Campanumoea javanica Bl. activates the PI3K/AKT/mTOR signaling pathway and reduces sarcopenia in a T2DM rat model

Abstract

Abstract Objective: Sarcopenia causes loss of skeletal muscle and function, thus seriously affecting the physical function and quality of life in the elderly. This article discusses the specific molecular mechanism and ameliorating effects of Tudangshen (TDS) on sarcopenia in elderly rats with type 2 diabetes mellitus (T2DM). Methods: Elderly Sprague-Dawley (SD) rats were randomly selected and fed with a high-fat diet combined with intraperitoneal injection of streptozotocin to establish T2DM model. The model rats were stratified and randomly divided into model group, metformin group, TDS high-dose group, TDS medium-dose group, and TDS low-dose group according to blood glucose combined with body weight, and the same batch of old SD rats were set as normal control group. The effects of TDS in an elderly T2DM sarcopenia rat model were evaluated by observing body positions of the rats, analyzing blood biochemistry, testing exercise capacity, and pathologically staining sectioned gastrocnemius muscle tissues. The molecular mechanisms of the effects were analyzed using quantitative real-time polymerase chain reaction and western blotting. Results: TDS has no statistically significant effect on blood glucose, insulin and glycosylated serum protein in aged rats with T2DM, but it can reduce levels of glycosylated serum protein, total cholesterol, triglycerides, and low-density lipoprotein; it improves pathological changes in rat gastrocnemius muscle tissues, and increases muscle cell activity in elderly rats with T2DM and sarcopenia. TDS also promoted the upregulation of the expression of mammalian target of rapamycin (mTOR)/protein kinase B (PKB/Akt)/phosphatidylinositol 3-kinase (PI3K)/ribosomal protein S6 kinase/eukaryotic initiation factor 4E binding rotein1 mRNA in rats and triggered an increase in corresponding protein levels. Conclusions: TDS alleviated muscle decline in elderly rats with T2DM by activating the PI3K/AKT/mTOR signaling pathway and regulating the synthesis of corresponding proteins.