Bavachin and Corylifol A Improve Muscle Atrophy by Enhancing Mitochondria Quality Control in Type 2 Diabetic Mice

Abstract

Type 2 diabetes reduces muscle mass and function. Chronic inflammation and mitochondrial dysfunction play critical roles in muscle atrophy pathogenesis. Here, we investigated the effects of bavachin and corylifol A from Psoralea corylifolia L. seeds on muscle atrophy in dexamethasone-treated mice and in db/db mice. Bavachin and corylifol A enhanced muscle strength and muscle mass in dexamethasone-treated mice. In diabetic mice, they enhanced muscle strength and cross-sectional areas. Bavachin and corylifol A suppressed inflammatory cytokine (interleukin-6 and tumor necrosis factor-α) expression levels by downregulating nuclear factor-κB phosphorylation. They decreased the muscle atrophic factor (myostatin, atrogin-1, and muscle RING finger-1) expression levels. They activated the AKT synthetic signaling pathway and induced a switch from fast-type glycolytic fibers (type 2B) to slow-type oxidative fibers (types I and 2A). They increased mitochondrial biogenesis and dynamic factor (optic atrophy-1, mitofusin-1/2, fission, mitochondrial 1, and dynamin 1-like) expression levels via the AMP-activated protein kinase–peroxisome proliferator-activated receptor gamma coactivator 1-alpha signaling pathway. They also improved mitochondrial quality by upregulating the mitophagy factor (p62, parkin, PTEN-induced kinase-1, and BCL2-interacting protein-3) expression levels. Therefore, bavachin and corylifol A exert potential therapeutic effects on muscle atrophy by suppressing inflammation and improving mitochondrial function.

Exosomal miR-125b-5p derived from adipose-derived mesenchymal stem cells enhance diabetic hindlimb ischemia repair via targeting alkaline ceramidase 2

“…Lower limb ischemia is a common complication of diabetes and the leading cause of non-traumatic amputation [ 29 ]. Skeletal muscle, which has high metabolic activity, is particularly vulnerable to microcirculatory dysfunction and obstruction, leading to ischemia and hypoxia injury [ 30 – 32 ]. Vascular endothelial damage and the accumulation of advanced glycation end products (AGEs) further exacerbate the injury under diabetic conditions [ 33 ].…”

Mitochondrial Dysfunction, Oxidative Stress, and Inter-Organ Miscommunications in T2D Progression

“…Whether the decline of mitophagy is a cause or consequence of prediabetes progression into T2D remains to be determined. Although insulin-sensitizing lifestyle interventions of exercise and dietary restrictions [116] have been associated with recovering PINK1 and PARKIN in HFD-exposed IR models, emerging pre-clinical studies with flavonoids such as Bavachin and corylifol A in db/db mice [117], and isoflavonoid puerarin in palmitate-exposed L6 myotubes [118] also demonstrated improved insulin sensitivity with restored PARKIN/PINK1 activity. Although further therapeutic studies in the context of prediabetes and T2D are required, the evidence so far suggests that boosting mitophagy in the prediabetes stage could protect against accumulating mitochondrial damage and may serve as a useful preventative treatment.…”

The role of mitophagy in metabolic diseases and its exercise intervention

“…Additionally, it downregulated the expression of myostatin (MSTN), atrogin-1, and muscle-specific RING finger protein 1 (MuRF-1), activated the Akt synthesis signaling pathway, reduced blood glucose level, and increased the muscle mass of diabetic muscular dystrophy mice. In addition, Bavachin and Corylifol A administration can activate mitophagy, inhibit OS, and thus improve mitochondrial quality by upregulating LC3-II, p62, Parkin, PINK1, and BNIP3 protein expression in muscle tissues of diabetic muscular dystrophy mice ( Yeon et al, 2023 ).…”