Jiaogulan

A paradox lies at the heart of jiaogulan, in that it is both bitter and sweet, draining and nourishing, which makes it capable of removing stagnation while simultaneously restoring deficiencies. Its affinity for the Lungs and Spleen implies that it can enhance our acquired energy systems, clearing obstructions of the airways and helping digestion, while also increasing our physical endurance.

Meanwhile, its affinity for the Kidneys and Heart suggests it can also improve our innate energy, regulating the essential water–fire axis that drives the basic dynamic of life (16). Here too it clears obstructions that upset this balance, while also providing a boost to these systems when weak making it an invaluable herb for cardiovascular and metabolic diseases. This uniquely balanced profile makes it one of the few Chinese herbs that is most often taken alone, as a substitute for green tea, rather than worked into formulas.

Its cooling nature imposes some limits on these activities, making it better for clearing hot conditions and for nourishing fluids. This means that it treats mainly thick phlegm obstructing the lungs and conditions of excess digestive heat such as stomach ulcers, as well as reducing accumulations that affect the Heart (the Fire organ) leading to obstructed circulation, or disturbances to the Spirit that cause mental agitation. It is not the herb of choice for cold-excess patterns, such as watery sputum in the lungs, chills and spasmodic cramps.

Similarly, it also tends to be better at generating fluids to moisten dry lungs or treating erosive gastric conditions, and less applicable for warming the innate “Life Gate Fire,” or improving the digestive functions of the Spleen that depend upon warmth and dryness. In these cold-deficiency patterns, it may be used as part of a coordinated strategy but should not be relied upon alone.

Jiaogulan performs a delicate balancing act, clearing without weakening and nourishing without stagnation. This makes it well suited for prolonged use, to treat the low grade heat that slowly damages the yin and fluids, that then erode or accumulate in a pathological form. This is characteristic of many chronic diseases, and even of ageing itself (17), hence, its common name, “the herb of immortality.” (1)

Cardiovascular system

The primary use of G. pentaphyllum in cardiovascular diseases is for managing dyslipidemia. A systematic review of 22 randomized controlled trials found that gypenosides, the herb’s active saponins, demonstrate comparable effects to standard lipid-lowering agents on total cholesterol, triglycerides, and HDL-cholesterol levels, with fewer adverse events (24). The herb appears especially beneficial as an adjunctive therapy; with superior effects on triglycerides, LDL-cholesterol, and HDL-cholesterol obtained by combining it with lipid-lowering agents than with either treatment alone.

Mechanistic studies reveal that the gypenoside constituents lower hepatic cholesterol through multiple pathways, by inhibiting endogenous cholesterol synthesis by downregulating key enzymes (Hmgcs1, Fdft1, Pmvk, Mvd), promoting cholesterol efflux via upregulation of Abca1 and ApoB, and accelerating steroid hormone metabolism (25).

The cardioprotective effects of G. pentaphyllum extend beyond lipid regulation, with gypenosides being shown to preserve mitochondrial function in cardiomyocytes, restore cellular ATP content, and improve mitochondrial membrane potential through activation of the PI3K/Akt/GSK-3β/Mcl-1 signaling pathway (26). This helps to improve cellular survival and energy production in cardiomyocytes threatened by a number of diseases including myocardial infarction, ischemia-reperfusion injury, diabetic cardiomyopathy, atherosclerosis and doxorubicin induced heart injury.

Digestive system

One of the traditional uses of G. pentaphyllum is for chronic gastric and duodenal ulcers (4), although clinical data specific to digestive conditions remains limited to a single study that indicated its action was to preserve the gastric wall mucus, and not related to gastric volume, pH increase, or acidity output (27). Its polysaccharide components are recognised for their protective effect against gastric cancers and hepatic injury (28) and can reverse serum transaminase elevations induced by statins (24).

Endocrine system

G. pentaphyllum demonstrates significant potential for metabolic health, particularly in type 2 diabetes management. In animal studies, Gynostemma extract (0.3 g/kg daily for two weeks) significantly improved glucose tolerance in diabetic Goto-Kakizaki rats, with treated animals showing markedly lower blood glucose levels at 120 minutes post-glucose challenge (29). Plasma insulin levels increased by 1.9-fold compared to controls, and isolated islets from treated rats showed enhanced insulin secretion at high glucose concentrations.

Mechanistically, gypenosides stimulate insulin release via ATP-sensitive potassium channels, L-type calcium channels, and the PKA signaling system, with effects dependent on pertussis toxin-sensitive Ge-proteins. Another study identified a modulating effect on the IRS1/PI3K/Akt signaling pathway, promoting glycogen synthesis and inhibiting gluconeogenesis (30). Its simultaneous activities on lowering cholesterol and blood glucose have made it a valuable consideration for metabolic syndromes and diabetic patients with concurrent dyslipidemia, outperforming lovastatin in this respect (24).

Immune system

Polysaccharides and gypenosides from G. pentaphyllum are well recognised for their ability to modulate immunity, affecting both innate and adaptive immune responses through multiple mechanisms, underpinning its traditional actions of clearing heat, resolving toxicity and supplementing deficiency (4).

In enhancing immunity, the polysaccharide content is recognised as one of the key components (28). Studies in immunosuppressed mice showed significant increases in spleen and thymus indices, activation of macrophage phagocytosis and NK cell activity, and elevated CD4+ T lymphocyte counts as well as the CD4+/CD8+ ratio in a dose-dependent manner (31). Other studies have revealed that gypenosides activate the antitumor immunity of CD8+ T cells against melanoma (32) and enhance the immune response against hepatocellular carcinoma (33).

Conversely, other studies have revealed anti-inflammatory activities associated with gypenosides extracted from G. pentaphyllum. In macrophage cell models, the extract significantly reduced nitric oxide production and decreased expression of cyclooxygenase-2, prostaglandin E2, and the pro-inflammatory cytokine TNF-α in a dose-dependent manner (34). Gypenoside XVII has also been observed to promote macrophage polarization toward the M2 (anti-inflammatory) phenotype while inhibiting M1-associated pro-inflammatory responses (35).

One particular area of interest is the reduction of pro-inflammatory cytokines involved in neuroinflammation. One study found interleukin 1β being reduced by approximately 70% in hippocampal tissue and 44% in prefrontal cortex tissue in experimental models by suppressing NLRP3 inflammasome activation, a key mediator of inflammatory responses, and modulation glial cell activation and phenotypic polarization (36). Network analyses revealed 13 G. pentaphyllum compounds had 18 intersecting targets with Alzheimer’s disease, with the primary targets being epidermal growth factor receptor, IL-1β, IL-6, nitric oxide synthase in endothelial and serum paraoxonase/arylesterase 1 (37).

Respiratory system

Traditionally, jiaogulan has been primarily used for respiratory conditions, with the ability to expel phlegm and generate fluids, giving it a great versatility in both dry and productive coughs, although its cold nature suggests it is better suited for hot conditions with thick phlegm, sore throat and fever predominating over chills (4). Preclinical studies support this action with intravenous administration of 2.5–10 mg/kg aqueous extract into sensitised guinea pigs decreasing bronchial resistance under basal conditions, reducing histamine-induced bronchoconstriction by 68% and antagonising antigen-induced bronchoconstriction by 80% (38).

Gypenosides have also revealed anti-inflammatory effects through inhibition of the AKT/mTOR/c-Myc pathway which reduced the mortality of bleomycin-induced pulmonary fibrosis mice from 40% in the control group to 0% in the treatment group (39).

G. pentaphyllum has also been researched in relation to Covid-19. Network analysis revealed 59 active compounds from the herb, with 19 targets overlapping with Covid-19-associated genes, with its flavonoid and saponin profiles having distinct but interconnecting axes central to the disease (40). The flavonoid component targeted pro-inflammatory genes including interleukin 1B, interleukin 6, tumour necrosis factor, and nitric oxide synthase 2 which drive the cytokine storm responsible for acute respiratory distress syndrome.

Gypenoside LI demonstrated strong binding to angiotensin converting enzyme (ACE, the primary receptor for SARS-CoV-2) and renin, suggesting potential to interfere with viral entry and regulate vascular homeostasis, mechanisms that link cardiovascular health to Covid-19 severity. In addition, the simultaneous use of G. pentaphyllum in respiratory, cardiovascular and metabolic disorders and its reputation for enhancing longevity also make it an interesting herb for future research due to age and pre-existing metabolic comorbidities exacerbating the risk of respiratory failure in Covid-19 (41).

Gynostemma pentaphyllum increases exercise performance and alters mitochondrial respiration and AMPK in healthy males

Nayyar et al. (42) conducted a double-blind randomised crossover placebo control trial in human participants to measure the effects of G. pentaphyllum on exercise performance, AMP-activated protein kinase (AMPK), and mitochondrial signaling in human muscle. Sixteen healthy untrained healthy males between 18–35 years old were given either placebo or 450 mg of G. pentaphyllum dried leaf extract equivalent to 2.25 g of dry leaf per day for four weeks. Extracts contained 20(S)-ginsenoside Rg3 (0.24%); gypenoside (2.14%) and marker saponin (1.63%).

Improvements in exercise performance were measured with steady-state and time to exhaustion tests and a 20 km time trial, while mitochondrial analysis was performed through muscle biopsy of the vastus lateralis muscle taken at rest (0 min), at the midpoint (30 min), and at the conclusion of the 60 min steady-state submaximal exercise bout and analysed for gene and protein expression, electron transport system respiration and oxidative phosphorylation. Blood was also collected and examined for cholesterol, leptin and adiponectin.

The results showed no change in body weight or power output but improved performance in the 20 km time trial by approximately 4%. Plasma glucose, leptin and acetyl-CoA carboxylase (ACC) concentrations were lower and HDL cholesterol levels were higher following four weeks of G. pentaphyllum supplementation. The active arm also experienced a higher resting oxygen flux per mass of fresh muscle at complex I and a reduction in maximal oxidative phosphorylation capacity following exercise when compared to placebo.

There was also a significant increase in AMPK Thr172 phosphorylation levels after 60 min exercise in the supplemented group, which was not observed in the placebo group. Combined these suggest an increase in mitochondrial respiratory function, mediated by alterations in AMP and ACC, resulting in lower plasma leptin and glucose levels.

This study added to the existing research into the use of G. pentaphyllum in metabolic conditions by studying the changes in mitochondrial respiration in skeletal muscle tissue following supplementation, and suggesting this to be a possible mechanism of action.

It is one of the few studies to look at in vivo changes in mitochondrial function in human participants following herbal supplementation, but is limited by its small number of participants, short intervention period, lack of adverse event reporting and the use of a single gender with no health conditions. It does lay the groundwork for future studies that can use more arms of different dosages, look at different kinds of exercise, and research the effects on people with metabolic disorders.

The effect of an orally‐dosed Gynostemma pentaphyllum extract (ActivAMP®) on body composition in overweight, adult men and women: A double‐blind, randomised, placebo‐controlled study

Rao et al. (43) examined the effect of a G. pentaphyllum extract on improving body composition in 117 overweight Australian men and women in a double‐blind, randomised, clinical trial. Participants were over 18 and had a BMI between 25 and 35. The active arm received a commercial brand of encapsulated G. pentaphyllum from Korea (ActivAMP®) standardised to 450 mg extract per day, for 16 weeks, while the placebo arm received a capsule of maltodextrin.

Effects were measured primarily through body composition with dual‐energy X‐ray absorptiometry to measure total body fat and fat‐free mass. Secondary anthropometry measures of height, weight, hip and waist circumference, along with blood samples, dietary intake diaries and quality of life questionnaires were also taken.

The results demonstrated that 16 weeks of G. pentaphyllum supplementation resulted in a significant reduction in total body weight, fat mass and BMI compared to the placebo group. Subgroup analysis revealed that males had a significant reduction in visceral fat (abdominal), whereas females had a significant reduction in gynoid fat (hips and thighs), compared to the placebo group.

However, there was no reduction in waist or hip circumference between groups. Other significant outcomes included a reduction in tumour necrosis factor-α, which was initially raised in both groups but returned almost baseline in the supplemented group, indicating a reduction in inflammation associated with adipose tissue. The extracts were well tolerated with five reported adverse events in the treatment group (diarrhoea, insomnia, dizziness, nausea, dry throat), compared to two in the placebo group (fatigue, increased bowel movements).

This study revealed the potential for G. pentaphyllum to play a role in the health conditions associated with obesity and visceral fat, which are some of the leading causes of death today. It was limited by a relatively small sample size that would need to be repeated in a larger population, and not measuring AMPK signalling, despite mentioning it as the most likely mechanism. The authors conclude that G. pentaphyllum could be an important addition to diet and exercise interventions for the treatment of metabolic conditions such as non-alcoholic fatty liver disease, insulin resistance and obesity.

Effects of gypenoside L-containing Gynostemma pentaphyllum extract on fatigue and physical performance: A double-blind, placebo-controlled, randomized trial

Ahn et al. (5) conducted a randomized, double-blind, placebo-controlled study to evaluate the effect of gypenoside L in G. pentaphyllum extract under non-exercise conditions on the improvement of physical performance. Participants were 100 healthy adults aged 19–60 years who agreed to an exercise stress test, randomly assigned to either the control or treatment group. Treatment consisted of a capsule with G. pentaphyllum extract, standardised to ensure it contained 18.46 ± 0.13 mg/g of gypenoside L and 1.61 ± 0.01 mg/g ginsenoside Rg3. The placebo group received a 700 mg capsule containing cyclodextrin, magnesium stearate, and silicon dioxide. All participants consumed a capsule once daily for 12 weeks.

Physiological assessments were measured at baseline and after 12 weeks of treatment. BMI was calculated from height and weight. Blood pressure and pulse were measured pre-exercise, post-exercise, and after recovery. Post-exercise cardiorespiratory responses, biochemical parameters of fatigue, and exercise responses were measured and compared at baseline and 12 weeks. The Global Physical Activity Questionnaire assessed their metabolic equivalent of task.

Cardiopulmonary responses, specifically VO₂ peak, O₂ pulse, and maximal heart rate (HRmax) were measured on a motorized treadmill using a modified Bruce protocol. Exhaustion was assessed using the ratings of perceived exertion scale, visual analog scale (VAS), and multidimensional fatigue scale were used to assess exercise response. Biochemical markers of fatigue, such as serum levels of myoglobin, interleukin-6, total antioxidant status, and endothelial nitric oxide synthase were examined.

The significant results found were that post-exercise levels of lactic acid, ammonia, lactate dehydrogenase, and free fatty acid in the blood serum were higher after 12 weeks of treatment than at baseline, the VO₂ max value was higher in the treatment group after 12 weeks of treatment than at baseline, VO₂ max was significantly different between the two groups, and temporal fatigue was significantly lower in the treatment group than in the control group, while no significant changes in the multidimensional fatigue scale were noted in the control group.

This showed 12 weeks of supplementation with G. pentaphyllum extract improved blood parameters in the recovery period compared to baseline, and induced positive changes in cardiopulmonary and exercise responses and endothelial nitric oxide synthase levels compared with the control, suggesting improved physical and mental performance. Although the study focused on the presence of gypenoside L in the extract, up to 1108 saponins have been isolated and characterised (44) from G. pentaphyllum meaning these effects could be due to any number of other constituents.

Supplementation with extract of Gynostemma pentaphyllum leaves reduces anxiety in healthy subjects with chronic psychological stress: A randomized, double-blind, placebo-controlled clinical trial

Choi et al. (6) tried to investigate the effect of jiaogulan on anxiety from chronic psychological stress by recruiting 72 healthy adults who had perceived chronic stress and anxiety with a score on the State-Trait Anxiety Inventory (STAI) from 40 to 60. 36 received 200 mg of G. pentaphyllum extract, while the other 36 received placebo for 8 weeks and were exposed to repetitive loads of stress by performing a serial subtraction task for 5 min every second day.

Primary outcomes were measured using changes in anxiety on the Trait-STAI, while secondary outcomes were State-STAI, total score of STAI, Hamilton Anxiety Inventory (HAM-A) and Beck Anxiety Inventory (BAI). Further biomarkers of stress were also taken, including blood noradrenaline and adrenocorticotropic hormone (ACTH), salivary cortisol and alpha-amylase, cardiovascular autonomic nervous system (ANS) functional test, and heart rate variability (HRV) test, measured before and after the intervention.

The Trait-STAI decreased in the active arm by 16.8% compared to the placebo (p = 0.041), but there were no other significant differences in any of the other parameters. Both groups saw reductions in all the psychometric tests which may be predictable since psychological states are likely to respond to the non-specific effects of the psychological component of the interventions.

There was also no causal relationship between consumption of the herb and any adverse effects. This suggests that G. pentaphyllum supplementation may reduce anxiety proneness in subjects under chronic stress, but that this effect is only specific to G. pentaphyllum in this one particular parameter.

Therapeutic potential of Gynostemma pentaphyllum extract for hair health enhancement: A randomized, double-blind, placebo-controlled clinical trial

Following its reputation as a “herb of immortality,” (1) Lee et al. (45) evaluated the efficacy and safety of G. pentaphyllum extract in improving general hair health parameters in adults with moderately damaged hair. They recruited 100 healthy adults aged 19–60 years with moderately damaged hair, determined by visual assessment and a hair damage score, into a randomized, double-blind, placebo-controlled trial.

Participants were randomly allocated to receive either 340 mL/day of G. pentaphyllum extract or a placebo for 24 weeks, to be consumed internally. Primary outcomes were changes in objective hair parameters, including elasticity, density and diameter, as well as subjective satisfaction. Secondary outcomes included safety evaluation, monitoring for adverse events, laboratory tests and hair glossiness.

After 24 weeks, the active group showed significantly greater hair elasticity, a threefold increase in density and a fourfold increase in hair diameter. The G. pentaphyllum group also self-reported greater satisfaction scores with better outcomes in reducing hair damage and dryness that corroborated the objective findings.

Among the secondary measures, no significant differences in hair glossiness were observed between the two groups, and there were no severe adverse events reported, indicating an excellent safety profile. The authors conclude that G. pentaphyllum extract is a promising natural therapeutic agent for enhancing hair health, offering significant functional improvements with a favorable safety profile.

Its main traditional function is to strengthen the body and generate fluids, especially by moistening the lungs and helping to dispel phlegm that is often the result of chronic impaired fluid metabolism (4). This makes it most applicable for asthma, chronic bronchitis and similar disorders of impaired respiratory and gastrointestinal functioning. It can also be used in the treatment of chronic neurological disorders like migraines and neuralgia which often involve a level of deficiency. This nourishing and moistening property is reflected in some sources ascribing it a sweet taste (18), while others do not (4).

Its second traditional use is for clearing heat and eliminating toxicity to reduce swelling, inflammation and pain (4). It is particularly useful for gastric and duodenal ulcers, nodules, tumours and cystitis, where it is consumed internally, or applied topically to herpes zoster and liver spots. This is perhaps its oldest medicinal use, reflected in Li Shizhen’s description, and deriving from its cold and bitter taste that all sources agree on.

Recently, jiaogulan has also been used for supporting cardiovascular health by lowering blood pressure and cholesterol (4). This has meant that some sources indicate that this herb enters the Heart meridian while others rely on its historical indications and do not (18). Furthermore, recent research indicates it may also treat anxiety (19) which is not described in traditional manuals, but would be an obvious extension to its cooling, phlegm clearing properties and affinity for the Heart meridian.

Another modern indication that has attracted much attention is its use in metabolic disorders. This is also based on modern research which has seen positive results in trials investigating obesity (20), exercise performance (21) and fatigue (5), with suggestions it could treat metabolic disorders such as non-alcoholic fatty liver disease and insulin resistance. While this also does not appear in traditional manuals, it can be explained by its traditional actions. Zhu Danxi noted that individuals with a higher body weight “have more phlegm and dampness,” while Zhang Jingyue said that they “have more qi deficiency, more dampness, and more stagnation” (22).

Meanwhile, the traditional concept of diabetes (xiao ke) stems from internal heat that causes an excessive thirst, appetite and urination that results in a wasting disorder (23). This means that a herb which fortifies the Spleen and Lungs to improve fluid metabolism and movement, dispels chronic phlegm and clears heat while moistening dryness to alleviate thirst is an ideal choice for metabolic disorders from a traditional perspective.

Since the discovery of ginsenosides found within G. pentaphyllum, the only example outside of the true ginseng family (Araliaceae) (2,3), its uses have expanded considerably beyond its traditional indications for stubborn chest phlegm, digestive disorders and inflammation (4). This has given it many of the adaptogenic applications of ginseng including for the relief of stress, including physical and mental fatigue, stress-related anxiety, heart disease prevention of food hypersensitivity through modulation of intestinal flora and the prevention of cancer (5–9).

The property that has attracted the most interest today is in the ability of G. pentaphyllum saponins to regulate metabolism. This has made it of particular interest in the treatment of many disorders common today such as diabetes, obesity, non-alcoholic liver disease and atherosclerosis (10). Its protective activity on the heart also makes it especially useful for reducing blood markers that predispose people to diseases such as high cholesterol, blood sugar and pressure. In these areas it has traditionally been drunk as a tea, but it has been suggested that its individual saponins could be useful as a sweetener and food additive to bring its protective effects to a wider audience (11).

Another use that has become popular today is as an anti-ageing supplement. Its impressive adatogenic properties were discovered in the 1970s after a census revealed that people living in the particular mountain region where this herb was regularly drunk as tea had a surprising number of centenarians, earning this herb titles such as “the longevity herb” (12) and “herb of immortality” (1). In modern applications, its highest antioxidant extracts are being used in cosmetics (13), and it has been demonstrated to improve hair health to prevent loss (14). Its neuroprotective properties have also made it popular for the prevention of age related cognitive decline and dementia (15).

Jiaogulan was originally listed as a survival food in Zhu Xiao’s Materia Medica for Famine in 1406 (46) before being listed for its medicinal applications in Li Shizhen’s Compendium of Materia Medica in 1596 (47). However, Li conflated this herb with a similar five leaf vine called wu lian mei (Cayratia japonica), and it was not until the 19th century that the botanist Wu Qijun realised Li’s error through a careful forensic analysis of the plants and their characteristics in relation to the texts and developed separate entries for both (10).

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