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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.

Objectives Hair graying, often linked to aging (oxidative stress), has gained significant attention due to its social implications and the desire for a youthful appearance. Currently, there is no effective solution. The objective of this study was to determine whether Gynostemma pentaphyllum (Thunb.) Makino extract (GP) can mitigate the effects of H2O2‐induced oxidative stress in melanocytes and evaluate its potential as a treatment for hair graying. Methods Oxidative stress models were established using B16 melanoma cells and C57BL/6 mice. GP treatment’s effects on cell viability, melanocyte apoptosis, intracellular reactive oxygen species (ROS) levels, melanin production, tyrosinase activity, total superoxide dismutase (SOD) activity, and the Wnt/β‐catenin signaling pathway were assessed. In animal experiments, the protective effects of GP on mouse hair follicles were evaluated. Results GP treatment enhanced cell viability, decreased melanocyte apoptosis, reduced intracellular ROS levels, increased melanin production, boosted tyrosinase and SOD activity, and potentially modulated the Wnt/β‐catenin signaling pathway. In animal experiments, GP significantly protected mouse hair follicles from H2O2‐induced damage. Conclusion The findings suggest that GP has potential as a treatment for hair graying by mitigating H2O2‐induced oxidative stress in melanocytes, highlighting its therapeutic potential in addressing oxidative stress‐related hair graying.

Hydrogen-rich Gynostemma pentaphyllum Makino distillate (HRGD) is produced by distilling G. pentaphyllum Makino, with the addition of hydrogen gas. This study sought to explore the pharmacological and biological impacts of HRGD on the generation of pro-inflammatory cytokines and mediators in macrophages. The cells were treated with various concentrations of HRGD (2, 4 and 8 μg/mL) in the absence or presence of lipopolysaccharide (LPS) (1 μg/mL) for 24 h. The results indicated that HRGD is an effective inhibitor of LPS-induced nitric oxide (NO•) production in RAW 264.7 cells: The NO• concentration was reduced dramatically after treatment with 8 μg/m98L HRGD (11.8 μM) compared to the LPS-induced group (28.4 μM). These inhibitory effects of HRGD included a dose-dependent decrease in the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) proteins. To evaluate the inhibitory effects of HRGD on other cytokines, we also measured cytokines tumor necrosis factor-α (TNF-α) level in the cell supernatants of LPS-stimulated RAW 264.7 macrophages by enzyme-linked immunosorbent assay. In this assay, HRGD significantly decreased the expression of TNF-α in a dose-dependent manner (p < 0.05). The study also performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on macrophages. HRGD did not display any cytotoxicity in this assay. The findings demonstrated that HRGD could modulate macrophage-mediated inflammatory functions such as the overproduction of cytokines, NO• and PGE2 without any cytotoxic.  

To assess the effects of microbial fermentation on Gynostemma pentaphyllum leaves (GPL), four probiotics were used to ferment GPL (FGPL) for 7 days. At different stages of fermentation, changes in the active components and biological activities of FGPL were determined. The findings suggest that short-term fermentation with probiotics can enhance both the content and bioactivity of active components in GPL. However, prolonged fermentation may lead to a decline in these aspects. Among them, the best effect was observed with SWFU D16 fermentation for 2 days. This significantly improved the total phenolic and total flavonoid content, antioxidant capacity, and inhibitory ability against α-glucosidase activity with an increase of 28%, 114.82%, 7.42%, and 31.8%, respectively. The high-performance liquid chromatography (HPLC) analysis results also supported this trend. Untargeted metabolomics analysis revealed metabolite changes between GPL and FGPL and the key metabolites associated with these functional activities. These key metabolites are mainly organic acids, flavonoids, carbohydrates, terpenoids, and other substances. KEGG analysis demonstrated that microbial metabolism in diverse environments and carbon metabolism were the most significantly enriched pathways. Among them, 3-(3-hydroxyphenyl) propanoic acid, d-glucose, gallic acid, gluconic acid, l-lactic acid, and l-malic acid were mostly involved in the microbial metabolism of diverse environmental pathways. In contrast, D-glucose, gluconic acid, and l-malic acid were mainly related to the carbon metabolism pathway. This study revealed the positive effect of probiotic fermentation on GPL and its potential metabolism mechanism, which could provide supporting data for further research.

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.

Background Gynostemma pentaphyllum (Thunb.), a traditional adaptogenic herb, is known for its bioactive components with potential anti-cancer properties. Acute myeloid leukemia (AML) progression is significantly influenced by Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3) signaling, while Wilms’ tumor 1 (WT1) serves as a key prognostic marker. This study investigates the anti-leukemia activities of active G. pentaphyllum leaf extracts and their components, focusing on the inhibition of FLT3 and WT1 activity. Methods G. pentaphyllum extracts were prepared through maceration, yielding three crude fractional extracts. The cytotoxicity of the extracts was screened against various leukemia cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The most cytotoxic extract was further fractionated and purified via column chromatography. The anti-proliferative and apoptotic induction activities of the active extract and its fraction were evaluated through cell cycle and apoptosis analyses using flow cytometry. Changes in mitochondrial membrane potential (ΔΨm) were assessed by spectrofluorometry. To confirm anti-leukemia activity, the expression levels of FLT3, WT1 and apoptotic-related protein were analyzed using Western blotting. The major active compounds within the active fractions were identified and characterized using Electrospray Ionization Mass Spectrometry (ESI-MS) and Nuclear Magnetic Resonance (NMR) spectroscopy. Results The ethyl acetate fractional extract (F-EtOAc) demonstrated the highest cytotoxicity, particularly against FLT3-overexpressing EoL-1 (IC 50  = 40.82 ± 0.8 µg/mL) and MV4-11 (IC 50  = 35.54 ± 4.1 µg/mL) AML cell lines. Fraction F10 was identified as the most active fraction, significantly inhibited FLT3 and WT1 protein expression and induced G0/G1 cell cycle arrest in a dose-dependent manner. Additionally, F10 induced dose-dependent apoptosis through disruption of ΔΨm, p53 up-regulation and caspase-3 activation. Further purification of F10 identified dehydrovomifoliol as its major bioactive compound. Conclusion These findings suggest that the ethyl acetate extract of G. pentaphyllum contains bioactive compounds with anti-leukemia potential, warranting further investigation to evaluate its efficacy against AML. Clinical trial number Not applicable.

Gynostemma (G.) pentaphyllum (Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum (GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal models of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and 6-hydroxydopamine. PD patients exhibit multiple symptoms, so PD-related research should combine neurotoxin models with genetic models. In the present study, we investigated the ameliorative effects of GP-EX, including gypenosides, on the cell death of dopaminergic neurons in the midbrain of A53T α-synuclein transgenic mouse models of PD (A53T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53T mice for 20 weeks. α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53T mice, which was reduced following treatment with GP-EX. Treatment with GP-EX modulated the reduced phosphorylation of tyrosine hydroxylase, extracellular signal-regulated kinase (ERK1/2), Bcl-2-associated death promoter (Bad) at Ser112, and c-Jun N-terminal kinase (JNK1/2) due to α-synuclein overexpression. In the A53T group, GP-EX treatment prolonged the latency of the step-through passive avoidance test and shortened the transfer latency of the elevated plus maze test. Gypenosides treatment exhibited the effects and efficacy similar to those of GP-EX. Taken together, GP-EX, including gypenosides, has ameliorative effects on dopaminergic neuronal cell death due to the overexpression of α-synuclein by modulating ERK1/2, Bad at Ser112, and JNK1/2 signaling in the midbrain of A53T mouse model of PD. Further studies are needed to investigate GP-EX as a treatment for neurodegenerative synucleinopathies, including PD. This study was approved by the Animal Ethics Committee of Chungbuk National University (approval No. CBNUA-956-16-01) on September 21, 2016.

Specific spatial information about medicinal plants is becoming an increasingly important part of their conservation. Gynostemma pentaphyllum (Thunb.) Makino is a traditional Chinese medical plant, and gypenosides is one of the main active components of G. pentaphyllum. In our research, many samples of G. pentaphyllum and the data of gypenosides content in these samples were collected from 43 sampling sites, and based on the Fuzzy Matter Element model (FME), the relationships between gypenosides content and 19 environmental variables were established. Then, the maximum entropy model was used to determine the relative importance of each environmental variable, and thus determine the most limiting habitat criteria. Finally, the weighted average method was applied to determine the potential distribution of G. pentaphyllum in China, which was based on the content of gypenosides. The results showed that the areas of marginally suitable and suitable habitats for G. pentaphyllum in China were approximately 1.2 × 106 km2 and 0.3 × 106 km2, respectively. The suitable habitats were mainly located in southern China, including Hunan, Hubei, Chongqing, Anhui, Jiangxi, Zhejiang, Shaanxi, and other regions. In conclusion, the FME model could accurately evaluate the habitat suitability of G. pentaphyllum, quantify the area of a suitable habitat, and analyze the spatial distribution.

Over the years, with the efforts of many researchers, the field of species distribution model (SDM) has been well explored. The model of fuzzy matter elements (FME), which, combined with GIS to predict species distribution, has received extensive attention since its emergence. Based on previous studies, this paper improved FME, extended the scope of the membership degree and habitat suitability index, and explored the unsuitable areas of species. We have enhanced the limitation effect of key variables on species habitats, making the operation of FME more consistent with biological laws. By optimizing the FME, it could avoid the accumulation of predicted errors with multi-variables, and make the predicted results more reasonable. In this study, Gynostemma pentaphyllum (Thunb.) Makino was used as an example. The experimental process used several major environmental variables (climate, soil, and terrain variables) to predict the habitat suitability distribution of G. pentaphyllum in China for its current and future period, which includes the period of 2050s (average for 2041–2060) and 2070s (average for 2061–2080) under representative concentration pathways 4.5 (RCP4.5). The results of the analysis showed that the model performed well with a high accuracy by reducing the redundancy of the environmental data. The study could relieve the reliance on a large database of environmental information and propose a new approach for protecting the G. pentaphyllum in unsuitable areas under climate change.

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.