New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum

Nguyen, Phi Hung; Rehman, Gauhar; Hwang, Seung Lark; Đào, Trọng Tuấn; Park, Dong Chan; Kim, Ji Eun; Song, Hebok; Huh, Tae Lin; Oh, Won Keun

doi:10.1016/j.bmc.2011.09.013

Cited by 41 publications

(42 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current clinical study, participants who completed the 12-week of treatment with actiponin (450 mg/day) showed statistically significant reductions in abdominal fat (total abdominal fat area) and anthropometric parameters (weight, BMI, body fat mass, percent body fat, and waist circumference) without any significant changes in food intake, dietary, or lifestyle compared to the placebo group. These results were similar to our previous observations made in cultured cells and ob/ob mice both in vitro and in vivo (17,18). These observations suggest that AMPK activators, such as damulin A and B, in actiponin might be successfully delivered to peripheral tissues and exert anti-obesity effect in human subjects as similar to the result obtained in rodent model (18), although we did not analyze changes of AMPK activity in human tissues of actiponin and placebo groups.…”

Section: Discussionsupporting

confidence: 90%

See 1 more Smart Citation

Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): A randomized, double‐blind, placebo‐controlled trial

Park

Huh

Kim

et al. 2013

Obesity

View full text Add to dashboard Cite

Objective: The effects of actiponin was investigated, a heat-processed Gynostemma pentaphyllum extract, on body weight, fat loss, and metabolic markers of Korean participants in a 12-week, randomized, double-blind, placebo-controlled clinical trial. Design and Methods: Obese participants (BMI 25 kg m 22 and WHR 0.90 for male or WHR 0.85 for female) who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 80 subjects were randomly divided into actiponin (n 5 40, 450 mg day 21 ) and placebo (n 5 40) groups. Outcomes included measurement of efficacy (abdominal fat distribution, anthropometric parameters, and blood lipid profiles) and safety (adverse events, laboratory test results, electrocardiogram data, and vital signs). Results: During 12-week of actiponin supplementation, total abdominal fat area, body weight, body fat mass, percent body fat, and BMI were significantly decreased (P 5 0.044, P < 0.05, P < 0.0001, P < 0.0001, and P < 0.05, respectively) in the actiponin group compared to the placebo group. No clinically significant changes in any safety parameter were observed. Conclusion: Our study revealed that actiponin is a potent antiobesity reagent that does not produce any significant adverse effects. These results suggest that actiponin supplementation may be effective for treating obese individuals.

show abstract

Section: Discussionsupporting

confidence: 90%

“…These activities likely overlap with diverse downstream effects on AMPK activation (9). In vitro studies revealed that damulin A and B, two dammaranetype saponins purified from the leaves of G. pentaphyllum, are able to increase the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) through which b-oxidation can be stimulated (17).…”

Section: Introductionmentioning

confidence: 99%

Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): A randomized, double‐blind, placebo‐controlled trial

Park

Huh

Kim

et al. 2013

Obesity

View full text Add to dashboard Cite

show abstract

“…Gyp-L has been demonstrated to act as a potential activators of AMP-activated protein kinase [35, 36]. Previous study by Piao et al has simply explored the anticancer activity of Gyp-L in human lung cancer cells [37].…”

Section: Discussionmentioning

confidence: 99%

Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release

Liao

Zheng

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Esophageal cancer is one of the leading cause of cancer mortality in the world. Due to the increased drug and radiation tolerance, it is urgent to develop novel anticancer agent that triggers nonapoptotic cell death to compensate for apoptosis resistance. In this study, we show that treatment with gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, induced nonapoptotic, lysosome-associated cell death in human esophageal cancer cells. Gyp-L-induced cell death was associated with lysosomal swelling and autophagic flux inhibition. Mechanistic investigations revealed that through increasing the levels of intracellular reactive oxygen species (ROS), Gyp-L triggered protein ubiquitination and endoplasm reticulum (ER) stress response, leading to Ca2+ release from ER inositol trisphosphate receptor (IP3R)-operated stores and finally cell death. Interestingly, there existed a reciprocal positive-regulatory loop between Ca2+ release and ER stress in response to Gyp-L. In addition, protein synthesis was critical for Gyp-L-mediated ER stress and cell death. Taken together, this work suggested a novel therapeutic option by Gyp-L through the induction of an unconventional ROS-ER-Ca2+-mediated cell death in human esophageal cancer.

show abstract

“…Both compounds have a four ring triterpenoidic moiety conjugated to a carbohydrate domain. Damulin increases β-oxidation and exhibits a stimulatory effect on the rate of glucose uptake by upregulating GLUT4 translocation to the plasma membrane in L6 myotubes [48]. The range of minimal active concentrations of the compound in different assays presented in the manuscript was between 3 and 37 μM and this is quite adequate for in vitro assays.…”

Section: Diabetes Obesity and Hyperlipidimiamentioning

confidence: 97%

Activators of AMPK: Not Just for Type II Diabetes

2014

View full text Add to dashboard Cite

Recent discoveries of AMPK activators point to the large number of therapeutic candidates that can be transformed to successful designs of novel drugs. AMPK is a universal energy sensor and influences almost all physiological processes in the cells. Thus, regulation of the cellular energy metabolism can be achieved in selective tissues via the artificial activation of AMPK by small molecules. Recently, special attention has been given to direct activators of AMPK that are regulated by several nonspecific upstream factors. The direct activation of AMPK, by definition, should lead to more specific biological activities and as a result minimize possible side effects.

show abstract

New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum

Cited by 41 publications

References 32 publications

Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): A randomized, double‐blind, placebo‐controlled trial

Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): A randomized, double‐blind, placebo‐controlled trial

Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release

Activators of AMPK: Not Just for Type II Diabetes

Contact Info

Product

Resources

About