Damulin A

Damulin A: A Comprehensive Encyclopedic Reference

1. Identity: Chemical and Botanical Classification

Chemical Name and Structure

Damulin A is a novel dammarane-type triterpene saponin whose full systematic chemical name is 2α,3β,12β-trihydroxydammar-20(22)-E,24-diene-3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside]. G. pentaphyllum contains two novel dammarane-type saponins designated as damulin A (1), 2α,3β,12β-trihydroxydammar-20(22)-E,24-diene-3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside], and damulin B (2), 2α,3β,12β-trihydroxydammar-20,24-diene-3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside], that strongly activate AMPK in cultured L6 myotube cells.

Damulin A carries the molecular formula C₄₂H₇₀O₁₃ and a molecular weight of approximately 783.0 g/mol (CAS number 1202868-74-3). The compound belongs to the terpenoid chemical family and is classified as a saponin — specifically a glycosylated dammarane-skeleton triterpene.

Structural elucidation by NMR and mass spectrometry confirmed the compound's novelty. Through the determination of ¹H and ¹³C NMR structures at each position, the compound was determined as a novel compound and named "damulin A." In the ¹H-NMR spectrum, seven angular methyl groups show single peaks, and from proton peaks at 5.08 and 5.26 ppm it was determined that two glucoses are bonded in the compound. Damulins A and B differ only in the position of the double bond at C-20 of the side chain, with damulin A being the Δ20,22 isomer.

Damulin A is also related structurally to the broader class of gypenosides. Gypenoside XLVI was transformed into gypenoside L, gypenoside LI, damulin B, and damulin A by Lactobacillus bulgaricus, with a glucosyl at the C-20 position of gypenoside hydrolyzed, which led to increased bioactivity. Further investigation showed that damulin A is produced from gypenoside XLVI and gypenoside LVI by undergoing hydrolysis during heat treatment.

Botanical Source

Damulin A is found naturally in Gynostemma pentaphyllum (Thunb.) Makino, a dioecious, herbaceous climbing vine. Gynostemma pentaphyllum, also called jiaogulan (Chinese: 绞股蓝; pinyin: jiǎogǔlán; literally "twisting blue plant"), is a dioecious, herbaceous climbing vine of the family Cucurbitaceae widely distributed in South and East Asia as well as New Guinea. Among its many common names are five-leaf ginseng, poor man's ginseng, miracle grass, fairy herb, sweet tea vine, gospel herb, and southern ginseng.

Most species in this genus are distributed in China, tropical Asia (Vietnam, Thailand, and Malaysia), East Asia (Korea and Japan), Himalaya (India and Bangladesh), and New Guinea. Within the plant, damulin A is concentrated in the leaves and aerial parts. Jiaogulan (especially the leaves) contains several dammarane-type saponins.

Some gypenosides have structures identical to the ginsenosides found in ginseng, specifically ginsenosides Rb1, Rb3, F2, Rg3, Rc, Rd, malonyl-Rb1, and malonyl-Rd; the rest are closely related to the ginsenosides, and being discovered in Gynostemma, are customarily named as gypenosides.

Relationship to the Actiponin Extract

Damulin A is the primary analytical marker and active constituent of a standardized, commercially important heat-processed extract of G. pentaphyllum known as Actiponin®. The heat-processed GP extract named "Actiponin®" was approved as a functional ingredient for health functional foods by the Ministry of Food and Drug Safety of Korea in 2013. Actiponin® contains ten times the amount of damulin A (DA) and damulin B (DB), active ingredients with anti-obesity and anti-arthritic effects, compared to standard extracts of GP. The levels of damulins A and B, components responsible for AMPK activation, were increased by autoclaving in a time-dependent manner. Heat-processed G. pentaphyllum extract, actiponin, containing damulins A (0.93%, w/w) and B (0.68%, w/w), significantly stimulated fat oxidation and glucose uptake via AMPK activation in L6 myotube cells.

Common Forms and Preparations

Damulin A as an isolated pure compound is available commercially only as a research chemical or analytical reference standard; it is not available as a standalone dietary supplement for human use. The plant is used in folk medicine, typically as a herbal tea, but may be used as an alcohol extract or in dietary supplements. In consumer products, damulin A is delivered as part of standardized G. pentaphyllum extracts such as Actiponin® and ActivAMP®, available as capsules or tablets. The extraction process critically determines the damulin A content: a method using ultra-high performance liquid chromatography with tandem mass spectrometry for determination of the saponins also showed that the main saponins increased with increasing heating temperature and time.

---

2. Traditional and Historical Use

China — Ming Dynasty and Beyond

Gynostemma pentaphyllum (Thunb.) Makino, also known as "Jiao-Gu-Lan", has a long history of use as an edible plant in China as described in the book Herbs for Famine, published during the Ming Dynasty (1368–1644 AD). Throughout the Ming Dynasty (1368–1644 AD), the textbook "Herbs for Famine" recounts the plant's use as a vegetable, appropriate for eating or as a nutritional complement through starvation, rather than as a therapeutic herb.

The famous classical book of traditional Chinese medicine by Li Shizhen, the Compendium of Materia Medica, deeply and systematically summarized the usage and curative effect of GP. A renowned herbalist, Li Shi-Zhen, included this herb in his classical book, describing its use for hematuria, edema and pain of the pharynx, heat and edema of the neck, tumours, and trauma in 1578 AD.

People in the provinces of Guizhou, Guangxi, and Sichuan in the mountains of south central China have been using jiaogulan (called xiancao by locals) as a general health tonic and rejuvenating elixir. It was largely unknown outside of these mountainous regions until the early 1970s.

According to traditional Chinese medicine (TCM) ideas, G. pentaphyllum has a flavor and texture that is a little bit sour, balanced, warm, and strengthening, and the herb "would be utilized to boost barriers against illness and toward anti-inflammation." G. pentaphyllum is utilized in TCM for respiratory issues, heart palpitations, exhaustion syndrome, cleaning, anti-inflammatory, and purgative alleviation of coughing.

In China, G. pentaphyllum has been prescribed in Chinese medicines to treat various diseases, especially diabetes, referred to as "thirsty disease," for a long history from the Ming Dynasty (1368–1644 AD), and is mainly cultivated in Shaanxi, Guangxi, Fujian, Guizhou, and Hubei provinces today.

Japan

In Japan, Jiaogulan (Gynostemma pentaphyllum) is called Amachazuru, which translates as "sweet tea vine" due to a component in the leaves that give it a mildly sweet taste. It was precisely the herb's sweetness that led to research in Japan by Dr. Masahiro Nagai, a professor of pharmacognosy at Hoshi Pharmaceutical University, who was attempting to find alternative sweeteners to sugar in the late 1960s and early 1970s, analyzing the chemical compounds of Gynostemma in an effort to isolate the component responsible for its sweetness. In Japan, it is utilized as a stimulant and antipyretic.

Modern Chinese Research Context

A 1970s census in China showed a high percentage of centenarians, with low incidences of diseases that usually afflict the aging, in regions where jiaogulan was consumed daily. This started research on jiaogulan's possible anti-aging properties by the Chinese government. In 1972, the first study was conducted evaluating the therapeutic effects of the herb on 537 cases of chronic tracheobronchitis by the Research Group of Combined Traditional Chinese-Western Medicine of Qu Jing. Since then, over 300 scientific papers have been published, and Gynostemma pentaphyllum has been included in the Dictionary of Chinese Materia Medica.

---

3. Phytochemistry: Key Constituents and the Role of Damulin A

Major Phytochemical Classes in G. pentaphyllum

Chemical research indicates G. pentaphyllum primarily contains active ingredients including saponins, polysaccharides, and flavonoids. Saponins and polysaccharides are among the main active components, which have been extensively utilized in medicine, food, healthcare, and cosmetics due to their bioactivities including anti-tumor, anti-oxidation, hypoglycemic, cardioprotective, neuroprotective, and anti-inflammatory activities.

To date, 328 dammarane-type saponins have been isolated and structurally elucidated from Gynostemma species. Damulin A belongs to this large and structurally diverse class. Its two congeners isolated alongside it from heat-processed plant material are gypenoside L and gypenoside LI. Four constituents were isolated from heat-processed G. pentaphyllum using resin HP-20, silica gel, and reversed ODS column chromatography; they were identified by mass and NMR spectra as damulin A, damulin B, gypenoside L, and gypenoside LI.

G. pentaphyllum contains more than 20 active ingredients, including dammarane saponins, flavonoids, amino acids, and phytosterols, and has been reported to have antioxidant, anticancer, hepatoprotective, anti-atherogenic, and hypoglycemic effects.

Relationship of Damulin A to Gypenosides

Gypenosides (Gyps), a group of dammarane triterpene saponins primarily from Gynostemma pentaphyllum, have been identified as promising natural compounds with a diverse array of potent pharmacological activities. In the past two decades, a growing body of evidence has demonstrated that Gyps are crucial for the regulation of metabolic homeostasis, the reduction of oxidative stress and inflammation, the protection of the cardiovascular and hepatic systems, and the exhibition of anti-cancer potential.

Damulin A is specifically produced by partial hydrolysis of the more complex parent gypenosides during heat processing. The main saponins increased with increasing heating temperature and time, and further investigation showed that they were produced from gypenoside XLVI and gypenoside LVI by undergoing hydrolysis during the heat treatment.

---

4. Established Mechanisms of Action

4.1 AMPK Activation

The most thoroughly characterized mechanism of damulin A is the activation of AMP-activated protein kinase (AMPK), a cellular master energy sensor. AMPK is a key sensor and regulator of glucose, lipid, and energy metabolism throughout the body. Activation of AMPK improves metabolic abnormalities associated with metabolic diseases including obesity and type 2 diabetes.

G. pentaphyllum contains two novel dammarane-type saponins, damulin A and damulin B, that strongly activate AMPK in cultured L6 myotube cells. Damulins A and B also increased β-oxidation and glucose uptake with increasing GluT4 translocation to the plasma membrane in L6 myotube cells.

The downstream consequences of AMPK activation by damulin A include increased cellular glucose uptake via GLUT4 translocation and promotion of fatty acid β-oxidation. It is well known that the activation of AMPK also increases the glucose absorption into cells, and thus causes a blood glucose level-reducing effect. Activation of AMPK by damulins A and B may contribute to the beneficial effect of G. pentaphyllum on glucose and lipid metabolism.

The proposed mechanism of action of G. pentaphyllum is related to the AMPK-activating effects of the dammarane-type saponins. The mechanism of action of dammaranes, which involves the activation (phosphorylation) of AMPK, mimics the effects of physical exercise, including an up-regulation of autophagy with increased mitochondrial neogenesis.

4.2 Anti-Inflammatory Pathways

Pretreatment with Actiponin significantly suppressed the LPS-induced increase in nitric oxide (NO) and inducible nitric oxide synthase (iNOS) protein expression, and these effects were similar to those of damulin A and damulin B. AP, DA, and DB also significantly suppressed the expression of prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) protein, which were increased by LPS, in a concentration-dependent manner.

In osteoarthritis-relevant cellular models, in vitro studies showed that AP, DA, and DB reduced the expression of interleukin-1β alone-induced nitrite; inducible nitric oxide synthase; cyclooxygenase-2; matrix metallopeptidase 1/3/13; and a disintegrin and metalloproteinase with thrombospondin motifs 4/5. They also restored the expression of collagen type II and aggrecan, which are components of the extracellular matrix. The anti-arthritic effects of AP, DA, and DB were confirmed to be mediated by the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways.

4.3 Structural Features Underlying Bioactivity

To evaluate the efficacy of these four constituents, the MTT cytotoxicity assay was performed using A549 cells. Based on the structure of these four constituents, the results indicate that the hydroxyl group at C-2 and double bond at C20(21) and C20(22) positions are of importance in inhibition of A549 cell proliferation. Damulin F showed stronger cytotoxic activity against A549 cells with an IC₅₀ value of 19.8 ± 0.4 µM, whereas damulin E appeared to have weaker activity with an IC₅₀ value of 38.9 ± 0.6 µM. Therefore, saponins with a double bond at C20(21) exhibited stronger activities than saponins with a double bond at C20(22).

4.4 Intestinal Permeability

Damulins A and B exhibit low to moderate Caco-2 monolayer permeability with Papp values ranging from 1.33 (±0.073) to 6.2 (±0.248) × 10⁻⁶ cm/s. Damulins A and B differ only in the position of the double bond at C-20 of the side chain, with damulin A being the Δ20,22 isomer. Obstacles such as limited oral bioavailability, a lack of standardized extracts, and insufficient clinical data restrict the translational potential of gypenosides. These low to moderate permeability values suggest that oral bioavailability of damulin A as an isolated compound may be limited, a significant constraint on its pharmacological translation.

---

5. Scientific Evidence by Area of Use

5.1 Metabolic Health: Obesity, Body Composition, and Lipid Metabolism

Preclinical (In Vitro and Animal) Evidence

Damulin A's metabolic effects were first characterized in cell culture. Damulin A and damulin B increased β-oxidation and glucose uptake with increasing GluT4 translocation to the plasma membrane in L6 myotube cells. Taken together, these results indicate that activation of AMPK by damulin A and damulin B may contribute to the beneficial effect of G. pentaphyllum on glucose and lipid metabolism.

In animal models, oral administration of actiponin to ob/ob mice for 8 weeks decreased body weight gain, liver weight, and blood cholesterol levels with AMPK activation in the soleus muscle.

Clinical (Human) Evidence

The most directly relevant human clinical trial examined actiponin, the standardized extract in which damulin A serves as the principal active marker compound. The effects of actiponin, a heat-processed Gynostemma pentaphyllum extract, on body weight, fat loss, and metabolic markers were investigated in Korean participants in a 12-week, randomized, double-blind, placebo-controlled clinical trial.

Obese participants (BMI ≥ 25 kg m⁻² and WHR ≥ 0.90 for males or WHR ≥ 0.85 for females) who had not been diagnosed with any disease were recruited. The 80 subjects were randomly divided into actiponin (n = 40, 450 mg day⁻¹) and placebo (n = 40) groups.

During 12 weeks of actiponin supplementation, total abdominal fat area, body weight, body fat mass, percent body fat, and BMI were significantly decreased (P = 0.044, P < 0.05, P < 0.0001, P < 0.0001, and P < 0.05, respectively) in the actiponin group.

A subsequent randomized, double-blind, placebo-controlled trial examined a related standardized G. pentaphyllum extract (ActivAMP®) in a broader population. Although prior work focused on the overweight population (BMI < 30 kg m⁻²), the present trial included class 1 obese participants. Following 16 weeks of supplementation, the Gpp group had a significant reduction in total body weight, fat mass, and BMI compared to the placebo group.

Dyslipidemia: Systematic Review Evidence

A systematic review evaluated the lipid-lowering effect and safety of Gynostemma pentaphyllum (GP) used alone or as adjunctive therapy for dyslipidemia. Eight databases and three clinical trial registries were searched until January 2022; randomized controlled trials assessing the effectiveness of GP for dyslipidemia were included; trial quality was assessed using the Cochrane Risk of Bias Tool 2.0; data were analyzed by RevMan 5.4. Twenty-two RCTs involving 2,407 dyslipidemia participants were included. Regarding the risk of bias, 14 RCTs had some concerns, seven RCTs were high, and one trial was low. GP was comparable to n-3 fatty acids (RR 0.89, 95% CI 0.62–1.28) and red yeast rice (RR 0.33, 95% CI 0.1–1.12) on normalization of serum lipids.

Evidence strength assessment: Evidence linking damulin A specifically — rather than the whole extract — to metabolic effects in humans is indirect. The clinical trials involve standardized extracts containing multiple gypenosides; damulin A functions as the principal active and analytical marker, but no human trial has used isolated damulin A. Preclinical mechanistic data (AMPK activation, GLUT4 translocation, β-oxidation) are robust at the cell and animal level. The Phase II-level randomized controlled trial data on actiponin provide moderate-strength clinical evidence for body composition effects of the damulin A-enriched extract; larger, longer-term, and multi-center trials are needed.

5.2 Anti-Inflammatory and Anti-Arthritic Effects

Preclinical Evidence

The anti-arthritic effects of heat-processed Gynostemma pentaphyllum extract (Actiponin) and its derivatives, damulin A (DA) and damulin B (DB), were investigated using in vitro (primary rat chondrocytes and SW1353 cells) and in vivo (destabilization of the medial meniscus (DMM)-induced OA model) systems.

Histological analysis results from the in vivo study showed that the group that underwent DMM surgery induced degeneration by the loss of proteoglycan and the destruction of cartilage (OARSI score 14 ± 0.57), whereas the group that received AP daily for 8 weeks maintained an intact condition (OARSI score 5 ± 0.28 at 200 mg/kg, p < 0.001).

In the anti-inflammatory study, GP was extracted with 50% ethanol and heat-processed under high pressure to analyze the anti-inflammatory potential of the extract (actiponin) and its derived components, damulin A and damulin B, in RAW264.7 cells and carrageenan-induced rat models. Actiponin had no effect on RAW264.7 cells up to 180 μg/mL, but DA and DB showed cytotoxicity from 18 μM.

Collectively, these results suggest that actiponin is a potential therapeutic agent for mitigating OA progression and chondroprotection.

Evidence Strength Assessment

Anti-inflammatory and anti-arthritic evidence for damulin A remains at the preclinical stage (cell culture and rodent models). No human clinical trials isolating damulin A for arthritis outcomes have been published. The in vitro cytotoxicity observed for the isolated compound DA from 18 μM highlights a key distinction between isolated compound and whole-extract safety profiles relevant to any future clinical development.

5.3 Anticancer Activity

Preclinical (In Vitro) Evidence

An ethanol extract from heat-processed Gynostemma pentaphyllum showed more potent cytotoxic activity against human lung adenocarcinoma A549 cells than that of raw G. pentaphyllum. Heat-processed Gynostemma pentaphyllum and its main dammarane-type saponins — gypenoside L, gypenoside LI, damulin B, and damulin A — possess non-small cell lung carcinoma A549 cell inhibitory activity.

Four constituents — damulin A, damulin B, gypenoside L, and gypenoside LI — were isolated from heat-processed G. pentaphyllum. To evaluate the efficacy of these four constituents, the MTT cytotoxicity assay was performed using A549 cells. Based on the structure of these four constituents, the results indicate that the hydroxyl group at C-2 and double bond at C20(21) and C20(22) positions are of importance in inhibition of A549 cell proliferation.

The most notable pharmacological effects reported for the genus Gynostemma were anti-cancer, cardioprotective, hepatoprotective, neuroprotective, anti-diabetic, anti-obesity, and anti-inflammatory activities.

Evidence Strength Assessment

Anticancer evidence for damulin A is entirely preclinical and confined to in vitro cell-line assays. No animal studies specifically examining damulin A's anti-tumor effects in vivo (as an isolated compound) and no human clinical evidence have been reported. In vitro cytotoxicity against cancer cell lines is a very preliminary indicator and cannot be extrapolated to clinical efficacy. This area remains at the earliest stage of investigation.

5.4 Hepatoprotective Effects

Evidence for hepatoprotection relates to the broader G. pentaphyllum extract and gypenosides as a class, rather than damulin A specifically. G. pentaphyllum has a long history of use as a traditional medicine and dietary supplement in China. In vivo and in vitro studies have indicated that the ethanol extract exhibits a range of favorable bioactivities, including antioxidant, anti-inflammatory, and antilipidemic effects, suggesting that it can regulate hepatic cellular homeostasis. Gypenoside (GP), the predominant component of G. pentaphyllum, exhibits a therapeutic effect on chronic hepatic injury, fibrosis, and fatty liver disease via its anti-inflammatory and anti-oxidant activity.

Evidence strength assessment: No studies isolating damulin A for hepatoprotective endpoints in vivo or in clinical settings have been published. Available evidence pertains to the whole extract or gypenoside fractions.

---

6. Body Systems and Health Areas of Association

• Metabolic system: Glucose homeostasis, lipid metabolism, fat oxidation, body weight/composition via AMPK activation.
• Musculoskeletal system: Cartilage protection, suppression of matrix-degrading enzymes in osteoarthritis models, anti-arthritic activity.
• Oncology (preclinical): Inhibition of non-small cell lung carcinoma (A549) cell proliferation in vitro.
• Hepatic system: Associated (at the extract level) with hepatoprotective and antilipidemic effects.
• Cardiovascular system: Extracts have shown significant activities against coronary spasm and arrhythmia, diabetes, and the development of cancerous cells. The saponin-rich extracts also exhibited activities against platelet aggregation and inhibited the growth of Streptococcus mutans and Helicobacter pylori.
• Inflammatory pathways: Suppression of NO, iNOS, COX-2, PGE2, and NF-κB-mediated signaling.

---

7. Dosage Forms and Reported Dosages

No clinical studies have been conducted with isolated, purified damulin A as a single-compound intervention. Dosage data are therefore available only for standardized G. pentaphyllum extracts in which damulin A content has been characterized.

• Actiponin® (450 mg/day) — human RCT: The 80 subjects were randomly divided into actiponin (n = 40, 450 mg day⁻¹) and placebo (n = 40) groups over 12 weeks in the Park et al. (2014) randomized controlled trial.
• Damulin A content in Actiponin® — analytical characterization: Actiponin containing damulins A (0.93%, w/w) and B (0.68%, w/w) significantly stimulated fat oxidation and glucose uptake via AMPK activation in L6 myotube cells. At 450 mg/day of actiponin, this corresponds to approximately 4.2 mg/day of damulin A.
• Animal model (actiponin — oral gavage in OA model): The group that received AP daily for 8 weeks maintained an intact cartilage condition (OARSI score 5 ± 0.28 at 200 mg/kg, p < 0.001).
• Animal model (ob/ob mice — anti-obesity): Oral administration of actiponin to ob/ob mice for 8 weeks decreased body weight gain, liver weight, and blood cholesterol levels with AMPK activation in the soleus muscle.
• In vitro cytotoxicity — RAW264.7 macrophage cells: Actiponin had no effect on RAW264.7 cells up to 180 μg/mL, but DA and DB showed cytotoxicity from 18 μM.

---

8. Safety Considerations

8.1 Preclinical Safety Profile of G. pentaphyllum Extract

Toxicological studies were conducted on G. pentaphyllum, showing that the plant extracts were relatively safe in both acute and long-term toxicity experiments at the given dosage. The water extract was prepared and standardized, and the dry powder yielded 6% gypenosides. In the acute oral toxicity test, a single oral dose of 5,000 mg/kg of G. pentaphyllum extract was given to female Sprague-Dawley rats. In the subchronic toxicity test, an oral dose of 1,000 mg/kg/day of the extract was given to rats for 90 days. Standardized extract of G. pentaphyllum did not cause death or any toxic signs in rats.

Standardized extract of Gynostemma pentaphyllum did not produce mortality or any abnormality in rats.

8.2 Clinical Safety Signal from Human Trials

In a systematic review of dyslipidemia RCTs, the common adverse events of Gynostemma pentaphyllum included abdominal pain and abdominal distention. The adverse event rate of Gynostemma pentaphyllum was significantly lower than that of lipid-lowering agents. No serious adverse effects from Gynostemma pentaphyllum were documented in the included trials.

8.3 Cytotoxicity of Isolated Damulin A

An important safety-relevant distinction exists between the whole extract and the isolated compound. Actiponin had no effect on RAW264.7 cells up to 180 μg/mL, but isolated DA and DB showed cytotoxicity from 18 μM. This in vitro cytotoxicity at the isolated compound level is not observed at the concentrations present within standardized whole-plant extracts administered in published clinical trials, and it does not appear to have produced clinical adverse events in trials using actiponin. This distinction, however, underscores why isolated damulin A is currently classified as a research chemical rather than a direct-use supplement.

8.4 Evidence Gaps and Known Limitations

Obstacles such as limited oral bioavailability, a lack of standardized extracts, and insufficient clinical data restrict the translational potential of gypenosides. No published human data exist on the pharmacokinetics (absorption, distribution, metabolism, excretion) of isolated damulin A in humans. The clinical trials conducted to date have used standardized extracts, not the isolated compound; any safety or efficacy attribution to damulin A alone requires further investigation.

Some limited research has assessed the potential for jiaogulan to affect disorders such as cardiovascular diseases, hyperlipidemia, or type 2 diabetes, but these studies were too preliminary to allow any conclusion that it was beneficial. This Wikipedia-cited note reflects the overall assessment that, while mechanistic data are encouraging, the clinical evidence base remains limited in scale and methodological quality.

---

References

• Nguyen PH et al. "New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum." PubMed, PMID 21978948 (2011).
• PubChem. "Damulin A." CID 57393857. National Center for Biotechnology Information (NCBI).
• Park SH et al. "Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): A randomized, double-blind, placebo-controlled trial." Obesity 22:63–71 (2014).
• Inhibitory Effects of Heat-Processed Gynostemma pentaphyllum Extract (Actiponin®) and Its Components on Cartilage Breakdown in Osteoarthritis. Int. J. Mol. Sci. 2025, 26, 1728. PMC11855050.
• Exploring the Anti-Inflammatory Activity of the Heat-Processed Gynostemma pentaphyllum Extract (Actiponin®) in RAW264.7 Cells and Carrageenan-Induced Rat Models. PMC12470914.
• 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. PMC9291581.
• Gynostemma pentaphyllum for dyslipidemia: A systematic review of randomized controlled trials. PMC9459123.
• Caco-2 Cell Permeability of Flavonoids and Saponins from Gynostemma pentaphyllum: the Immortal Herb. ACS Omega (2020).
• Dammarane-type saponins from heat-processed Gynostemma pentaphyllum show fortified activity against A549 cells. PubMed PMID 23508742. Archives of Pharmacal Research (2013).
• Determination by UPLC-MS of four dammarane-type saponins from heat-processed Gynostemma pentaphyllum. Bioscience, Biotechnology, and Biochemistry (2014).
• Gynosaponin TN-1 producing from the enzymatic conversion of gypenoside XLVI by naringinase and its cytotoxicity on hepatoma cell lines. Food and Chemical Toxicology (2018).
• Gynostemma pentaphyllum: A review on its traditional uses, phytochemistry and pharmacology. ScienceDirect (2024).
• Gynostemma Pentaphyllum ameliorates CCl4-induced liver injury via PDK1/Bcl-2 pathway. PMC11094861.
• Gypenoside attenuates hepatic ischemia/reperfusion injury in mice via anti-oxidative and anti-apoptotic bioactivities. PMC3991488.
• Toxicity evaluation of standardized extract of Gynostemma pentaphyllum Makino. PubMed PMID 23796877.
• US Patent 8357786 – Method for preparing Gynostemma pentaphyllum extract with increasing damulin A and damulin B contents. USPTO.
• Gynostemma pentaphyllum. Wikipedia (accessed 2026).
• Gynostemma pentaphyllum an immortal herb with pharmacological properties. International Journal of Food Properties (2023).