Research Progress on the Hypoglycemic Effect of Gynostemma pentaphyllum Extract

1. Introduction 

Diabetes mellitus is a global metabolic disease characterized by hyperglycemia, with its incidence increasing year by year, which has become a serious public health problem. In the search for effective hypoglycemic drugs, traditional Chinese medicine (TCM) has shown great potential. Gynostemma pentaphyllum, also known as "Qiyedan" (Seven-leaf Ginseng) in Chinese, is a perennial herbaceous vine belonging to the genus Gynostemma of the Cucurbitaceae family. In traditional TCM, it is often used for clearing heat and detoxifying, replenishing qi and invigorating the spleen. In recent years, with the in-depth development of modern pharmacology research, the hypoglycemic effect of Gynostemma pentaphyllum has attracted increasing attention from the scientific community. The Gynostemma pentaphyllum extract contains a variety of active components, such as saponins, polysaccharides, and flavonoids, which exert hypoglycemic effects through multiple pathways and targets. It also has advantages such as low adverse reactions and abundant resources. This article aims to systematically review the active components, metabolic characteristics, mechanism of action, pharmacological research, and safety evidence of the hypoglycemic effect of Gynostemma pentaphyllum extract, and prospect its future research directions, so as to provide a theoretical reference for the development and application of Gynostemma pentaphyllum in the prevention and treatment of diabetes mellitus. 

2.  Active Components and Metabolic Characteristics 

 2.1 Core Components 

Gynostemma pentaphyllum Saponins (Gypenosides): Containing more than 80 kinds of dammarane-type saponins (e.g., Ginsenoside F2), they have a structure similar to ginsenosides and are the core substances regulating insulin secretion and signaling pathways. Gynostemma pentaphyllum Polysaccharides: By inhibiting the activities of α-amylase and α-glucosidase, they delay the decomposition of carbohydrates into glucose and reduce postprandial blood glucose fluctuations. Flavonoids (Homoeriodictyol, Rhamnetin): Molecular docking shows that the binding free energy of homoeriodictyol to key diabetic targets (e.g., MAPK8, PIK3CA) is -16.58 kcal/mol, which is better than that of metformin (-15.11 kcal/mol), suggesting a stronger potential for target regulation. 

2.2 Metabolic Rules 

After intestinal absorption, saponin components are metabolized into secondary glycosides in the liver; polysaccharides undergo microbial fermentation in the intestine to produce short-chain fatty acids (e.g., butyric acid), which assist in regulating glucose metabolism. Currently, the bioavailability of Gynostemma pentaphyllum extract is greatly affected by its dosage form, and the research and development of sustained-release preparations is still in the exploratory stage.

3. Core Mechanism of Hypoglycemic Effect of Gynostemma pentaphyllum Extract 

 Gynostemma pentaphyllum extract exerts hypoglycemic effects through multiple targets and pathways, with the main mechanisms including promoting insulin secretion, inhibiting glucose absorption, improving insulin sensitivity, and exerting antioxidant and anti-inflammatory effects. 

3.1 Regulation of Insulin Signaling Pathways 

Activation of the PI3K-Akt pathway: Helps muscle and adipose cells absorb glucose and improves insulin resistance (glucose uptake increased by 35% in animal experiments). 

Regulation of the AMPK pathway: Reduces glucose production in the liver, lowers fasting blood glucose, and at the same time enhances mitochondrial function and improves energy metabolism efficiency.

3.2 Promotion of Insulin Secretion 

Gynostemma pentaphyllum saponins (e.g., Phanoside) can stimulate insulin secretion from pancreatic β-cells in a dose-dependent manner. In in vitro experiments, 4 mg/mL of the extract increased insulin release from rat islet cells by 8 times. It can also protect the survival of β-cells by upregulating markers such as PDX1. 

3.3 Inhibition of Glycolytic Enzymes 

Inhibition of α-amylase: The inhibition rate of Gynostemma pentaphyllum polysaccharides on this enzyme reaches 50% of that of acarbose, delaying the hydrolysis of starch into glucose. 

Inhibition of α-glucosidase: In vitro experiments show that the inhibitory ability of the extract on this enzyme (IC₅₀=42.8 μg/mL) is better than that of acarbose (IC₅₀=53.9 μg/mL), which can delay the decomposition and absorption of sucrose and maltose. 

3.4 Antioxidant and Anti-Inflammatory Effects 

Flavonoid components can scavenge free radicals (e.g., superoxide anions) and reduce oxidative stress in diabetic mice (MDA decreased by 40%); they can also inhibit the NF-κB pathway, alleviate chronic inflammation, protect islet cells and vascular endothelium, and delay diabetic complications (e.g., vascular lesions). 

4. Progress in Pharmacological Research 

4.1 In Vitro and Animal Experiments 

Regulation of glucose metabolism: After treatment with Gynostemma pentaphyllum extract, the fasting blood glucose of diabetic model mice decreased by 25%~30%, glycated hemoglobin (HbA1c) improved by 15%~20%, and blood lipids (triglycerides, cholesterol) decreased significantly at the same time. Alleviation of complications: By inhibiting iNOS activity to reduce excessive NO production, it alleviates diabetic vascular lesions; it regulates gut microbiota (e.g., increasing the abundance of short-chain fatty acid-producing bacteria) and improves metabolic disorders related to insulin resistance.

4.2 Current Status of Clinical Research 

At present, only small-scale clinical trials support its hypoglycemic potential. For example, when patients with type 2 diabetes mellitus were supplemented with 300 mg of Gynostemma pentaphyllum saponin extract daily, their fasting blood glucose decreased by 12% after 12 weeks. However, there are problems such as small sample size and unstandardized dosage, and large-scale, multi-center randomized controlled trials (RCTs) are still needed. 

5. Safety Analysis 

Short-term safety: In animal experiments and small-scale clinical studies, when the daily dose was ≤1000 mg, only 15% of the subjects experienced mild gastrointestinal discomfort (e.g., abdominal distension), and no serious hepatic or renal toxicity was reported. Potential risks: Long-term safety data are lacking, and attention should be paid to the accumulation effect of saponin components; When used in combination with hypoglycemic drugs (e.g., metformin, insulin), it may enhance the hypoglycemic effect, so the risk of hypoglycemia should be vigilant, and it is recommended to use it under medical supervision.

6. Conclusion and Prospect 

Gynostemma pentaphyllum extract exerts hypoglycemic effects through multiple target mechanisms via saponins, polysaccharides, and flavonoids, including stimulating insulin secretion, inhibiting glycosidase activity, improving insulin sensitivity, and exerting anti-inflammatory and antioxidant effects. Animal experiments have confirmed its effect in regulating blood glucose and blood lipids, but high-quality clinical research is still lacking. 

Future research directions can be focused on the following aspects: Deepening monomer research: Analyzing the precise mechanism of action of homoeriodictyol and specific saponins (e.g., GP3, GP4) to develop targeted hypoglycemic drugs; Promoting clinical verification: Designing multi-center, large-sample trials to clarify the effective dosage, applicable population, and long-term safety; Optimizing preparations and combination use: Developing sustained-release preparations to improve bioavailability, exploring synergistic regimens with probiotics and hypoglycemic drugs, and promoting the transformation of natural products to clinical applications. 

References 

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