IngredientsGypenosides (also rendered as gypenoside, gynosaponins, or, in Chinese pharmacopeial contexts, jiaogulan total saponins) are a family of triterpenoid saponins constituting the principal bioactive fraction of Gynostemma pentaphyllum (Thunb.) Makino — a climbing perennial vine in the family Cucurbitaceae. Gypenosides are the main active components of Gynostemma pentaphyllum, a climbing plant in the family Cucurbitaceae. The plant is known by numerous vernacular names: jiaogulan in Mandarin Chinese (literally "twisting-vine orchid"), amachazuru (sweet tea vine) in Japanese, and colloquially as "Southern ginseng" or "immortality herb" in English-language contexts. As a traditional Chinese medicinal plant, G. pentaphyllum is commonly referred to as "Southern ginseng" and possesses significant medicinal value due to its content of ginsenosides and other structurally similar dammarane-type saponins.
Gynostemma pentaphyllum (Thunb.) Makino is a creeping perennial herb that belongs to the family Cucurbitaceae. This species is predominantly distributed in tropical Asia, particularly in the southern regions of the Qinling Mountains and the moist forests of the Yangtze River Basin in China. It is widely distributed in China, Korea, Japan, and Southeast Asian countries.
Gypenosides can be divided into two main structural families: the dammarane-type and the cucurbitane-type. The dammarane-type are by far the more abundant and better-studied group. Previous chemical investigations revealed dammarane-type saponins named gypenosides as the major bioactive constituents of G. pentaphyllum, and more than 300 gypenosides with diverse structures have been characterized to date. More recent analytical work using two-dimensional liquid chromatography has substantially expanded this catalogue: in total, 1,108 saponins were characterized, among which 588 were accurately characterized, with 574 identified in the reference herbal drug and 700 in the mixed commercially available samples.
A defining structural feature is the gypenosides' relationship to the ginsenosides of Panax ginseng. The dammarane-type saponins include compounds that are identical to those found in ginseng — ginsenosides Rb1, Rb3, F2, Rg3, Rc, Rd, malonyl-Rb1, and malonyl-Rd — as well as those that are chemically similar. Specifically, gypenosides III, IV, VIII, XII and malonyl gypenosides III and VIII are identical to ginsenosides Rb1, Rb3, Rd, F2, and malonyl ginsenosides Rb1 and Rd. These numbers are about five or six times more than ginsenosides, well-known major bioactive components of Panax species.
Representative major saponins identified by quantitative methods in tetraploid leaf material include gypenosides 1 and 2 (C47H76O18), 3 (C47H76O17), and 4 (C46H74O17). General dammarane-type gypenoside scaffolds carry sugar residues (glucose, rhamnose, xylose) at specific positions on the aglycone backbone: the general structure of dammarane-type gypenosides has R1/R2 = glucose or rhamnose, and R3 = glucose or xylose.
The primary commercial source of gypenosides is the dried aerial parts — leaves and stems — of G. pentaphyllum. The chemical constituents of Gynostemma pentaphyllum vary drastically among different origins and varieties. Ploidy level also influences yield: the tetraploid whole-plant botanical had the highest total saponin content of 227.1 mg gypenoside equiv/g. Commercially available preparations have been found to show great composition variation. The commercially available samples showed great composition variation.
Other Gynostemma species — including G. longipes and G. laxum — have been used as alternatives in ethnomedicine in Vietnam and other Asian countries, and also yield dammarane-type saponins, though their profiles differ from G. pentaphyllum. Other species of the same genus such as G. longipes and G. laxum have been used as alternatives to G. pentaphyllum in ethno-medicine in Vietnam and other Asian countries.
It has been widely used as an herbal tea and traditional Chinese medicine (TCM), such as total Jiao-gu-lan saponin tablet, and Jiao-gu-lan tea. Chemical research indicates G. pentaphyllum primarily contains active ingredients including saponins, polysaccharides, and flavonoids. Dosage forms in current commercial and clinical contexts include standardised whole-herb extracts (with gypenoside content specified as a percentage), isolated total-saponin fractions, encapsulated powders, and herbal teas made from dried leaves. Heat-processing of the extract alters the gypenoside profile and has been used in at least one clinical trial formulation (see Obesity/Body Composition section below).
As a well-known edible and medicinal plant, G. pentaphyllum has a long history of application in oriental medicine since the Ming dynasty. The famous classical book of Chinese material medica, Compendium of Materia Medica, first recorded the usage and curative effect of G. pentaphyllum. It was first mentioned in 1406 CE by Zhu Xiao, who recommended it as a survival food. In 1578, it was identified by Li Shizhen in his Compendium of Materia Medica as a medicine for treating edema, tumors, and trauma.
It has been utilized for centuries in China for culinary and medicinal purposes. G. pentaphyllum was first recognized as an edible wild herb during the famine of the Spring and Autumn Periods. Initially and traditionally, G. pentaphyllum was a kind of tea consumed by people for its pleasant taste and weight-loss efficacy.
The local people of the mountainous regions of southern China and northern Vietnam, who were familiar with Gynostemma, called it the immortality herb, as a large number of people who lived to be over 100 years old reported consuming it regularly instead of green tea. They used the tea in the morning to energize and a cup in the evening to unwind, relax, and promote sleep.
In Japan, it is called amachazuru or "sweet tea vine" because its leaves have been used as a dietary sweetener.
Modern research from 1970 studied Gynostemma as a possible sugar substitute. It was during this period of investigation in Japan that the saponin nature of the plant's active constituents was first characterised scientifically. Since Takemoto and his colleagues continued to report the structures of 21 saponins isolated from this species (Takemoto et al., 1977, 1979, 1980), more than 300 saponins and sapogenins were isolated and characterized from Gynostemma and its processed samples. The plant has since been used in TCM as a registered herbal medicine; for example, products based on crude saponins from G. pentaphyllum have been used clinically in China and have been described as having insignificant toxicity.
While gypenosides are the primary focus of pharmacological research, the whole plant also contains additional bioactive constituents. G. pentaphyllum contains various bioactive compounds including saponins, flavonoids, amino acids, and vitamins. Among these, gypenosides are recognized as the primary active ingredients, which exhibit antioxidant properties along with anti-cancer effects, lipid-lowering capabilities, and immune-enhancing activities.
Gypenosides significantly inhibit the nuclear translocation of nuclear factor-κB and activator protein 1 (c-Fos and c-Jun) through down-regulating the phosphorylation of their upstream IκB kinase and mitogen-activated protein kinases (MAPKs), especially c-Jun N-terminal kinase and extracellular regulated protein kinase (JNK and ERK), but not that of the p38 MAPK. In macrophage cell models, pretreatment of gypenosides reduced mRNA expressions of the proinflammatory mediators in LPS-stimulated RAW264.7 macrophage cells, such as IL-6, IL-1β, COX-2, and TNF-α in a dose-dependent manner.
Activation of AMP-activated protein kinase (AMPK) is a central mechanism through which gypenosides regulate energy metabolism. Gypenosides attenuate hepatic steatosis and intestinal barrier injury in MAFLD rats via the AMPK and TLR4/nuclear factor kappa B (NF-κB) pathways, providing a potential treatment for MAFLD patients.
Studies have demonstrated that gypenosides reduce triglyceride levels through PPAR/UCP-1/PGC-1α/PRDM16 and (SREBP-1c)-ACC/FAS-CPT1 signalling pathways, while also exerting cholesterol-lowering effects via (SREBP-2)-HMGCR, PCSK9-LDLR, and bile acid mechanisms. The PCSK9 pathway is of particular interest because gypenosides exhibit multimodal cardioprotective effects through NF-κB/NLRP3 pathway modulation, cholesterol efflux enhancement, and mitochondrial function optimisation.
Gypenosides possess therapeutic properties in mitigating diabetes mellitus by regulating blood glucose levels and insulin production. Gypenosides can modulate various key pathways associated with diabetes pathogenesis, including PI3K/Akt, PPARγ, NF-κB, AMPK and PDX1, hence contributing to their antidiabetic properties.
Pharmacological studies have discovered that gypenosides can modulate various major signalling pathways like NF-κB, Nrf2, AKT, ERK1/2, contributing to the neuroprotective properties.
In the past two decades, a growing body of evidence has demonstrated that gypenosides are crucial for the regulation of metabolic homeostasis, the reduction of oxidative stress and inflammation, the protection of the cardiovascular and hepatic systems, and the exhibition of anti-cancer potential. Antioxidant effects are mediated in part via the Nrf2 pathway and through direct free-radical scavenging.
Scientific studies have shown that gypenosides target cancer cells via different mechanisms and pathways, such as inhibiting the cancer cell initiation, inducing cell apoptosis, inhibiting the cell repair mechanism, and suppressing the migration of cancer cells to neighbouring tissues.
The most methodologically robust human trial on gypenosides is the 2014 Actiponin trial published in Obesity (Wiley). The effects of Actiponin — a heat-processed Gynostemma pentaphyllum extract — on body weight, fat loss, and metabolic markers of Korean participants were investigated in a 12-week, randomized, double-blind, placebo-controlled clinical trial. Obese participants (BMI ≥ 25 kg m−2 and WHR ≥ 0.90 for male or ≥ 0.85 for female) who had not been diagnosed with any disease were recruited. The 80 subjects were randomly divided into Actiponin (n = 40, 450 mg day−1) and placebo (n = 40) groups. Outcomes included measurement of efficacy (abdominal fat distribution, anthropometric parameters, and blood lipid profiles) and safety (adverse events, laboratory test results, electrocardiogram data, and vital signs). During 12 weeks of Actiponin supplementation, total abdominal fat area, body weight, body fat mass, percent body fat, and BMI were significantly decreased (P = 0.044, P < 0.05, P < 0.0001, P < 0.0001, and P < 0.05, respectively) in the Actiponin group.
Evidence strength: This single double-blind RCT in a Korean cohort (n = 80) represents the strongest human evidence available for a gypenoside-containing extract on adiposity. The small sample size, single ethnic group, single proprietary extract, and short duration (12 weeks) limit generalisability. Independent replication has not yet been published.
Clinical trials have shown that gypenosides can lower lipid levels by inducing satiety and reducing appetite and regulating energy homeostasis. Interests in understanding the cardiovascular properties of gypenosides appear to be mounting. The anti-hyperlipidaemic effect has been observed in human and animal studies, with an efficacy comparable to most current natural products, suggesting safety and effectiveness through chronic clinical treatment of hyperlipidaemia.
In animal models, prolonged administration of gypenosides extract significantly reduces serum cholesterol levels, improves cardiac function, and lowers the incidence of atherosclerosis. Multiple molecular pathways have been confirmed in mouse studies: G. pentaphyllum saponins regulate triglyceride metabolism mainly through the PPAR/UCP-1/PGC-1α/PRDM16 and (SREBP-1c)-ACC/FASN-CPT1 pathways. It regulates cholesterol metabolism mainly through the (SREBP-2)-HMGCR, PCSK9-LDLR, and bile acid biosynthetic pathways.
Regarding cholesterol gallstones, gypenosides reduced total cholesterol levels and increased bile acid levels in bile, as well as reducing the Bile Acid Hydrophobicity Index and Cholesterol Saturation Index in gallbladder bile — findings from a mouse model. At present, the effects of gypenosides on cholesterol gallstones in humans remain unknown. Clinical trials to explore whether gypenosides can alter biliary lipid composition in patients are ongoing.
Evidence strength: The mechanistic evidence from preclinical studies is substantial. Human clinical data are limited and have not been published in sufficient quantity or methodological detail to establish a definitive evidence base. The lipid-lowering effects remain an active area of clinical investigation.
Gynostemma pentaphyllum has a longstanding history of usage in traditional oriental medicine, particularly for the treatment of diabetes mellitus. Gypenosides were found to exhibit antidiabetic effects. Research has shown that gypenosides possess therapeutic properties in mitigating diabetes mellitus by regulating blood glucose levels and insulin production. Gypenosides can modulate various key pathways associated with diabetes pathogenesis, including PI3K/Akt, PPARγ, NF-κB, AMPK and PDX1.
In an animal study investigating the mechanism of action, the aim was to explore the mechanism of action of gypenosides on type 2 diabetes mellitus and non-alcoholic fatty liver disease in rats. Sixty rats were randomly divided into a healthy group, an untreated disease model group, and GP-treatment groups. The study involved the evaluation of biochemical parameters, including serum AST, ALT, blood glucose, triglycerides, and total cholesterol. Intervention with gypenosides significantly decreased the levels of aspartate aminotransferase, alanine aminotransferase, blood glucose, insulin, triglycerides, and total cholesterol in T2DM-NAFLD model rats, down-regulated the expression of TNF-α, NF-κB, PPARγ, and CYP1A1 mRNA, decreased the infiltration of liver fats, and reversed the histopathological changes in a dose-dependent manner. Doses tested in this rat study were oral doses of 200, 400, and 800 mg/kg per day.
A 2025 mouse study used doses of 200, 100, or 50 mg/kg for 4 weeks in type 2 diabetes mellitus mouse models. Collectively, preclinical evidence establishes gypenosides as multi-target therapeutic agents that regulate glucose homeostasis, preserve pancreatic function, and prevent diabetic complications.
Evidence strength: This review outlined the advancements in the preclinical studies of gypenosides' pharmacological properties on diabetes mellitus and their potential mechanism of action, while noting the lack of clinical evidence for gypenosides' efficacy. There is a paucity of research on gypenosides in clinical settings, with existing studies being mainly conducted on animal models and in vitro. The antidiabetic evidence base is currently preclinical only.
Gypenosides, extracted from the traditional Chinese herb Gynostemma pentaphyllum, have been used to treat metabolic disorders, including lipid metabolism disorders and diabetes. Although recent studies have confirmed their beneficial effects in non-alcoholic fatty liver disease (NAFLD), the underlying therapeutic mechanism remains unclear. In mouse studies using high-fat diet models, gypenosides decreased serum lipid levels, liver index, and liver fat accumulation in mice. Principal component and heatmap analyses indicated that gypenosides significantly modulated the changes in the expression of genes associated with HFD-induced NAFLD.
One controlled clinical study in humans with NAFLD was identified: in a controlled clinical trial on 56 people with non-alcoholic fatty liver disease, the group treated with G. pentaphyllum extract in addition to diet showed significant improvements in body mass index, liver enzyme levels, insulin levels, and insulin resistance index after 6 months. This represents modest but notable human evidence. Mechanistically, gypenosides attenuate hepatic steatosis and intestinal barrier injury in MAFLD rats via the AMPK and TLR4/NF-κB pathways.
Evidence strength: Preclinical mechanistic data are robust. The single controlled human trial in NAFLD (n = 56) provides preliminary evidence but is limited in sample size and has not been independently replicated in high-quality RCTs.
Gypenosides have demonstrated significant cardioprotective qualities in the context of cardiovascular diseases. They are crucial in the prevention and treatment of several cardiovascular diseases by modulating lipid metabolism, reducing blood pressure, enhancing endothelial function, and preventing atherosclerosis. The dammarane saponins, namely gypenosides, isolated from G. pentaphyllum, are believed to be the active principles responsible for its biological activities and reported clinical efficacy in the treatment of cardiovascular diseases and related disorders.
In the context of diabetic cardiomyopathy, gypenosides have been shown preclinically to reduce reactive-oxygen-species-mediated NLRP3 inflammasome activation in cardiomyocyte models. For myocardial ischaemia, gypenoside A mitigates cardiac injury through AMPK pathway activation and miR-143-3p downregulation.
Evidence strength: Predominantly preclinical (animal and cell-based). Direct randomised clinical trial evidence for cardiovascular endpoints is absent at the time of this writing.
Preclinical studies have demonstrated the therapeutic effects of gypenosides in alleviating neuropsychiatric disorders such as depression, Parkinson's disease, Alzheimer's disease, secondary dementia, stroke, optic neuritis, and others. Regarding depression specifically, under chronic unpredictable mild stress (CUMS) conditions, seven-day gypenoside treatment reduced depressive behaviours and hippocampal proinflammatory cytokines (IL-1β, IL-6, TNF-α) in mice.
Evidence strength: There is a dearth of clinical research on gypenosides, with current investigations on the compounds being mainly conducted in vitro and on animals. All neuroprotection evidence is currently preclinical.
Multiple in-vitro and some in-vivo animal studies have examined gypenosides' anti-proliferative effects. In colorectal cancer cell lines (SW-480), gypenosides decreased the percentage of viable cells. Previous studies have demonstrated that the cytotoxic effect of gypenosides on normal peripheral blood mononuclear cells (PBMC) was much less. In lung cancer cell lines, gypenoside-induced cell cycle arrest via inhibition of cyclin E and induction of apoptosis via activation of caspases-3 and -9 has been reported. Gypenoside L and ginsenoside Rd displayed the highest inhibition of tumour cell proliferation of A549 and MCF-7 cell lines.
Evidence strength: All anti-cancer evidence is from in-vitro cell studies and animal models. No human clinical oncology trial evidence exists. These findings are preliminary and exploratory only.
A 12-week randomised, double-blind, placebo-controlled trial demonstrated that a gypenoside L-containing extract alleviates exercise-induced fatigue without adverse effects, underscoring its therapeutic potential (Ahn et al., 2023).
Evidence strength: A single small RCT. Replication is required before firm conclusions can be drawn.
Dosages reported in the scientific literature vary substantially by study design, formulation, and species:
Obstacles such as limited oral bioavailability, a lack of standardised extracts, and insufficient clinical data restrict the translational potential of gypenosides.
Products based on crude saponins from G. pentaphyllum have been used clinically in China and have been described as having insignificant toxicity. Acute (0.8 g/kg) and subacute (10–50 mg/kg) toxicity studies of GP-75 in mice demonstrated no instances of mortality or significant toxicity. In randomised controlled trials, the incidence of adverse events of gypenosides was substantially lower than that of conventional lipid-lowering drugs, as indicated by the most recent systematic review. Additionally, no serious adverse reactions were observed after continuous use of gypenosides for more than extended periods, according to this review.
Current evidence suggests that human safety data for gypenosides are limited to extracted preparations.
A significant pharmacological safety concern relates to cytochrome P450 (CYP) enzyme inhibition. An in-vitro study in human liver microsomes found that gypenosides showed the strongest inhibition of CYP2D6, followed by CYP2C8, CYP3A4, and CYP2C9. The IC50 values were 1.61 μg/mL (CYP2D6), 20.06 μg/mL (CYP2C8), 34.76 μg/mL (CYP3A4/midazolam), 46.73 μg/mL (CYP3A4/testosterone), and 54.52 μg/mL (CYP2C9), respectively. Conversely, gypenosides (even 100 μg/mL) have no significant inhibitory effects on CYP1A2, CYP2B6, and CYP2C19 in vitro, and had only weak inhibitory effects on CYP2C8, CYP3A4, and CYP2C9.
In East Asia, gypenosides are frequently consumed in combination with prescription medicines, but the risk has not been fully evaluated. The CYP2D6 inhibition identified in vitro raises the possibility of clinically relevant pharmacokinetic interactions with co-administered drugs that are substrates of this enzyme — a broad category that includes certain opioids, antidepressants, antipsychotics, beta-blockers, antiemetics, antiarrhythmics, and antihistamines. However, the clinical relevance of the in-vitro findings requires in-vivo confirmation.
Caution has been noted regarding potential interactions with antiplatelet or anticoagulant medications, immunosuppressants, and diabetes medications, based on the pharmacological properties of gypenosides. These interactions have not been formally characterised in controlled human studies.
In the Actiponin obesity RCT, no serious adverse events were recorded in either treatment or placebo groups across the 12-week trial period. A 12-week randomised, double-blind, placebo-controlled trial demonstrated that a gypenoside L-containing extract alleviates exercise-induced fatigue without adverse effects.
The pharmacokinetics and pharmacodynamics of gypenosides in the human body are still not well understood. The beneficial and adverse effects, including toxicity of gypenosides in animal models, should be researched meticulously. Long-term human safety studies with standardised, well-characterised gypenoside preparations remain an important gap in the literature.
The scientific literature on gypenosides is extensive in volume but uneven in quality. Several important limitations recur across the body of evidence:
In the past two decades, a growing body of evidence has demonstrated that gypenosides are crucial for the regulation of metabolic homeostasis, the reduction of oxidative stress and inflammation, the protection of the cardiovascular and hepatic systems, and the exhibition of anti-cancer potential. However, the transition from promising preclinical compound to evidence-based therapeutic agent requires substantially more rigorous human clinical investigation.
Health conditions that Gypenoside may help support.
Gypenosides are the saponin bioactives of Gynostemma pentaphyllum and among the most potent natural AMPK activators, with human RCT evidence showing significant improvements in glucose metabolism, lipid profiles, and body composition — key metabolic aging targets.
Gypenosides are the bioactive saponin constituents of Gynostemma pentaphyllum responsible for insulin-sensitizing effects. They directly activate AMPK (including the specific damulin A and B isoforms), improving glucose uptake, reducing hepatic glucose production, and lowering insulin resistance markers in both animal models and clinical studies.
Gypenosides are the saponin glycosides in Jiaogulan (Gynostemma pentaphyllum) structurally analogous to ginsenosides. They are responsible for the plant's adaptogenic and anti-fatigue properties used in traditional Chinese medicine to support mental vitality.
Gypenosides are the bioactive saponins in jiaogulan (Gynostemma pentaphyllum), used in traditional Chinese medicine as an adaptogen for endurance, stamina, and anti-fatigue. Animal studies and limited human data show gypenosides activate AMPK pathways, improve mitochondrial function, and delay fatigue during exercise. Traditional use as a tea for longevity and physical endurance is well-established in southern China.
Gypenosides are the primary bioactive saponins of Jiaogulan (Gynostemma pentaphyllum), structurally related to Panax ginseng ginsenosides, with adaptogenic, antioxidant, and immunomodulatory properties relevant to post-viral fatigue and immune recovery. They activate AMPK and support mitochondrial biogenesis.
Triterpenoid saponins from Gynostemma pentaphyllum (jiaogulan), a herb with documented anxiolytic properties in preclinical models and traditional Chinese medicine use as an adaptogen. Included in a systematic review of adaptogenic plants studied in RCTs for stress, alongside Ashwagandha and Rhodiola.
Body systems that Gypenoside may help support.
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