Gynostemma

In Chinese the herb is jiaogulan (绞股蓝). The part used is the leaf and the other above-ground parts. It is classed as sweet and slightly bitter in taste and cool in nature, entering the Spleen and Lung channels. Its classical actions are to tonify qi, generate fluids, transform phlegm and stop cough.

The dried leaf is steeped as a tea and taken daily over long periods, more like a food than a prescription.

Jiaogulan appears in the Ming-dynasty Materia Medica for Famine Relief (1406) as a famine vegetable. Its standing as a tonic grew in the late twentieth century, after Japanese and Chinese analysis found ginseng-type saponins in the leaf.

In a 12-week RCT, 24 drug-naïve type 2 diabetics drinking 6 g/day of authenticated Gynostemma pentaphyllum tea or a placebo tea saw fasting plasma glucose fall by ~3.0 mmol/L (against 0.6 mmol/L on placebo) and HbA1c fall by ~2 percentage points (against 0.2), with a significant fall in HOMA-IR (insulin resistance) and no hypoglycemia ^{4Reference 4Huyen et al. · 2010RCTAntidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patients — randomised controlled trialView study →}.

A 2026 meta-analysis of eight clinical studies (584 patients) pooled a fasting-glucose reduction of −0.79 mmol/L and an HbA1c reduction of −1.01%, with monotherapy and longer courses performing best ^{3Reference 3Wang et al. · 2026Meta-analysisEfficacy and mechanisms of Gynostemma pentaphyllum in glycemic control — meta-analysis with reviewView study →}.

An independent systematic review of Ayurvedic/botanical antidiabetics reported a matching HbA1c effect of about −1% for the herb ^{5Reference 5Chattopadhyay et al. · 2022Meta-analysisEffectiveness and safety of Ayurvedic medicines in type 2 diabetes mellitus — systematic review and meta-analysisView study →}.

The proposed mechanisms include increased glucose uptake, reduced glucose output by the liver, and improved insulin secretion and sensitivity ^{3Reference 3Wang et al. · 2026Meta-analysisEfficacy and mechanisms of Gynostemma pentaphyllum in glycemic control — meta-analysis with reviewView study →}. In a human exercise trial, muscle AMPK Thr172 phosphorylation rose after supplementation ^{13Reference 13Nayyar et al. · 2023RCTGynostemma pentaphyllum increases exercise performance and alters mitochondrial respiration and AMPK in healthy males — randomised controlled trialView study →}.

Gap: trials are small, short and mostly East-Asian; standardized dosing is unsettled and the tea-versus-concentrated-extract question is unresolved.

A 2022 systematic review pooled 22 RCTs (2,407 dyslipidemia patients) and found Gynostemma comparable to statins, fibrates and n-3 fatty acids for triglycerides, total cholesterol and HDL-C. Added on top of those drugs, it gave an extra LDL-C reduction of ~0.57 mmol/L. Red yeast rice outperformed it head-to-head ^{6Reference 6Dai et al. · 2022Systematic reviewGynostemma pentaphyllum for dyslipidemia: a systematic review of randomized controlled trialsView study →}.

A separate meta-analysis confirmed reduced triglycerides and raised HDL-C, and its companion mouse work tied the lipid effect to changes in the gut microbiota and tryptophan metabolism ^{7Reference 7Li et al. · 2023Meta-analysisThe role of Gynostemma pentaphyllum in regulating hyperlipidemia — meta-analysisView study →}.

Both the leaf’s flavonoids (rutin, quercetin) and its saponins are thought to contribute.

Gap: review authors graded the evidence “very low to low certainty” — most trials carry risk-of-bias concerns, and the herb was weaker than red yeast rice.

In a single-blind randomised trial in 56 people with non-alcoholic fatty liver, adding 80 mL of Gynostemma extract to a diet program for four months significantly improved BMI, AST, insulin and HOMA-IR beyond diet alone ^{8Reference 8Chou et al. · 2006RCTThe add-on effects of Gynostemma pentaphyllum on nonalcoholic fatty liver disease — randomised controlled trialView study →}.

The 2013 Cochrane review of herbal medicines for fatty liver identified Gynostemma pentaphyllum among the single-herb products showing beneficial effects on liver enzymes and imaging, while noting that the underlying trials were at high risk of bias and used surrogate endpoints, never hard clinical outcomes ^{9Reference 9Liu et al. · 2013Systematic reviewHerbal medicines for fatty liver diseases — systematic reviewView study →}.

In methionine/choline-deficient NASH mice, the extract cut hepatic inflammation and lipid peroxidation, enriched beneficial gut flora (Akkermansia) and repressed hepatic NF-κB and TLR4/MyD88 signaling ^{10Reference 10Jiang et al. · 2024AnimalGynostemma pentaphyllum extract alleviates NASH in mice: inflammation and gut microbiota — mouseView study →}. Older rat models show protection against acetaminophen- and CCl4-induced liver injury ^{11Reference 11Lin et al. · 2000AnimalAntioxidant and hepatoprotective effects of Anoectochilus formosanus and Gynostemma pentaphyllum — ratView study →}.

Gap: every human result rests on enzymes, insulin markers and ultrasound — no biopsy-confirmed or long-term outcome data — and the protective rat study noted a biphasic, dose-sensitive response.

A 16-week double-blind RCT in 117 overweight adults found the ActivAMP Gynostemma extract significantly reduced total body weight, BMI, total fat mass and gynoid fat versus placebo, with men losing visceral fat specifically and plasma triglycerides, ALT and TNF-α differing between groups ^{12Reference 12Rao et al. · 2022RCTThe effect of an orally-dosed Gynostemma pentaphyllum extract (ActivAMP) on body composition — double-blind randomised placebo-controlled trialView study →}.

This is consistent with high-fat-diet mouse studies where the extract limited weight gain, lipid deposition and insulin resistance ^{7Reference 7Li et al. · 2023Meta-analysisThe role of Gynostemma pentaphyllum in regulating hyperlipidemia — meta-analysisView study →}.

The proposed mechanism is AMPK activation, the same pathway measured in human muscle in the exercise trial ^{13Reference 13Nayyar et al. · 2023RCTGynostemma pentaphyllum increases exercise performance and alters mitochondrial respiration and AMPK in healthy males — randomised controlled trialView study →}.

Gap: a single human body-composition trial, using one proprietary standardized extract; whether jiaogulan tea produces comparable fat-mass changes is untested.

Two human RCTs address physical performance. A double-blind placebo-controlled crossover in 16 healthy untrained men gave 450 mg/day of leaf extract (equivalent to 2.25 g of dried leaf) for four weeks and recorded improved 20-km time-trial performance, higher muscle oxygen flux, lower blood glucose and leptin, and earlier exercise-induced AMPK activation ^{13Reference 13Nayyar et al. · 2023RCTGynostemma pentaphyllum increases exercise performance and alters mitochondrial respiration and AMPK in healthy males — randomised controlled trialView study →}.

A separate 12-week RCT in 100 adults using a gypenoside-L-standardized extract raised VO2 max and O2 pulse, lowered perceived exertion and temporal fatigue, and increased blood eNOS ^{14Reference 14Ahn et al. · 2023RCTEffects of gypenoside-L-containing Gynostemma pentaphyllum extract on fatigue and physical performance — double-blind placebo-controlled randomised trialView study →}.

The samples are small, the durations short, and two different standardised extracts are involved. The effect measured is on performance and perceived exertion rather than on a clinical fatigue disorder.

Antioxidant activity is reported consistently, almost entirely in vitro and in animals. Leaf polysaccharides scavenge DPPH, hydroxyl, superoxide and ABTS radicals dose-dependently and, in diabetic and immunosuppressed mice, raise SOD, catalase, glutathione and GSH-Px while lowering malondialdehyde ^{15,16Reference 15Wang et al. · 2020AnimalAntioxidant and anti-inflammatory activities of an anti-diabetic polysaccharide from Gynostemma pentaphyllum — mouseView study →Reference 16Shang et al. · 2016AnimalImmunomodulatory and antioxidant effects of polysaccharides from Gynostemma pentaphyllum Makino in immunosuppressed mice — mouseView study →}.

Bioassay-guided fractionation points to phenolics such as a 3,4-dihydroxyphenyl glucoside and saponins including gypenoside L as the active radical-scavengers ^{17Reference 17Wang et al. · 2018In vitroBioassay-guided isolation of anticancer and antioxidant compounds from Gynostemma pentaphyllum — in vitroView study →}, and early rat work links this to the herb’s hepatoprotection ^{11Reference 11Lin et al. · 2000AnimalAntioxidant and hepatoprotective effects of Anoectochilus formosanus and Gynostemma pentaphyllum — ratView study →}.

No human study has measured an antioxidant endpoint directly.

The saponin fraction is anti-inflammatory across several animal models. In dextran-sulfate colitis mice, Gynostemma saponins reduced disease activity and colon damage by suppressing macrophage activation and NF-κB and STAT3 signaling ^{18Reference 18Wong et al. · 2017AnimalGynostemma pentaphyllum saponins attenuate inflammation by inhibition of NF-κB and STAT3 signaling — mouseView study →}.

Gypenoside A blunted Th2-driven airway inflammation in an asthma model ^{19Reference 19Huang et al. · 2022AnimalGypenoside A from Gynostemma pentaphyllum attenuates airway inflammation and Th2 cell activities in a murine asthma model — mouseView study →}.

In NASH mice the extract downregulated the TLR4/MyD88/NF-κB axis and TNF-α ^{10Reference 10Jiang et al. · 2024AnimalGynostemma pentaphyllum extract alleviates NASH in mice: inflammation and gut microbiota — mouseView study →}.

A diabetic-mouse polysaccharide study similarly raised IL-4/IL-10 and lowered TNF-α and IL-6 ^{15Reference 15Wang et al. · 2020AnimalAntioxidant and anti-inflammatory activities of an anti-diabetic polysaccharide from Gynostemma pentaphyllum — mouseView study →}.

The effect tracks isolated saponin and polysaccharide fractions rather than the leaf, and NF-κB suppression has not been shown in people.

In 72 healthy adults under chronic psychological stress, an ethanol leaf extract (200 mg twice daily, 8 weeks) lowered trait-anxiety scores by ~17% versus placebo. The other anxiety scales and the stress-hormone measures did not differ significantly from placebo ^{20Reference 20Choi et al. · 2019RCTSupplementation with Gynostemma pentaphyllum leaf extract reduces anxiety in healthy subjects with chronic psychological stress — randomised double-blind placebo-controlled trialView study →}.

In mice, gypenosides reduced LPS-induced anxiety- and depression-like behavior by dampening hippocampal and prefrontal neuroinflammation and suppressing the NLRP3 inflammasome ^{21Reference 21Guo et al. · 2024AnimalNeuroprotective effects of gypenosides on LPS-induced anxiety and depression-like behaviours — mouseView study →}.

Gap: a single small human trial with a modest, partly non-significant signal.

In rats, gypenosides dose-dependently reduced isoproterenol-induced myocardial infarct size and cardiac remodeling, lowering inflammatory cytokines and apoptotic caspases (−3, −6, −9) while shifting gut-microbiota composition ^{22Reference 22Zhang et al. · 2023AnimalCardioprotective effect of gypenoside against isoproterenol-induced cardiac remodeling in rats via inflammation and gut microbiota — ratView study →}.

In doxorubicin-stressed cardiomyocytes, gypenosides preserved mitochondrial function and rescued PINK1/parkin mitophagy via PI3K/Akt/GSK-3β/Mcl-1 signaling ^{23Reference 23Zheng et al. · 2024In vitroGypenosides exert cardioprotective effects by promoting mitophagy and activating PI3K/Akt/GSK-3β/Mcl-1 signaling — in vitroView study →}.

Gap: no human cardiac endpoint of any kind — the vasodilator and antihypertensive actions attributed to gynostemma rest on animal and mechanistic data, never on a clinical trial.

A 2024 review of rodent studies reports gypenosides active against depression, Parkinson’s, Alzheimer’s, stroke and optic-neuritis models, working through NF-κB, Nrf2, AKT and ERK1/2 pathways ^{24Reference 24Liang et al. · 2024ReviewNeuroprotective effects of gypenosides: a review on preclinical studies in neuropsychiatric disorders — reviewView study →}.

Gypenoside IX restored the Akt/GSK-3β axis and reduced tau hyperphosphorylation, amyloid-β production and cognitive deficits in an Alzheimer’s model ^{25Reference 25Lei et al. · 2023AnimalGypenoside IX restores Akt/GSK-3β and alleviates Alzheimer’s disease-like neuropathology and cognitive deficits — ratView study →}, and gypenosides eased neuroinflammatory depression-like behavior via NLRP3 suppression ^{21Reference 21Guo et al. · 2024AnimalNeuroprotective effects of gypenosides on LPS-induced anxiety and depression-like behaviours — mouseView study →}.

Gap: the review authors state that clinical research is essentially absent — findings are in-vitro and animal, using purified single gypenosides that may not reflect the whole leaf.

The immune findings come from the leaf polysaccharides, not the saponins. In cyclophosphamide-immunosuppressed mice, Gynostemma polysaccharides restored spleen and thymus indices, activated macrophage phagocytosis and NK cells, raised CD4+/CD8+ ratio and IL-2, and boosted antioxidant enzymes ^{16Reference 16Shang et al. · 2016AnimalImmunomodulatory and antioxidant effects of polysaccharides from Gynostemma pentaphyllum Makino in immunosuppressed mice — mouseView study →}.

A 2025 veterinary study found the extract acted as a mucosal vaccine adjuvant, raising antigen-specific IgG and secretory IgA against a pig diarrhea virus in mice ^{28Reference 28Zhang et al. · 2025AnimalImmunoenhancing effects of Gynostemma pentaphyllum extract on mucosal immunity against porcine epidemic diarrhea virus — mouseView study →}.

All of this work is in animals.

Gypenosides induce apoptosis in human colon-cancer cells through the mitochondrial pathway — raising ROS, Bax and p53, releasing cytochrome c and activating caspase-3 ^{27Reference 27Chen et al. · 2006In vitroGypenosides induced apoptosis in human colon cancer cells through the mitochondria-dependent pathways and activation of caspase-3 — in vitroView study →}. A 2016 review catalogues cell-cycle arrest, apoptosis, anti-invasion and anti-glycolysis effects across many cell lines, with a handful of xenograft and small clinical-formula reports ^{26Reference 26Li et al. · 2016ReviewAnti-cancer effects of Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan) — reviewView study →}.

Bioassay-guided work flags gypenoside L and ginsenoside Rd as the more cytotoxic constituents against A549 and MCF-7 lines ^{17Reference 17Wang et al. · 2018In vitroBioassay-guided isolation of anticancer and antioxidant compounds from Gynostemma pentaphyllum — in vitroView study →}.

Gap: in-vitro and xenograft work at concentrations no oral dose reaches, using purified constituents rather than the leaf.

Tolerability. Side effects in trials lasting from 4 weeks to 4 months have been mild and mostly digestive. The type 2 diabetes tea trial found no hypoglycaemia and no effects on kidney or liver tests ^{4,6,8Reference 4Huyen et al. · 2010RCTAntidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patients — randomised controlled trialView study →Reference 6Dai et al. · 2022Systematic reviewGynostemma pentaphyllum for dyslipidemia: a systematic review of randomized controlled trialsView study →Reference 8Chou et al. · 2006RCTThe add-on effects of Gynostemma pentaphyllum on nonalcoholic fatty liver disease — randomised controlled trialView study →}. A systematic review judged use for more than eight weeks to be safe on current data ^{6Reference 6Dai et al. · 2022Systematic reviewGynostemma pentaphyllum for dyslipidemia: a systematic review of randomized controlled trialsView study →}.

Blood sugar. Gynostemma lowers blood glucose, so it may add to the effect of antidiabetic drugs, and blood sugar should be monitored when the two are combined ^{3,4Reference 3Wang et al. · 2026Meta-analysisEfficacy and mechanisms of Gynostemma pentaphyllum in glycemic control — meta-analysis with reviewView study →Reference 4Huyen et al. · 2010RCTAntidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patients — randomised controlled trialView study →}.

Drug metabolism. In laboratory tests, gypenosides inhibited CYP2D6 strongly and CYP2C8, CYP3A4 and CYP2C9 more weakly ^{30Reference 30He et al. · 2013In vitroInhibitory effects of gypenosides on seven human cytochrome P450 enzymes — in vitroView study →}. No animal or human study has tested whether this changes drug levels.