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Gynostemma pentaphyllum

Gynostemma pentaphyllum (Southern Ginseng) is a herb given Ginseng status although not related to Panax Ginseng. It appears to share some saponins though, and is investigated for similar effects as True Ginseng.

Our evidence-based analysis on gynostemma pentaphyllum features 109 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Research Breakdown on Gynostemma pentaphyllum

1Sources and Composition


Gynostemma pentaphyllum (Southern Ginseng) of the Cucurbitaceae family is a plant that has usage in Traditional Chinese Medicine (where it is referred to as Jiao Gu-lan) for cough, wheeze, chronic bronchitis and infectious hepatitis. It seems to possess ginsenoside-like saponins despite not being related to Panax Ginseng (True Ginseng),[2] and tea that contains higher level of Panax's ginsenosides are sweeter (which make it fairly popular).[3] It is considered a longevity herb[4] with herbs in the Gynostemma genus referred to as herbs of immortality.[5][6]

A herb that itself has a traditional use mostly as a tea, it has sometimes been called 'Cheap Ginseng' since it has many of the same effects and was cheaper (Panax Ginseng has a history where the supply was sequestered by the upper classes, which raised the market value)


The main Gypenoside class of bioactives (those unique to Gynostemma Pentaphyllum) include:

  • Gylongiposide I[7]

  • Gypensapogenin A-D[2] gypensapogenin E-G[8]

  • Gypenbiosides A and B[9]

  • Gypenosides GC1 to GC7 (2α,3β,12β,20(S)-dammarane type structure)[10]

  • Gypenoside III at 0.9% dry weight (a glycoside of Ginsenoside Rb1), IV (a glycoside of Ginsenoside Rb3), VIII at 0.4% (Ginsenoside Rd), XII (Ginsenoside F2)[11][12][13]

  • Malonyl Gypenosides III and VIII (Malonyl Ginsenosides Rb1 and Rd, respectively)[11]

  • Gypenoside LXXIV (G74),[14] Gypenoside XLIX, and Gypenoside A (XLIII)[15]

  • Gymnemaside VI[10]

  • Gynostemosides A-E (Megastigmane compounds based on the backbone of 3,4-dihydroxy-5,6-dihydro-β-ionol)[16]

  • Gynoside A, ocotillone type triterpenoid ((20S,24S)-20,24-epoxy-12,25-dihydroxy-dammaran-3-yl-O-β-D-glucopyranosyl(1→2)-β-D-xylopyranoside)[17] as well as B-E[18]

  • Phanoside, a term used to refer to four isomers of a Gypenosapogenin glycoside[19][20]

Gypenosides are Gypenosapogenin or Ginsenoside structures (the former pictured below) attached to sugars; as such, they are Gypenosapogenin or Ginsenoside Glycosides (Glycoside merely being a term to refer to 'attached to sugar(s)'; a storage form of sorts)

With other notable saponin structures as:

  • Ginsenosides Rb1, Rb3, Rd and F2 (all found in Panax Ginseng)[3]

  • 3β,20(S),21-trihydroxydammar-24-ene (aka. H6) with the glycoside of Gypenoside XLIX,[21] structurally related 3β,20ξ,21-trihydroxydammar-23-ene glycosides[22]

  • Damulin A and B, ranging from 0.09-0.1% dry weight and increasing up to 0.7-0.9% when heat treated (autoclaving at 121°C);[23] a heat treated extract with high Damulin content being called 'Actiponin'.[23] The true names of these compounds being diglycosides of 2α,3β,12β–trihydroxydammar-20(22)-E,24-diene and 2α,3β,12β-trihydroxydammar-20,24-diene, respectively[24]

  • (20S)-dammarane-24(25)-ene-3β,20,21-tetrol and (20S,24S)-dammarane-25(26)-ene-3β,12β,20,24-tetrol[8]

  • Dammarane-(E)-20(22)-ene-3β,12β,25-triol and 20(S)-dammarane-25(26)-ene-3β,12β,20-triol[8]

  • 20(S)-protopanaxadiol[8]

  • (23S)-3β-dihydroxyl-dammarane-4-ene-21-oic acid-21, 23-lactone[8] (also found in Machilus yaoshansis[25])

  • (20S,23S)-3β,20-dihydroxyldammarane-24-ene-21-oic acid-21, 23-lactone (and its R,R enantiomer)[8]

  • 3β-hydroxyetio-17β-dammaranic acid[8]

Some saponins in Gynostemma Pentaphyllum are literally the same Ginsenosides found in Panax Ginseng, with other saponins being more generalized among herbs

And various other non-saponin compounds:

  • Carotenoids (cis-neoxanthin, violaxanthin, auoxanthin, luteoxanthin, lutein, α-carotene and β-carotene)[26]

  • Chlorophyll compounds (Chlorophyll A (113.8ug/g) A'(11.0ug/g) B (287.9ug/g) and B'(11.1ug/g), Pheophytin A (2508.3ug/g) A'(111.2ug/g) B(319.6ug/g) B'(13.2ug/g); hydroxy derivatives including hydroxypheophytin A (88.6ug/g) A'(66.5ug/g) B(11.2ug/g) B'(8.5ug/g) and hydroxychlorophyll A (23.8ug/g) and B (15.0ug/g)[26][27] as well as pyropheophytin A (76.0ug/g)[27]

  • Ombuine (Ombuin-3-O-β-D-glucopyranoside)[28]

  • Caffeic Acid[29]

  • Allantoin[7]

  • Vitexin[7]

  • Quercetin as di(rhamno)-hexoside (548.3mcg/g) and rhamnohexoside (1249.6mcg/g)[29][30] and in the leaves of diploids (9.64-12.1mg/g) and tetraploids (0.82-1.27mg/g)[31]

  • Kaempferol as rhamno-hexoside (1792.9-2416.5mcg/g), 3-O-rutinoside (429.7mcg/g), and free form.[29][30] Kaempferol 3-O-di-p-coumaroylhexoside has also been detected[31] 

  • Rutin (1602.8mcg/g)[30][29] and in the leaves in the range of 18.97-23.03mg/g for diploid samples and 9.74-11.19mg/g for tetraploid[31]

  • 3,5,3′-trihydroxy-7,4′-dimethoxyflavone (From the leaves)[4]

  • Selenium ranging from 0.094-0.265mg/kg, with one outlier at 1.730[32]

  • Calcium (1384−34070mg/kg) and Magnesium (783−7739mg/kg)[33]

  • Some trace minerals[33]

With some bioactive polysaccharides:

  • GPP1a[34]

  • GPP2b[34]

  • GPP3a[34]

  • PGSP at 1.5% dry weight; water-soluble and a structure of glucose:galactose:arabinose:rhamnose:galacturonic acid:xylose:mannose:glucuronic acid in a 23.2:18.9:10.5:7.7:4.7:3.9:3.1:1.2 ratio[35]

In general, ethanolic root extracts are concentrated for saponin and triterpenoid structures (first two subsections) while hot water extracts of the leaves (teas) are concentrated for flavonoids; there will still be flavonoids in the roots and saponins in the leaves though; the polysaccharides are in the root mostly and confer a caloric content as they are carbohydrates

When assessing overall quantities of molecule classes, saponins have been found in the range of 64.57-132.6mg/g (6.4-13.2% Saponins wet weight) which are concentrated in ethanolic extracts.[32] Of these, 2.4% (total weight of all parts) are dammarane-type saponins, with 75% of these dammarane-type saponins belonging to the class of Gypenosides (so effectively, Gynostemma Pentaphyllum is around 2% Gypenosides by weight if not otherwise concentrated).[15] Unlike most saponin-containing plants, the leaves appear to confer the highest concentration of saponins with the roots being lowest (stem intermediate).[36]


2.1Enzymatic Interactions

The whole plant of Southern Ginseng has been found to reverse Multidrug Resistance, where P-Glycoprotein resistance to colchine (no effect on vinblastine or taxol) was reversed approximately 15-fold in vitro in the presence of 0.1mg/mL total Gypenosides, which was increased to 42-fold when purified further effectively abolishing the resistance.[37] A later study isolated 3β,20(S),21-trihydroxydammar-24-ene (dubbed H6) found that while it did not exert toxicity below 50uM, lower concentrations were able to augment Vincristine-induced cytotoxicity, reducing the IC50 of Vincristine when H6 was at 5-20uM to the range of 2-9% of Vincristine alone.[21] Additionally, this study suggested that H6 may induce P-gp (via ATPase) and inhibit MRP1 (via STAT3 inhibition) in KB/VCR cells.[21]

Appears to interact with a drug efflux protein potently, and may have a role in augmenting some chemotherapies. The practical significance of this has not been tested in a living system yet


3.1Parkinson's Disease

In cultured substantia nigra dopaminergic neurons (highly associated with the pathology of Parkinson's Disease), 1-methyl-4-phenylpyridinium ion (MPP+) induced damage is attenuated with Gypenosides at 50-200ug/mL, with more efficacy when pretreated rather than posttreated.[38] 200ug/mL was associated with almost normalization of anti-oxidant enzymes and pro-oxidative biomarkers (MDA, ROS) when pretreated.[38]

Protection against MPTP have been noted in vivo in rats associated with less oxidative damage,[39] and has been noted against hydroxydopamine (a pro-oxidative derivative of dopamine) following oral administration of 10-30mg/kg of the ethanolic extract of Gynostemma Pentaphyllum, where the cell survival that was reduced to 40.1% (relative to 100% of control) was attenuated to 67.4% and 75.8% at the two doses over 28 days (with a similar degree of preservation of catecholamines, which were reduced in toxin control).[40]

Appears to be protective of a cluster of neurons that are involved in Parkinson's Disease, with this protection likely mediated via anti-oxidant effects (and more effective when pre-loaded). No human studies, but has shown efficacy in mice at relatively low doses


An in vitro study on hippocampal cells deprived of oxygen and glucose noted that an ethanolic extract of Gynostemma pentaphyllum appears to preserve evoked field potential amplitude almost wholly when preincubated for 120 minutes prior to experimentation with no protective effect if incubated 60 minutes prior to insult.[41] At 60ug/mL ethanolic extract, a two-fold induction of Superoxide Dismutase (SOD) protein content was noted with a 20% increase in glutathione peroxidase after 48 hours incubation; these changes were independent of changes in DCFH fluorescence or H2O2 concentration, suggesting the increase in anti-oxidant enzyme defense was independent of changes in the basal oxidative balance.[41] A near complete restoration of evoked field potentials can be achieved retroactively, but requires 240ug/mL to do so in vitro, thought to be due to direct antioxidant potential rather than induction of SOD.[42] Protective effects have also been noted in vitro in the range of 100-400mcg/mL Gypenosides against glutamate toxicity, thought to be secondary to an increase of γ-GCS and GR mRNA which attenuated glutathione depletion.[43]

May have protective effects secondary to inducing anti-oxidant enzymes, with both pretreatment and acute treatment being effective but a lower dose required if preloaded (possibly related to inducing anti-oxidant enzymes, rather than directly acting as an antioxidant)

In a model of rat cognitive impairment (BCCAO), rats injected with 100mg/kg or 200mg/kg Gynostemma Pentaphyllum for 61 days after surgery and assessed by a Morris water maze task (assessment of memory formation and retention) noted that only the higher dose was associated with improved memory formation following injury and was the only dose associated with improved Superoxide Dismutase (SOD), lipid peroxidation (MDA), and histological assessment.[44] Another study has induced BCCAO injury to rats but followed it up with oral ingestion of 200mg/kg or 400mg/kg concentrated Gypenoside (rather than the whole plant extract) for 33 days after injury and noted a somewhat attenuated adverse morphology on white matter of the brain associated with normalized SOD in the corpus callosum and optic tract with significantly attenuated 4-HNE and MDA.[45]

The particular Gypenoside known as TN-2 at doses of 10-40mg/kg was shown to inhibit scopolamine-induced learning deficits in the range of 40-96% with 20mg/kg being maximally effective.[46] There was no inhibitory effect on acetylcholinesterase (usually associated with improvements in scopolamine models), was equally effective as Tacrine as active control (10mg/kg) and was associated with an induction of CREB and BDNF in the hippocampus, the latter of which appeared to exceed the normal control group.[46] Similar protective effects have been noted with Gypenoside LXXIV.[14]

Protective effects have been noted at large concentrations of either oral or injected Gypenosides in animals, no human studies

4Cardiovascular Health

4.1Cardiac Tissue

Mechanistically, Gypenosides have once been shown to inhibit the Na(+),K(+)-ATPase enzyme in cardiac tissue in a reversible and concentration dependent manner between 10-300mcg/mL with an IC50 of 58.79+/-8.05mcg/mL (brain ATPase also inhibited with an IC50 of 52.07+/-6.25mcg/mL), and appeared to have less inhibitory potential when ATP concentrations were increased from 0.5mM to 5mM.[47] Gypenosides compete with sodium at the Na-binding site, causing a shift in ATP/Na-ATP equilibria and an increased affinity of ATPase for ATP, which overall established Gypenosides as counter competitors.[47] These effects may underlie how 2.5-10mg/kg (injections) of Gypensides (as well as injections of 0.7mg/kg Gypenoside III and 0.3mg/kg Gypenoside VIII) all exerted protection against toxin induced tachycardia and arrythmia; nearing the potency of Vermapril (1mg/kg) but slightly underperforming.[11] 

May preserve heart contractility to a moderate degree

In diabetic rats suffering from cardiomyopathy (streptozotocin injected), oral ingestion of 100mg/kg Gypenosides which was ineffective in reducing blood glucose over 6 weeks was able to normalize left ventricular function (LVSP, LVEPD) by about 41-55% (100% being that of control levels, 0% diabetic control) without significantly affecting titin or nebulin content, two cytoskeletal proteins of the heart.[48] This was hypothesized to be either through antioxidant effects of modulating calcium channels, although neither claim was tested.[48] 100mg/kg appears to be more effective than 50mg/kg and 200mg/kg, suggesting an optimal dosage range.[49]

Appears to reduce the adverse effects of high serum glucose on cardiac tissue in rats

4.2Nitric Oxide

Gypenosides from Southern Ginseng appears to induce endothelial-dependent vasorelaxation that is blocked by L-NAME, thus is mediated via the NO-cGMP pathway.[50] In cultured endothelial cells, incubation with 50mcg/mL mixed Gypenosides increased Nitric Oxide levels to 435+/-38.2% of control which was augmented with addition of the A23187 calcium ionophore and attenuated with Indomethacin.[50]

It is possible that Gypenosides may induce nitric oxide, but this was an in vitro study and not in a living system


Gypenosides at 300mcg/mL may decrease VCAM-1 mRNA activity, and a further ethanolic extract with a higher concentration of Gypenoside XLIX was able to decrease this activity (induced by TNF-α) at 50mcg/mL but with an IC50 of 186.8uM and near normalization to control cultures at 300mcg/mL.[15] This was hypothesized to be due to PPARα agonistic abilities[15] (with then inhibit NF-kB, a locus of whose inhibition greatly reduced VCAM-1) and this PPARα agonistic property has been previously noted, the potency of which is not significantly different than Wy-14643 at similar concentrations (trending to be weaker).[51][52] This was confirmed when MK-886 (PPARα inhibitor) abolished the benefits of this Gypenoside.[15]

May reduce vascular adhesion factors via PPARa, which may indirectly reduce atherosclerosis via preventing immune cell adhesion to the arterial wall


A study in obese rats given 150-250mg/kg Gynostemma Pentaphyllum (90% Gypenosides) for 5 weeks. At 4 days after ingestion triglycerides were unaltered at 150mg/kg while reduced 36% with 250mg/kg, 2 weeks in triglycerides were reduced 27% with 150mg/kg and 33%; the degree of triglyceride reduction appeared to max at around 35% at 5 weeks in both groups.[53] Total cholesterol was reduced in the range of 13-22% with a decrease in LDL-C as well (HDL-C unaffected).[53] 

There appeared to be improvements in postprandial triglycerides after 5 weeks of supplementation in response to a test meal with Gynostemma supplementation.[53] These hypolipidemic effects may also occur acutely, as one study using P407 (an inhibitor of lipoprotein lipase, which causes acute spikes in triglycerides) with a 4 day preload of Gypenosides at 250mg/kg was able to reduce the spike in triglycerides by 53% (total cholesterol by 10%, HDL unaffected) but more dramatic effects were noted after 14 days (85% attenuation of the P407-induced increase).[54] This was thought to be from attenuating the effects of P407 on the LPL enzyme, and Gypenosides in isolation had no effect on the LPL receptor between 5-100ug/mL.[54]

Appears to reduce circulating triglycerides over a prolonged period of time

A polysaccharide from Gynostemma appears to be able to bind to bile acids with a greater gram per gram affinity relative to psyllium fiber, which may underlie possible cholesterol reducing effects (currently unexplored).[55]

5Interactions with Fat Mass


200mg/kg of Actiponin (heat treated Southern Ginseng with 0.96% Damulin A and 0.68% Damulin B) over 8 weeks was able to attenuate weight gain of genetically obese mice by 8.1% relative to control; with the active control of 30mg/kg Sibutramine reducing this weight gain 10% independent of any changes in food intake.[23] A later portion of this study gave 150mg/kg and 300mg/kg to adult obese mice and noted a 5.7% and 7.7% reduction in body weight independent of food intake; these effects were thought to be mediated via AMPK activation in skeletal muscle tissue.[23]

Two compounds are suspected to be fat burners via AMPK activation and this has been noted in a living system, although the degree of benefit with a standard oral serving of Gynostemma Pentapyllum with a lower Damulin content is not known

6Interactions with Glucose Metabolism


Gynostemma Pentaphyllum (90% Gypenosides) appears to have an IC50 of 42.8µg/mL against α-glucoside (which outperformed Arcabose at 53.9µg/mL).[53]

May be able to reduce carbohydrate absorption; no fecal tests conducted so the degree of this inhibition is not known

Saponins in general from Gynostemma Pentaphyllum appears to have inhibitory potential on the PTP1B enzyme (a negative regulator of insulin signalling[56] that is a therapeutic target of Type II diabetes management[57]) in a concentration dependent manner, including gypensapogenin A (IC50 23uM), B (IC50 24.5uM), E (IC50 13.1uM), and G (IC50 19.7uM) with less efficacy (IC50 49uM) from F and some from 3β-hydroxyetio-17β-dammaranic acid (24.5uM)[8] with most potency coming from (20S)-3β,20,23ξ-Trihydroxydammarane-24-en-21-oic acid-21,23 lactone with an IC50 of 5.3+/-0.4μM via competitive inhibition with a Ki of 2.8μM; comparable to the active controls of corosolic acid (IC50 7.5+/-0.6μM) and ursolic acid (3.6+/-0.2μM).[58]

These compounds have been structurally modified (into compounds not naturally occurring in Southern Ginseng) to more potent inhibitors due to their novel structures; with IC50 values as low as 0.27uM.[59]

Compounds in Southern Ginseng appear to be relatively effective inhibitors of PTP1B, which can help glucose uptake into cells by preserving the function of the insulin receptor. At least in regards to natural options, these appear to be moderately potent

A compound from Gynostemma Pentaphyllum known as Phanoside appears to be able to induce insulin secretion[20] which can occur in both normal and diabetic pancreatic tissue at low and high normal glucose concentrations in a concentration-dependent manner.[19] Mechanistically, it was found to not be inhibited by any added agent at low glucose concentrations, which may be related to facilitating insulin exocytosis (as many classical mechanisms of K-ATP channel closure, calcium influx, and PKA/PKC activity were found to be independent of Phanoside).[19]

One compound may increase insulin secretion, which paired with a protective effect on the pancreas (see the Pancreas section of "Interactions with Organ Systems") Gypenosides may be pro-insulinogenic depending on context


When looking at rat studies, usage of 100mg/kg of the Gypenosides for 9 weeks fails to significantly reduce serum glucose in a streptozotocin-induced diabetic model.[48] Another study in db/db mice using low dose (0.0025% Gypenosides by weight of the diet) or high dose (0.01%) compared to rosiglitazone (0.005%) over 5 weeks noted that high dose was able to reduce fasting glucose (13.2%) but underperformed relative to rosiglitazone (57%); all test groups significantly increased fasting insulin levels relative to diabetic control.[60] Higher doses (200-300mg/kg injections; 1500mg/kg of oral ingestion) have been shown to acutely reduce blood glucose.[61]

In drug naive diabetics who were given gliclazide for 4 weeks at 30mg and then divided into group, 6g of Gynostemma Pentaphyllum (18% Saponins) in two divided doses against placebo (actually green tea catechins) noted that treatment with GP further decreased blood glucose and HbA1c although the improvement in insulin sensitivity was not statistically significant.[62] A tea made from Gynostemma Pentaphyllum (6g of the leaves) has been tested in isolation without drug therapy but alongside standard diet and exercise advice (also given to placebo tea group) in Type II Diabetics, and the Southern Ginseng group appeared to provide greater benefit to fasting glucose (5-fold greater reduction than placebo; totalling a 3+/-1.8mmol/L drop), HbA1c (2% reduction; placebo 0.2%), and insulin sensitivity over a period of 12 weeks.[63]

One rat study suggest high doses can acutely reduce glucose, but the two human studies conducted suggest that a tea made from Gynostemma Pentaphyllum can be an effective adjunct therapy alongside other treatments such as drug or exercise intervention and augment the efficacy of those interventions

7Skeletal Muscle and Performance


In myotubes, the two dammarane-type saponins known as Damulin A and B can activate AMPK in a concentration and time dependent manner and secondary to this increased glucose uptake 1.7-fold at 60ug/mL (of a solution containing 0.93% Damulin A and 0.68% Damulin B), increased GLUT4 mobilization and increased fatty acid oxidation (2.2-fold),[23] and the increase in beta-oxidation from 150uM Damulin A or 12uM Damulin B is comparable to 1mM AICAR and the glucose uptake of 150uM (but not 12uM Damulin B) was not significantly than different than 2mM Metformin (although trended to be less potent).[24] In feeding rats 150-300mg/kg of this mixture for 9 weeks, AMPK and ACC activity was enhanced in vivo in the soleus muscle.[23]

Appears to activate AMPK in skeletal muscle tissue, which has been noted to occur after oral administration to rats. This may underlie fat burning effects and perhaps some glucose/lipid reducing effects


One study administering a bioactive polysaccharide to mice named GPP1a was able to prolong exercise to fatigue and preserve glycogen content in exercised mice, which was associated with less oxidative markers (MDA);[34] this study is duplicated in Medline.[34]

Only one study in mice with an isolated polysaccharide shows promise; polysaccharide may not exist in non-caloric supplement capsules (although it should in tea, as it is water soluble)

8Inflammation and Immunology


In cultured mouse macrophages (J774A.1), mixed flavonoid extracts appear to have fairly weak suppressive effects on LPS-stimulated macrophages (when assessing cytokine release).[32] Similar suppressive effects are seen with the Gypenosides in RAW 264.7 macrophages where LPS-induced nitric oxide release is attenuated with an IC50 of 3.1+/-0.4ug/mL when pretreated before LPS, with 25mcg/mL being as potent as 10mcg/mL aminoguanidine; when added at a time similar to LPS induction, Gypenosides were weaker and reached maximal inhibition with 25mcg/mL at 47.3+/-0.1% (rather than absolute suppression seen with preincubation).[64] iNOS mRNA and protein content are reduced, and the mechanism is thought to be tied to NF-kB inhibition.[64]

Limited evidence, but Gypenosides and the flavonoids appear to be anti-inflammatory on immune cells

One polysaccharide (PSGP) has been noted to, following injections of 25-100mg/kg into mice and then having the macrophages removed after 8 hours, was able to induce macrophage activity with 100mg/kg being as effective as 0.2mg/kg LPS, and in vitro a concentration of 100mcg/mL being as effective as 0.2mg/mL LPS (with higher doses dose-dependently being more effective up to 400mcg/mL).[35]

A water soluble polysaccharide has been shown to be proinflammatory (immune booster)

Beyond the above mechanisms, Gynostemma Pentaphyllum may offer putative anti-oxidant protection in immune cells.[65]


A hot water extract of Gynostemma Pentaphyllum fed at either 1.75g/kg or 5g/kg bodyweight 5 days a week for 4 weeks noted that airway inflammation at both doses was not significantly different than control (all three groups significantly better than Ovalbumin control).[66] Similar effects have been noted within one week with 5g/kg, although in this study 1.75g/kg was ineffective.[67]

The increase in eosinophils in the lungs (+50% in Ovalbumin control) was significantly attenuated with both doses to a 16.18-22.54% with small dose dependence, with infiltration significantly reduced.[66]

Gynostemma Pentaphyllum can possibly be useful to prevent immune cell infiltration and hyperresponsiveness to allergins; would be useful to read the "Lung" section of "Interactions with Organ Systems" as Gynostemma may also be somewhat anti-asthmatic


10, 30, and 50mg/kg ethanolic extract of Southern Ginseng (for 7 days) prior to a 2 week stressor of electrical shocks has also noted that the stress reduced reduction in thymus and spleen weights were attenuated in a dose-dependent manner and Lymphocyte count somewhat preserved (48% preservation in the thymus, absolute preservation in the spleen with 50mg/kg only).[68] This study also noted preservation of TNF-α secretion in response to LPS, preservation of splenocytic proliferation, and T-cell cytotoxicity but IL-1β was seemingly unaffected.[68] Preservation of T-cell cytotoxicity and lymphocyte count as been noted with similar oral doses of Souther Ginseng in response to dexamethasone-induced immunosuppression in mice[69] and a preservation of lympocyte count has been noted against cadmium-induced lymphocyte decline.[70]

Appears to be able to attenuate immunosuppression induced by various agents (preventing the decline in immune cell count that would otherwise occur with stressors); an indirect immune support effect


Low dose injections of Gynostemma Pentaphyllum hot water extract can increase IgG2a[71] and T-cell proliferation in response to an antigen (in these studies, Concavalin-A) at 0.05-0.5mg/kg.[71][72]

In mice sensitized with Ovalbumin, administration of 1.75-5g/kg Gynostemma Pentaphyllum hot water extract for 4 weeks was able to attenuate the increase in IL-5 and TNF-α without affecting IL-6 or IL-13 alongside a decrease in antigen-specific IgG1 and IgE with no significant differences between groups; IFN-γ was not significantly affected.[66] This is noted within 7 days of 5g/kg treatment, but not 1.75g/kg[67] and usage of Gynostemma Pentaphyllum does not appeared to be associated with significant haemolytic activity when used as vaccine adjuvant where 200mcg Gypenosides induce more splenocyte proliferation than 200mcg Aluminum, but similar levels to that of 50-100mcg Quil-A (a saponin isolated from Quillaja saponaria with proven adjuvant properties).[73] This study noted that Gypenosides induced less IgG and IgG1 than Quil-A, but similar levels of IgG2b.[73]

Gypenosides may augment the body's antibody response to antigens, and act as an immune support agent. Limited evidence, however, but this effect is similar to that of Panax Ginseng

9Interactions with Organ Systems


Oral ingestion of 50, 100, or 200mg/kg Gynostemma Pentaphyllum given to mice alongside a testicular toxin (10mcg zearalenone) was able to wholly preserve superoxide dismutase (SOD) concentrations in the lowest dose relative to 10% alcohol control and progressively induced SOD activity in a dose-dependent manner; MDA (indicative of lipid peroxidation) was also reduced at all doses.[74] Germ cell apoptosis was greatly attenuated in a dose-dependent manner and this was associated with an increase in Bcl-2 to Bax (the higher the ratio indicative of cell survival), and histological examination appeared normalized at the highest dose.[74]

Appears to be quite protective of germ cells, which although isn't a 'pro-fertility' mechanism may indirectly support fertility. A fairly potent anti-oxidant effect in the testicles


One study using low-dose Gynostemma (0.005-0.05% of the rat diet) in db/db mice that developed diabetes noted that despite lacklustre effects on lowering glucose (dose was too low for this effect) that serum insulin was markedly higher than the diabetic control (75-224%) and higher than Rosiglitazone active control (29-139%).[60] As assessed by histological examination, Gynostemma at these doses appeared to greatly preserve the islets of Langerhans and the insulin-secreting β-cells that were perturbed during diabetic pathology.[60]

Low doses show have shown, in one study, to have fairly remarkable protective effects on the pancreas and preserve insulin secretion


One study noted that a saponin in Gynostemma Pentaphyllum is able to selectively activate LXRα, an enzyme highly localized to the liver that plays a role in cholesterol regulation.[75]

A study incubating hepatocytes with a high glucose and linoleic acid content (to mimic the conditions which damage liver cells during NAFLD[76][77]) found that an ethanolic extract of Gynostemma pentaphyllum was able to attenuate the concentration of triglycerides and cholesterol in hepatocytes in a concentration dependent manner between 100-300mcg/mL.[78] A reduction of F2-IsoPs was noted (although unreliable) and thought to be related to anti-oxidant properties; an increase of nitrate concentration was noted when coincubated with fatty acids only.[78]

Hepatic Stellate cell growth has been shown to be inhibited in vitro at 500μg/mL by Gypenosides via inhibiting the Akt/p70s6k pathway[79] and suppressing the secretions of the cytokines MCP-1 (40%), VEGF (17%), and TIMP-1 (25%) relative to untreated control;[80] this inhibition of MCP-1 also occurs with suppressed mRNA content, which is independent of the Akt/p70s6k pathway.[80] A reduction in type I procollagen also occured in a dose-dependent manner, although on all markers concentrations of 100-400mcg/mL were much less effective than 500mcg/mL.[80] These mechanisms may underlie the anti-fibrotic effect observed in vivo, when rats given Gynostemma Pentaphyllum experienced less collagen growth in their livers in response to a fibrosis-inducing toxin (CCl4).[81]

General protective effects from mixed anti-oxidant and anti-inflammatory mechanisms, may be anti-fibrotic and protect liver cells during instances of NAFLD

In rats given a high fat and cholesterol diet with some alcohol (to induce hepatic steatotosis) Gypenosides given at 15, 30, or 60mg/kg noted that the high dose group was approximately as effective as Silymarin at 23mg/kg in attenuating weight gain over 10 weeks and attenuating the hepatic index, but was more effective at reducing intrahepatic triglycerides (although PPARα mRNA levels were similar between groups; both higher than control).[82] ALT and AST were reduced similarly in the 30-60mg/kg Gypenoside groups as was the Silymarin group.[82]

One pilot study that compared 80mL Gynostemma Pentaphyllumtea against placebo in persons with Non-Alcoholic Fatty Liver (NAFLD) in conjunction with dieting noted that while diet was effective at all time points, the addition of tea failed to exert any significant benefit at 2 months but at 6 months was associated with significantly improved insulin sensitivity, weight loss, and serum liver enzyme profile relative to dieting placebo.[83]

In instances of high liver fat (NAFLD), Gynostemma Pentaphyllum has shown benefit following oral administration; only one human study using low dose tea but showed benefit over 6 months


Gypenosides may have protective effects against renal fibrosis via attenuating changes in TGF-ß1, CTGF, and Smad7 (proteins involved in pathogenesis of fibrosis)[84] and a single dose of 200mg/kg oral Gypenosides has shown to reverse the increase in urinary protein excretion induced by 10mg/kg Indomethacin, trending (nonsignificantly) to be less than control rats.[85] An increase in urinary N-acetyl-β-glucosaminidase was noted with the paired group (usually indicative of tubular toxicity), but there was no group taking Gypenosides in isolation to assess whether this is a per se effect of Gypenosides.[85]

Protective effects against fibrosis may also apply to the kidney, and although one study noted a normalization of urinary protein (indicative of renal protection) some biomarkers were not ideal; further research is needed

9.5Digestive Tract

When 200mg/kg Gypenosides is taken 30 minutes prior to an overdose of NSAIDs (10mg/kg Indomethacin), the Gypenosides exert good protection of NSAID-induced ulcer inductions as assessed by ulceration area (mm3); reducing the ulcer by approximately 91%.[85] Similar protective effects are observed in the intestines where ulceration was reduced by 88% and increases in haptoglobin (serum) and haemoglobin (caecal) with Indomethacin were effectively normalized.[85] Protection against Helibactor Pylori induced ulcers,[86]stress-induced ulcers, and acid with alcohol induced ulcers.[87]

Appears to be quite an anti-ulcer agent in repeated animal studies against a variety of ulcer inducing agents

In a study on Indomethacin-induced toxicity, it was found that while intervention with Indomethacin did not alter intestinal microflora that Gypenosides at 200mg/kg (with Indomethacin, no Gypenoside-only group) was associated with a decrease in lactose-fermenting bacteria from 88-89.7% of bacteria to 25%; this was accompanied by an increase in bacteria per gram of tissue by 7.3-fold (Indomethacin) and 18-fold (Gynostemma and Indomethacin).[85]

May interaction with gut microflora, practical significance unknown and the study not adequately designed to assess the impact of Gynostemma Pentaphyllum per se


One study in Guinea pigs noted that while injections of 2.5-10mg/kg Gypenosides (or alternatively, 0.7mg/kg Gypenoside III and 0.3mg/kg Gypenoside VIII) caused a slight decrease in pulmonary ventilation pressure and resistance at the highest dose, all doses were effective in reducing histamine-induced constriction to a degree (66-68% inhibition with Gypenosides, no dose dependence noted).[88] In response to an antigen (which induces bronchoconstriction), 10mg/kg Gypenosides caused 80% inhibition of constriction which was similar to the active control of 10mg/kg Sodium Cromoglicate.[88]

May have anti-histamine mechanisms and preserve an 'open airway' through inhibiting constriction, without per se causing dilation

10Interactions with Cancer


An extract of Gypenosides at 60-180ug/mL in SAS oral cancer cells is able to increase cell count in the G0/G1 and subGo/G1 phases and decreased S phase count; this was secondary to a calcium and ROS-dependent induction of apoptosis in a time and concentration dependent manner with 180ug/mL for 72 hours causing near absolute apoptosis via mitochondrial caspase release[89][90] and possibly by inhibiting DNA repair in SAS cells.[91] Cytochrome C and Endo-G have been noted to be released from the mitochondria (indicative of disturbed membrane potential) and GADD153 induction and nuclear translocation has been noted to be dependent on catalase (and thought to be related to ER stress).[92]

Gypenosides may also have anti-proliferative effects in this same cell line (SAS) as 90-180mcg/mL Gypenosides for 24-48h in vitro noted that while 90mcg/mL greatly attenuated migration, 180mcg/mL at both time points abolished migration.[90] Using a Matrigel assay, 90mcg/mL reduced migration (32-46%) and invasion (28-65%) while 180mcg/mL further reduced migration (63-78%) and invasion (51-80%) in a time dependent manner.[90] This was thought the be related to suppression of MMP proteins (2, 7, 9) and NF-kB.[90][93]

In mice injected with SAS cells to induce a tumor, injections of 20mg/kg Gypenosides for 28 days decreased tumor weight by 34% while the active control group (2mg/kg Doxorubicin) halved tumor size.[89]

Appears to have repeated in vitro evidence, and one mouse study suggesting it can be useful to reduce the size of oral cancer cell tumors; it underperformed relative to the reference drug Doxorubicin


In a HL-60 myeloid leukemia cells, gypenosides were shown to induce time and concentration dependent reductions in cell viability with 200ug/mL reducing survival to less than 20%. These changes were associated with an increase in G0/G1 cell count and a decrease in S phase, thought to be through a decrease in mitochondrial permeability and an increase in caspase release associated with an increase in intracellular calcium and ROS.[94] Another test in WEHI-3 (myelomonocytic leukemia macrophage-like) leukemia cells also noted DNA damage induced by Gypenosides reaching sub 40% viability after 48 hours of 200ug/mL and sub 20% after 72 hours of 150ug/mL, associated with the same cell phase changes and pro-oxidative mitochondrial pathway.[95]

In mice given injections of HL-60 (to induce tumor formation) given either 5 or 20mg/kg injections of Gypenosides every third day for a period of 4 weeks tumor size was reduced 56% with the higher dose with 5mg/kg not being significantly different than control.[94] Another study with daily injections of 2-4mg/kg total Gypenosides after injection with WEHI-3 leukemia cells noted dose-dependent prolongation of survival time (from 40% to 70% over 2 weeks),increases in megakaryocytes and CD3/CD19 cells, and a decrease in spleen weight.[95]

Possible anti-leukemic effects which have been noted twice in mice injected with leukemic cells; no comparison to a reference drug to assess potency, however


A screening study in Hep3B cells to assess bioactives that can induce apoptosis or halt proliferation of this cell line noted that the saponin fragment could reduce proliferation to 22.4% at 100ug/mL and the flavonoid fragment to 14.6% at 100ug/mL (IC50 47.6ug/mL and 57.8ug/mL respectively).[13] In Huh-7 cells, Gypenosides appear to induce apoptosis by a ROS and Calcium-mediated increase in mitochondrial membrane permeability which induces caspase release[96] and similar apoptotic results to these two cell lines (Hep3B and Huh7) have been seen in HA22T cells.[97][98]

Appears to induce cell death in a variety of liver cancer cells, no in vivo evidence


In a preliminary study A549 lung cancer cells, the molecule gypensapogenin C appears to induce cytotoxicity at an IC50 of 0.11+/-0.3μM.[2] In general, mixed Gypenosides can induce concentration and time dependent apoptosis in A549 cells associated with cell accumulation in G0/G1 and sub-G1 phases and DNA fragmentation and caspase release.[99]

General cell killing effect in lung cells; practical significance unknown


Gypensapogenin C appears to induce cytotoxicity in U87 glioblastoma cells with an IC50 of 0.58 ± 0.16μM.[2]

A study assessing C6 glioma tumor cells, 24-240mcg/mL (ethanolic extract) acutely reduced H2O2 levels in a concentration dependent manner with an induction of SOD up to 2-fold over 48 hours of incubation at 120mcg/mL or above;[100] this surprisingly occurred with a concentration and time dependent decrease in cell viability in tumor cells associated with caspase-3 release (almost abolishing proliferation at 72 hours with 240mcg/mL) and did not seem to influence non-cancerous astrocytes within the tested dose range.[100]

Standard cell killing effects in glioma cells, with at least one study noting that healthy cells were not affect at this concentration; no living models have been tested yet


Using a saponin-rich fraction of Gynostemma pentaphyllum, a weak inhibition of proliferation (12.1%) was noted with 10ug/mL increasing to over 80% at 100ug/mL with slightly more effective inhibition at graded concentration of a flavonoid rich extract up to 150ug/mL; the IC50 values were 33.3μg/mL and 39.3μg/mL respectively.[29] These effects were accompanied by an increase in sub-G0/G1 and decrease in G0/G1 phase and related to the mitochondrial-caspase pathway.[29]

Possible anti-prostate cancer effects, practical significance unknown and not overly potent either


Gypenosides appears to reduce NAT1 protein and mRNA content in a dose-dependent manner, which has been associated with less DNA adduct formation in HeLa cells incubated with 2-aminofluorene (which binds to DNA after being acetylated by NAT1 enzymes).[101][102]

Practical significance of oral supplementation unknown


Gypenosides are able to cause apoptosis in Colo205 cells in a concentration and time dependent manner with an IC50 of 113.5ug/mL, which is related to mitochondrial caspase release from ROS and calcium; an increaes in G0/G1 and subG1 phases are seen in this cell line.[103] This study also noted increase levels of p15, p16, p21, p27, and p53, and the authors hypothesized the mechanism of action was related to inducing p53 (which would positively influence p21 and p27, and the increase in Bax would mediate apoptosis).[103]

Possible anti-cancer effects, with moderate to weak potency (judging by the IC50 values) and no living system tested

11Nutrient-Nutrient Interactions


SK0506 is a herbal mixture of Coptis Chinensis (source of Berberine), Salvia miltiorrhiza, and Gynostemma Pentaphyllum; used for the treatment of diabetes. A rat study using 1000mg Gypenosides, 800mg Berberine, and 500mg Tanshinone IIA per kg bodyweight in rats with metabolic syndrome for 4 weeks noted that rats fed SK0506 was able to reduce plasma triglycerides (34%), NEFA (22%), and cholesterol (31%) with some ability to reduce insulin (37%); in comparison to the active control of 3mg/kg Rosiglitazone, SK0506 outperformed on lipid parameters and underperformed for reducing insulin and improving insulin sensitivity while both failed at reducing glucose significantly over 4 weeks. When measuring body weight, the SK0506 group experienced a decrease in fat mass and body weight while the active control Rosiglitazone expectedly increased body weight.[104]

Possible synergism among these compounds for the purpose of being anti-diabetic, although delineation between the active components has not been done yet

11.2Grape Seed Extract

Grape Seed Extract (GSE; essentially a source of Procyanidin compounds) has been tested alongside Gypenosides at 40mg/kg each supplement (against other groups of 80mg/kg GSE, 80mg/kg Gypenosides, and 500mg/kg Metformin as active controls) in mice on a high fat paired with fructose diet that suffered from hepatic insulin resistance (due to diet composition) over a period of 6 weeks.[105]

This study noted that the combination therapy group outperformed both isolated Gypenosides and isolated GSE in reducing the percent body fat gained slightly which was not significantly different than control and normalized serum glucose, insulin, and insulin sensitivity; combination therapy was equally effective as Metformin at reducing serum insulin while being slightly (but significantly) more effective at reducing serum glucose and improving insulin sensitivity.[105] Combination therapy, but not either treatment in isolation, was equally effective as Metformin in response to an oral glucose tolerance test.[105]

One study in rats suggest that Grape Seed Extract and Gypenosides are highly synergistic in improving central insulin resistance, and combination therapy rivalling the efficacy of Metformin

12Safety and Toxicity


Oral doses up to 750mg/kg of Gynostemma Pentaphyllum water extract failed to exert any appreciable toxic effects in rats over a period of 6 months aside from a slight but nonsignificant reduction in weight, seen in a dose-dependent manner.[106] No differences were observed in food intake or behaviour, organ weight, or hematological parameters.[106] A rough estimate for the equivalent human dose of 750mg/kg in rats is 120mg/kg water extract in humans,[107] or 8g daily for a 150lb person. Oral doses of up to 400mg Gynostemma Pentaphyllum for 2 months has been shown to be safe in otherwise healthy humans.[1]

No toxicity has been reported with moderate to high usage of Gynostemma, although evidence is limited


A hot water extract of Gynostemma Pentaphyllum failed to exert mutagenicity (induce mutations) to Salmonella typhimurium, TA 98, and TA 100 with or without metabolic activity.[108] When testing coincubation with known carcinogens, Gynostemma hot water extract protected against 7 including Benzo(a)pyrine induced mutagenesis (a carcinogen found in cooked meat) although it augmented mutagenicity from the two test compounds 2-AA (TA98 strain) and MNNG (TA100 strain) with decreasing augmentation as the concentration increased.[108]

Gynostemma has been reported to induce DT-diaphorase activity in murine hepatoma cells in a concentration dependent manner,[108] which is a mechanism associated with protection from carcinogens.[109]

Mixed effects on genomic damage, although for the most part it appears to protect the genome from damage


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