viral Attachment and Internalization and Activating Apoptosis of Infected Cells." Viruses 13, no. 9 (September 12, 2021): 1810. http://dx.doi.org/10.3390/v13091810.

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Bovine viral diarrhea virus (BVDV) causes a severe threat to the cattle industry due to ineffective control measures. Gypenoside is the primary component of Gynostemma pentaphyllum, which has potential medicinal value and has been widely applied as a food additive and herbal supplement. However, little is known about the antiviral effects of gypenoside. The present study aimed to explore the antiviral activities of gypenoside against BVDV infection. The inhibitory activity of gypenoside against BVDV was assessed by using virus titration and performing Western blotting, quantitative reverse transcription PCR (RT-qPCR), and immunofluorescence assays in MDBK cells. We found that gypenoside exhibited high anti-BVDV activity by interfering with the viral attachment to and internalization in cells. The study showed that BVDV infection inhibits apoptosis of infected cells from escaping the innate defense of host cells. Our data further demonstrated that gypenoside inhibited BVDV infection by electively activating the apoptosis of BVDV-infected cells for execution, as evidenced by the regulation of the expression of the apoptosis-related protein, promotion of caspase-3 activation, and display of positive TUNEL staining; no toxicity was observed in non-infected cells. Collectively, the data identified that gypenoside exerts an anti-BVDV-infection role by inhibiting viral attachment and internalization and selectively purging virally infected cells. Therefore, our study will contribute to the development of a novel prophylactic and therapeutic strategy against BVDV infection.
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Tan, Yi, Mohammad A. Kamal, Zheng-Zhong Wang, Wei Xiao, John P. Seale, and Xianqin Qu. "Chinese herbal extracts (SK0506) as a potential candidate for the therapy of the metabolic syndrome." Clinical Science 120, no. 7 (December 13, 2010): 297–305. http://dx.doi.org/10.1042/cs20100441.

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The metabolic syndrome has reached epidemic proportions worldwide, but currently there is a lack of effective therapies for this multifactorial endocrine disease. TCM (traditional Chinese medicine) has been utilized to treat a wide variety of diseases for centuries in the People's Republic of China, subsequently becoming a promising source for the development of new therapeutic agents. Chinese medicinal herbs Gynostemma pentaphyllum, Coptis chinensis and Salvia miltiorrhiza have been shown to have anti-atherosclerotic and antidiabetic properties. In this study, we have investigated the metabolic effects of a mixture of these three herbal extracts (SK0506) in a rodent model of the metabolic syndrome induced by an HFD (high-fat diet). SD (Sprague–Dawley) rats that were fed on an HFD for 4 weeks gained 33% more weight compared with chow-fed rats (P<0.05). Four weeks treatment with SK0506 prevented weight gain with decreased visceral fat (P<0.01 compared with vehicle treatment). SK0506 also significantly reduced plasma triacylglycerols (triglycerides), NEFAs (non-esterified fatty acids) and cholesterol. SK0506 exerted similar effects to RSG (rosiglitazone) on impaired glucose intolerance. SK0506 also significantly enhanced glucose uptake and glycogen synthesis in adipose tissue during hyperinsulinaemic–euglycaemic clamp. Western blotting analysis revealed that SK0506 enhanced GLUT4 (glucose transporter 4) expression in adipose tissue, and RSG markedly up-regulated GLUT4 translocation in skeletal muscle. Overall, the present study has discovered that SK0506 can reverse several components of the metabolic syndrome primarily through acting on hyperlipidaemia and visceral obesity. The results from the present study suggest that it is worthwhile to conduct a randomized clinical trial to confirm the potential that SK0506 may be a new oral agent for treating the metabolic syndrome and preventing Type 2 diabetes.
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Dai, Ning, Fang-fang Zhao, Min Fang, Feng-lan Pu, Ling-yao Kong, and Jian-ping Liu. "Gynostemma pentaphyllum for dyslipidemia: A systematic review of randomized controlled trials." Frontiers in Pharmacology 13 (August 26, 2022). http://dx.doi.org/10.3389/fphar.2022.917521.

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Objective: To evaluate the lipid-lowering effect and safety of Gynostemma pentaphyllum (GP) used alone or as adjunctive therapy for dyslipidemia.Methods: Eight databases and three clinical trial registries were searched until January 2022. Randomized controlled trials (RCTs) assessing the effectiveness of GP for dyslipidemia were included. Trial quality was assessed using the Cochrane Risk of Bias Tool 2.0. Data were analyzed by RevMan 5.4 with effects estimated as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).Results: Twenty-two RCTs involving 2,407 dyslipidemia participants were included. Regarding the risk of bias, 14 RCTs had some concerns, seven RCTs were high, and one trial was low. GP was comparable to n-3 fatty acids (RR 0.89, 95% CI 0.62–1.28) and red yeast rice (RR 0.33, 95% CI 0.1–1.12) on normalization of serum lipids. GP plus n-3 fatty acid was superior in normalization of triglycerides (TG) and total cholesterol (TC) than n-3 fatty acids (RR 1.34, 95% CI 1.01–1.77). GP was similar to lipid-lowering agents (statins, fibrates, and n-3 fatty acids) in regulating TG, TC, and high-density lipoprotein cholesterol (HDL-C). GP plus lipid-lowering agents were superior to lipid-lowering agents in TG (MD −0.65 mmol/L, 95% CI −1.03 to −0.28), LDL-C (MD −0.57 mmol/L, 95% CI −1.07 to −0.08), and HDL-C (MD 0.15 mmol/L, 95% CI 0.11–0.20). GP was inferior to red yeast rice in TC (MD 0.64 mmol/L, 95% CI 0.15–1.13), TG (MD 0.43 mmol/L, 95% CI 0.15–0.71), and HDL-C (MD −0.25 mmol/L, 95% CI −0.47 to −0.04). GP had fewer adverse events than lipid-lowering drugs.Conclusion: Very low certainty evidence showed that GP’s effects on TC, TG, and HDL-C were comparable to that of lipid-lowering agents. Low certainty evidence showed that red yeast rice was superior to GP in TC, TG, and HDL-C. Low to moderate certainty evidence showed that the effects of GP plus lipid-lowering agents were superior to that of lipid-lowering agents on TG, LDL-C, and HDL-C. GP use for more than 8 weeks appears safe.Systematic Review Registration:https://inplasy.com/, identifier INPLASY202210135.
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Wang, Jiahao, Jiamiao Shi, Ning Jia, and Qinru Sun. "Network pharmacology analysis reveals neuroprotection of Gynostemma pentaphyllum (Thunb.) Makino in Alzheimer’ disease." BMC Complementary Medicine and Therapies 22, no. 1 (March 7, 2022). http://dx.doi.org/10.1186/s12906-022-03534-z.

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Abstract Background Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders in the world, but still lack of effective drug treatment. Gynostemma Pentaphyllum (Thunb.) Makino (GpM), a Chinese medicinal herb, plays important roles in anti-inflammation, anti-oxidative stress and anti-tumor, which has been reported to ameliorate cognitive impairment of AD. However, the neuroprotective mechanism of GpM remains unclear. This study aims to investigate the targets and possible signaling pathways of GpM in the treatment of AD. Methods Active compounds of GpM and their putative target proteins were selected from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform. AD-associated targets were identified from GeneCards, the Online Mendelian Inheritance in Man (OMIM) database and the Therapeutic Target Database (TTD). The intersecting targets of GpM and AD were identified and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out to analyze the mechanism of them. Compound-target-pathway (CTP) network and protein–protein interaction (PPI) network were constructed and analyzed to elucidate the correlation between compounds, proteins and pathways. Molecular docking was performed to further demonstrate the possibility of GpM for AD. Results A total of 13 active compounds of GpM, 168 putative target proteins of compounds and 722 AD-associated targets were identified. Eighteen intersecting targets of GpM and AD were found and the epidermal growth factor receptor (EGFR), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), nitric oxide synthase in endothelial (NOS3) and serum paraoxonase/arylesterase 1 (PON1) were selected as the primary targets of GpM in the treatment of AD. The neuroprotective effect of GPM was related to a variety of pathways, including amoebiasis, HIF-1 signaling pathway, cytokine-cytokine receptor interaction and so on. Conclusions Our findings elucidate the active compounds, targets and pathways of GpM involved in effects of anti-AD. The novel mechanism of GpM against AD provides more treatment options for AD.
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Fu, Yadong, Zhun Xiao, Xiaoting Tian, Wei Liu, Zhou Xu, Tao Yang, Yonghong Hu, et al. "The Novel Chinese Medicine JY5 Formula Alleviates Hepatic Fibrosis by Inhibiting the Notch Signaling Pathway." Frontiers in Pharmacology 12 (September 22, 2021). http://dx.doi.org/10.3389/fphar.2021.671152.

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Advanced liver fibrosis can lead to cirrhosis, resulting in an accelerated risk of hepatocellular carcinoma and liver failure. Fuzheng Huayu formula (FZHY) is a traditional Chinese medicine formula treated liver fibrosis in China approved by a Chinese State Food and Drug Administration (NO: Z20050546), composed of Salvia Miltiorrhiza bge., Prunus davidiana (Carr.) Franch., cultured Cordyceps sinensis (BerK.) Sacc. Mycelia, Schisandra chinensis (Turcz.) Baill., Pinus massoniana Lamb., and Gynostemma pentaphyllum (Thunb.) Makino. However, the main active substances and mechanism of FZHY are unclear. The aim of this study is to identify a novel anti-fibrotic compound, which consists of the main active ingredients of FZHY, and investigate its mechanism of pharmacological action. The main active ingredients of FZHY were investigated by quantitative analysis of FZHY extracts and FZHY-treated plasma and liver in rats. The anti-fibrotic composition of the main active ingredients was studied through uniform design in vivo, and its mechanism was evaluated in carbon tetrachloride (CCl4)- and bile duct ligation (BDL)-induced liver fibrosis models in rats and mice, and transforming growth factor beta 1-induced LX-2 cell activation model in vitro. A novel Chinese medicine, namely JY5 formula, consisting of salvianolic acid B, schisantherin A, and amygdalin, the main active ingredients of FZHY, significantly alleviated hepatic hydroxyproline content and collagen deposition in CCl4-and BDL-induced fibrotic liver in rats and mice. In addition, JY5 inhibited the activation of hepatic stellate cells (HSCs) by inactivating Notch signaling in vitro and in vivo. In this study, we found a novel JY5 formula, which exerted anti-hepatic fibrotic effects by inhibiting the Notch signaling pathway, consequently suppressing HSCs activation. These results provide an adequate scientific basis for clinical research and application of the JY5 formula, which may be a potential novel therapeutic candidate for liver fibrosis.
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Cao, Li-Hua, Yuan-Yuan Zhao, Ming Bai, David Geliebter, Jan Geliebter, Raj Tiwari, Hong-Juan He, et al. "Mechanistic Studies of Gypenosides in Microglial State Transition and its Implications in Depression-Like Behaviors: Role of TLR4/MyD88/NF-κB Signaling." Frontiers in Pharmacology 13 (March 15, 2022). http://dx.doi.org/10.3389/fphar.2022.838261.

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Abstract:
Depression is a prevalent psychiatric disorder. Microglial state transition has been found in many neurological disorders including depression. Gypenosides (Gypenosides I-LXXVIII, Gps) are saponin extracts isolated from the traditional Chinese herb Gynostemma pentaphyllum (Thunb.) Makino that exert anti-inflammatory and neuroprotective activities and regulate depression-like behaviors. However, its effect on microglial state transition in depression remains unknown. We aimed to evaluate the potential relationship between Gps and TLR4/MyD88/NF-κB signaling in microglial state transition in vitro and in vivo. First, BV-2 cells (microglial cell line) were exposed to lipopolysaccharides (LPS) and treated with 10 or 5 μg/ml Gps. Second, the chronic unpredictable mild stress (CUMS)-induced depression mouse model was used to investigate the antidepressant-like behaviors effects of Gps (100 or 50 mg/kg). We determined depression-like behaviors using the open-field test (OFT), forced swim test (FST), and sucrose preference test (SPT). Proteins and inflammatory factors in the TLR4/MyD88/NF-κB signaling pathway and the different microglial reaction states markers were subsequently conducted using enzyme-linked immunosorbent assay, immunocytochemistry, immunofluorescence, qPCR, or Western blotting analyses to evaluate the anti-inflammatory and antidepressant properties of Gps and the underlying molecular mechanisms. We found that Gps regulated the microglial cell line state transition in LPS-exposed BV-2 cells, as evidenced by the significantly decreased expression of inflammatory parameters iNOS, IL-1β, IL-6, and TNF-α and significantly promoted anti-inflammatory microglial phenotypes markers CD206 (Mrc1) and IL-10. More importantly, Gps protected against the loss of monoamine neurotransmitters and depression-like behavior in a mouse model of depression, which was accompanied by a regulation of the microglial state transition. Mechanistically, Gps inhibited TLR4/MyD88/NF-κB signaling, which reduced the release of downstream inflammatory cytokines (IL-1β, IL-6, and TNF-α) and promoted microglial phenotype transition, which all together contributed to the antidepressant effect. Our results suggest that Gps prevents depression-like behaviors by regulating the microglial state transition and inhibiting the TLR4/MyD88/NF-κB signaling pathway. Thus, Gps could be a promising therapeutic strategy to prevent and treat depression-like behaviors and other psychiatric disorders.
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