12,23-Dione dammarane triterpenes from Gynostemma longipes and their muscle cell proliferation activities via activation of the AMPK pathway

Thi Kim Quy Ha,Darren R Williams,Da-Woon Jung,Won Keun Oh,Ha Thanh Tung Pham,Jun-Li Yang,Van On Tran,Hyo Moon Cho

doi:10.1038/s41598-018-37808-9

Abstract

The aging population is growing rapidly around the world and there is also an increase in sarcopenia, which is characterized by decreased muscle mass, strength and function in the elderly population. AMP-activated protein kinase (AMPK) is an essential sensor and regulator of glucose, lipid and energy metabolism throughout the body. Previous studies have shown that AMPK pathway activation by regular exercise and appropriate dietary control have beneficial effects on skeletal muscle. In the process of searching for new AMPK activators from medicinal plants, we isolated and characterized eight new 12,23-dione dammarane triterpenoids (1–3 and 5–9), as well as one known gypentonoside A from Gynostemma longipes. When all isolates were tested for their AMPK activation activities, seven compounds (1 and 3–8) were significantly activated AMPK phosphorylation in mouse C2C12 skeletal muscle cell lines. Since G. longipes contained a significant amount of active compound 1 (over 2.08% per dried raw plant), it suggested the potential of this plant to be developed as a functional food or botanical drug that enhances muscle proliferation by activating AMPK signaling pathways.

Highlights

One of the most distinctive effects of aging is the involuntary loss of muscle mass, strength and function, which is termed sarcopenia1
Compound 1 induced the expression of AMPK slightly at 24 hours after treatment (Supplementary Figs S55 and S56). These results suggested that triterpenoids from G. longipes could significantly stimulate the p-AMPK expression in both mouse C2C12 myotubes and myoblasts
We reported the findings of eight new 12,23-dione dammarane triterpenes from G. longipes, a traditional Vietnamese medicinal plant

Summary

Introduction

One of the most distinctive effects of aging is the involuntary loss of muscle mass, strength and function, which is termed sarcopenia. Skeletal muscle decreases approximately 3–8% per decade after 30 years of age, and muscle loss rapidly increases by about 25–30% after 60 years of age. Skeletal muscle decreases approximately 3–8% per decade after 30 years of age, and muscle loss rapidly increases by about 25–30% after 60 years of age2 This loss of muscle mass, strength and function is the key cause of many diseases in elderly people, and the increased risk of injury and falls due to sarcopenia can lead to continuous functional dependence and disability. The regenerative process in skeletal muscle tissue generally involves a coordinated sequence of the activation of satellite cells, which proliferate to produce a population of myogenic progenitors All isolates were evaluated for their enhancement effects on muscle proliferation through activation of the AMPK pathway using the C2C12 myoblast cell model

Methods

Results

Conclusion