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Article Publish Status: FREE
Abstract Title:

20(s)‑ginseonside‑Rg3 modulation of AMPK/FoxO3 signaling to attenuate mitochondrial dysfunction in a dexamethasone‑injured C2C12 myotube‑based model of skeletal atrophy.

Abstract Source:

Mol Med Rep. 2021 May ;23(5). Epub 2021 Mar 2. PMID: 33649814

Abstract Author(s):

Manying Wang, Rui Jiang, Jianzeng Liu, Xiaohao Xu, Guang Sun, Daqing Zhao, Liwei Sun

Article Affiliation:

Manying Wang

Abstract:

Muscle atrophy, a side effect from administration of the anti‑inflammatory medication dexamethasone (DEX), is preventable by concomitant administration of the major monomeric constituent ofC.A. Meyer, 20(S)‑ginsenoside Rg3 (S‑Rg3). Putative S‑Rg3‑associated prevention of DEX‑induced muscle atrophy may involve S‑Rg3 mitigation of DEX‑induced mitochondrial dysfunction. In the present study, MTT assays revealed enhanced cell viability following S‑Rg3 treatment of DEX‑injured C2C12 myotubes. Subsequent PCR and western blotting results demonstrated S‑Rg3‑induced reduction of expression of muscle atrophy F‑box protein (atrogin‑1) and muscle RING‑finger protein‑1, proteins previously linked to muscle atrophy. Additionally, S‑Rg3 treatment of DEX‑injured myotubes ledto aggregation of Rg3 monomers in cells and dose‑dependent increases in cellular mitochondrial basal respiratory oxygen consumption rate and intracellular ATP levels compared with their levels in untreated DEX‑injured myotubes. In addition, S‑Rg3 treatment significantly reversed DEX‑inducedreductions of expression of key mitochondrial respiratory electron transport chain subunits of protein complexes II, III and V in DEX‑injured myotube cells. Furthermore, S‑Rg3 alleviation of mitochondrial dysfunction associated with DEX‑induced injury of C2C12 myotubes was linked to S‑Rg3‑associated decreases in both forkhead box O3 (FoxO3) protein expression and phosphorylation of AMP‑activated protein kinase (AMPK). Collectively, these results implicate S‑Rg3 modulation of signaling within the AMPK‑FoxO3 pathway as a putative mechanism underlying S‑Rg3 alleviation ofDEX‑induced muscle atrophy.

Study Type : Animal Study
Additional Links
Pharmacological Actions : Genoprotective : CK(477) : AC(177)
Problem Substances : Dexamethasone : CK(71) : AC(16)

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