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Jiaogulan

Scientific Name(s): Gynostemma pentaphyllum (Thunb.) Makino.
Common Name(s): Amachazuru (Japan), Dungkulcha (Korea), Five-leaf ginseng, Giao-co-lam tea (Vietnam), Herb of immortality, Immortal grass, Jiaogulan, Miracle grass, Penta tea, Poor man’s ginseng, Southern ginseng, Sweet tea vine, Twisting-vine orchid, Xiancao (China)

Clinical Overview

Use

Limited clinical studies have been conducted to support therapeutic applications. Jiaogulan may have a role in the management of type 2 diabetes, obesity, fatty liver disease, immune response (such as asthma), and cancer. G. pentaphyllum extracts may also have a place in beneficial antioxidant therapy.

Dosing

Clinical information is lacking. Jiaogulan tea (aqueous extract) 6 g/day, in divided doses twice a day 30 minutes before meals, has been studied in 2 clinical trials in patients with type 2 diabetes; 225 mg twice daily was used for 12 weeks in an antiobesity trial.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Severe nausea and increased bowel movements are possible.

Toxicology

No data available for human toxicity.

Botany

G. pentaphyllum (synonym: Vitis pentaphyllum) is a climbing, perennial vine native to China, Japan, and parts of Southeast Asia. The plant is dioecious—having both male and female flowers on separate plants. The leaves commonly grow in groups of 5, and small greenish-white florets are produced. Although a member of the gourd/cucumber family, G. pentaphyllum does not produce the characteristic fruit of this family. The plant grows abundantly and is harvested from the wild; it has been brought under cultivation and tissue culture has been achieved. The plant is now naturalized in the hotter, drier parts of the United States.1, 2, 3, 4

History

Jiaogulan has been incorporated into traditional Chinese medicine only in the last 20 years, although it has a history of folk use in the Guizhou province. Its properties are said to have been investigated when a Chinese census revealed a large number of elderly people in the province reported using the plant. The plant's potential as a sweetening agent stimulated chemical investigations in Japan. Commercialization and scientific study of the leaves have been promoted by provincial Chinese authorities, and the discovery that several ginseng-like saponins occur in the leaves has prompted aggressive promotion of the plant as a substitute for ginseng. The appearance of jiaogulan in American commerce has been heralded in popular publications.5, 6

Chemistry

Plant constituents primarily include sterols, acetylenic sterols, and triterpenols.7 The phenolic, saponin, and flavonoid composition is known to vary both geographically and by genotype.8 A large number of dammarane (triterpene) saponins, called gypenosides, have been elucidated from the plant leaves. Initial work on the gypenosides was undertaken primarily by 1 group of researchers, but constituents continue to be further described.9, 10, 11, 12, 13, 14 Several of these saponins are identical to those found in ginseng, and the content is comparable with that of ginseng roots. However, wide variation in the amount and nature of gypenosides has made standardization of specific gypenosides problematic. Most current products are standardized on total saponin content. High-performance liquid chromatography and liquid chromatography-mass spectrometry methods have been described to identify chemical constituents.15, 16

Uses and Pharmacology

Although jiaogulan contains ginseng-like saponins, it has not been reported to contain the other types of biologically active compounds, acetylenes, and polysaccharides found in ginseng. Thus, while ginseng pharmacology presents a reasonable starting point for investigation, jiaogulan cannot be considered as pharmacologically identical.

Antimicrobial

Limited antimicrobial activity has been shown for extracts of G. pentaphyllum.56

Antiobesity

A G. pentaphyllum leaf ethanol extract, actiponin, was shown in experimental studies to improve the expression of key regulatory factors of fat oxidation and lipogenic transcription factors in a dose-dependent manner. As a follow up to subsequent studies in mouse obesity models that demonstrated reduced body fat mass, a double-blind, randomized, placebo-controlled study was conducted in 80 obese participants with a BMI between 25 and 30 who had no other diagnoses. Compared to placebo, administration of actiponin 225 mg twice daily for 12 weeks led to significant improvements in abdominal fat and anthropometric parameters but not lipid parameters. Respectively, the gender-adjusted results for placebo compared to actiponin were abdominal fat (−2.87 vs −20.90 cm2, P=0.044), body weight (−0.08 vs −1.35 kg, P=0.021), BMI (0 vs −0.49, P=0.029), body fat mass (+0.28 vs −1.25; P<0.0001), percent body fat (+0.37 vs −1.16, P<0.0001), and waist circumference (−1.33 vs −2.49 cm; P=0.029). Actiponin was well tolerated with no adverse events reported.69

Antioxidant

Antioxidant activity has been described for jiaogulan extracts.14, 32, 33, 34, 35, 36, 57, 58 Cryoprotective effects on spermatozoa, possibly via antioxidant action, was demonstrated by a jiaogulan extract.59

Cancer

Animal data

An in vitro study of gypenosides in mice with leukemia showed increased survival for the treated mice.17

Clinical data

In vitro studies have evaluated the cytotoxicity of whole jiaogulan extracts as well as specific chemical constituents against various human cancer cell lines including brain, liver, oral, tongue, colon, and prostate cancers, and leukemia. Induction of cell cycle arrest and apoptosis has been demonstrated.8, 10, 12, 18, 19, 20, 21, 22, 23, 24, 25 However, clinical trials are lacking.

Cardiovascular

Animal data

The hot water extract of G. pentaphyllum was found to activate platelet aggregation; however, the active principle was not elucidated.26 Gypenosides inhibited platelet aggregation in another study.27 In rabbits, crude gypenosides decreased heart rate, increased stroke volume, dilated blood vessels, and reduced blood pressure while slightly increasing cardiac output.28 Purified gypenosides 5 and 10 were found to lower systolic and diastolic blood pressure, decrease coronary, brain, and peripheral blood vessel resistance, raise coronary flow, and lower heart rate in dogs.29 Crude gypenosides protected against cerebral ischemic damage in a rabbit model.30 Gypensoides protected the cardiac muscle in rats with diabetic cardiomyopathy as measured by left ventricular diastolic and systolic pressure.31

Clinical data

Clinical data regarding the use of jiaogulan for cardiovascular effects is lacking.

CNS

Antioxidant activity has been described for extracts of jiaogulan on nervous tissue samples.14, 32

Animal data

Extracts of G. pentaphyllum fed to rats appeared to protect hippocampus cells from hypoxia/hypoglycemia injury, suggesting a potential application in stroke or reperfusion injury.33, 34 Similarly, in rats with chronic cerebral hypoperfusion, gypenosides appeared to exert a protective effect.35 In rodent models of Parkinson disease, gypenosides were neuroprotective against oxidative injury.36, 37 Experimental learning deficits induced in mice were attenuated by Gynostemma aqueous extract and specific gypenosides.38, 39

Clinical data

Research reveals no clinical data regarding the use of jiaogulan for nervous system conditions.

Diabetes

Animal data

In obese mice, oral administration of G. pentaphyllum saponin extract over 8 weeks resulted in decreased body weight.40 A protective effect was observed by histology in rats with induced fatty liver disease fed jiaogulan.41 In mice with type 2 diabetes, high-dose G. pentaphyllum extract preserved insulin production and protected the pancreas (on histology).42

Clinical data

A small (N = 24) 12-week clinical trial evaluated the effect of jiaogulan tea 6 g/day in patients with type 2 diabetes. Decreases in fasting blood sugar, HbA1c and insulin resistance were observed. No effect on serum lipids was noted. No adverse effects were noted.43 A similar study (N = 25) conducted by the same researchers found the tea to be effective as add-on therapy to standard gliclazide treatment.44 A single-blind study evaluated the effect of 80 mL aqueous G. pentaphyllum extract daily over 6 months in nonalcoholic fatty liver disease, and found improvements in both insulin resistance and fatty liver scores.45

Hepatic

Animal data

A protectant effect against induced hepatic fibrosis in rats has been demonstrated.60, 61

Clinical data

A single-blind study evaluated the effect of 80 mL aqueous G. pentaphyllum extract daily over 6 months in nonalcoholic fatty liver disease, and found improvements in both insulin resistance and fatty liver scores. No other clinical studies were identified in a Cochrane systematic review on herbal medicines for fatty liver disease conducted 7 years later. 45, 68

Hyperlipidemia

Animal data

Results from animal experiments and in vitro studies are equivocal with some,11, 40, 46, 47 but not all,48 suggesting improved lipid profiles.

Clinical data

Similarly, limited clinical studies have produced conflicting data.43, 45, 49, 50, 69 Further quality trials are warranted. The influence of genetic polymorphisms on the metabolic response to consumption of G. pentaphyllum Makino tea was investigated in a small randomized interventional study in 66 hypercholesterolemic participants. Gene variants in 2 genes linked to dyslipidemia, apolipoprotein E (APOE) and cholesteryl ester transfer protein (CETP), were assessed. Although data from the 48 patients who completed the study revealed no significant interaction between tea consumption and APOE or CETP genotypes, G. pentaphyllum demonstrated beneficial effects on total cholesterol and fasting blood glucose in CETP B2 carriers compared to non-B2 carriers (P=0.045 and P=0.026, respectively) and on FBG in APOE non-E4 genotypes versus those with the E4 allele (P=0.042).67

Immune response (adaptogen)

In vitro studies suggest G. pentaphyllum extracts have an inhibitory effect on the interleukin response to allergens.13

Animal data

Studies in mice and rats have demonstrated moderation of the anti-inflammatory response by the immune system. Airway hyperresponsiveness was reduced in mice,51, 52 while thymus and spleen response to electric shock stress was muted in mice pretreated with oral extract for 14 days.53 A protective effect against the adverse effects of cadmium on T-cell functioning has also been demonstrated in rats.54

Clinical data

In an older study, cancer patients given jiaogulan granules after chemotherapy showed improved immune function by several end points.55 However, clinical data regarding the use of jiaogulan for immune effects is lacking.

Dosing

A dose of 3 to 9 g/day dried G. pentaphyllum leaves is recommended in traditional medicine.69 (Park, 2014)

Adaptogen

A 20 mg tablet containing 85% gypenosides 2 to 3 times a day is referred to in some texts as a preventive dose, and 60 mg taken 2 to 3 times a day as a treatment dose.6 However, published studies to justify this dosing are lacking.

Diabetes type 2

A small (N = 24) clinical trial evaluated the effect of jiaogulan tea (aqueous extract) 6 g/day taken in divided doses twice a day 30 minutes before meals.43

Nonalcoholic fatty liver disease

Aqueous G. pentaphyllum extract 80 mL daily over 6 months was used in a clinical study.45

Obesity

225 mg twice daily for 12 weeks was used in a double-blind, randomized, placebo-controlled study conducted in obese patients.69

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Although reports specifically on jiaogulan are lacking, caution is warranted as a few isolated ginsenosides have demonstrated embryotoxicity.

Interactions

Case reports are lacking. Older studies in animals suggested both pro- and antiaggregation action on platelets.26, 27

Adverse Reactions

Severe nausea and increased bowel movements have been reported;62 however, a clinical trial using jiaogulan tea 6 g/day reported no adverse effects.43

Toxicology

Chronic toxicity of jiaogulan was investigated in Wistar rats over 6 months. Doses from 6 mg to 750 mg/kg/day of the extract of the aerial plant parts were orally administered. No differences from controls were found for hematological indices, biochemistry, or histological studies.63 The median lethal oral dose (LD50) has been reported as 49 g/kg in rats, and intraperitoneal LD50 from 1 to 2 g/kg intraperitoneally in mice.64, 65, 66

References

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