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Oleanolic acid (OA) is a pentacyclic triterpene with reported protective effects against various diseases, including diabetes, hepatitis, and different cancers. However, the effects of OA on obesity‐induced muscle atrophy remain largely unknown. This study investigated the effects of OA on skeletal muscle production and proliferation of C2C12 cells. We report that OA significantly increased skeletal muscle mass and improved glucose intolerance and insulin resistance. OA inhibited dexamethasone (Dex)‐induced muscle atrophy in C2C12 myoblasts by regulating the PI3K/Akt signaling pathway. In addition, it also inhibited expression of MuRF1 and Atrogin1 genes in skeletal muscle of obese mice suffering from muscle atrophy, and increased the activation of PI3K and Akt, thereby promoting protein synthesis, and eventually alleviating muscle atrophy. Taken together, these findings suggest OA may have potential for the prevention and treatment of muscle atrophy. [ABSTRACT FROM AUTHOR]

Obesity is a common chronic metabolic disease that induces chronic systemic inflammation in the body, eventually leading to related complications such as insulin resistance (IR), type 2 diabetes mellitus, and metabolic syndromes such as cardiovascular disease. Exosomes transfer bioactive substances to neighboring or distal cells through autosomal, paracrine, or distant secretion, regulating the gene and protein expression levels of receptor cells. In this study, we investigated the effect of mouse bone marrow mesenchymal stem cell‐derived exosomes (BMSC‐Exos) on high‐fat diet obese mice and mature 3T3‐L1 adipocyte models of IR. BMSC‐Exo treatment of obese mice promoted their metabolic homeostasis, including reduction of obesity, inhibition of M1‐type proinflammatory factor expression, and improvement of insulin sensitivity. In vitro analysis revealed that BMSC‐Exos improved IR and lipid droplet accumulation in mature 3T3‐L1 adipocytes treated with palmitate (PA). Mechanistically, BMSC‐Exos cause increased glucose uptake and improved IR in high‐fat chow‐fed mice and PA‐acting 3T3‐L1 adipocytes by activating the phosphoinositide 3‐kinases/protein kinase B (PI3K/AKT) signaling pathway and upregulating glucose transporter protein 4 (GLUT4) expression. This study offers a new perspective for the development of treatments for IR in obese and diabetic patients. [ABSTRACT FROM AUTHOR]

When skeletal muscle is damaged, satellite cells (SCs) are activated to proliferate rapidly and fuse with the damaged muscle fibers to form new muscle fibers, thereby promoting muscle growth and remodeling and repair of trauma. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration. Therefore, we hypothesized that, when muscles are injured, myoblast‐derived exosomes may regulate muscle repair and regeneration. Here, we investigated the underlying mechanism by applying C2C12‐derived exosomes to injured mouse skeletal muscles. The expression levels of skeletal muscle regeneration factors paired box 7 and lipid‐promoting factor peroxisome proliferator‐activated receptor γ were upregulated, whereas the expression levels of fibrosis factors collagen‐1 and α‐smooth muscle actin decreased. The expression of proliferating cell nuclear antigen was elevated after applying C2C12‐derived exosomes to SCs. Application of C2C12‐derived exosomes to fibro‐adipogenic progenitors resulted in an increase in peroxisome proliferator‐activated receptor γ expression and adipogenesis capacity, whereas α‐smooth muscle actin expression and fibrosis capacity decreased. Analysis of the transcriptome and proteome of SCs after treatment with exosomes showed the involvement of multiple biological processes, including proliferation and differentiation of SCs, muscle regeneration, skeletal muscle atrophy, and the inflammatory response after muscle injury. Hence, our data suggest that C2C12‐derived exosomes can promote the regeneration of skeletal muscle fibers, accelerate the production of fat from damaged muscles, inhibit the fibrosis of damaged muscles, and accelerate injury repair, which is related to exosome‐mediated regulation of the proliferation of SCs, differentiation of fibro‐adipogenic progenitors, and modulation of SC mRNA expression and protein formation and decomposition. [ABSTRACT FROM AUTHOR]

Background: Acetaminophen (APAP) overdose represents one of the most common drug-induced liver injuries (DILI) worldwide. Oxidative damage to the hepatocytes and their resultant autophagy are the key components in the APAP-induced DILI. Echinacea purpurea polysaccharide (EPPS), the component extracted from the root of Echinacea purpurea (L.) Moench, shows various biological functions including immunoregulation and antioxidant activity.Purpose: This study aimed to elucidate the protective effect of EPPS against APAP-induced DILI and the underlying mechanisms.Results: EPPS attenuates APAP overdose induced DILI in mice and ameliorates inflammation and oxidative stress in mice with APAP overdose-induced DILI. Furthermore, EPPS protected the hepatocytes against APAP-induced liver injury by suppressing apoptosis. EPPS ameliorates APAP-induced DILI via an autophagy-dependent mechanism in vivo and increases autophagy with a reduction in oxidative stress and inflammation in vitro. Parkin knockdown prevents the autophagic-dependent manner of EPPS effects in APAP-treated hepatocytes.Conclusions: EPPS exhibited a strong hepatoprotective effect against APAP-induced DILI and was correlated with reduction of autophagy-dependent oxidant response, inflammation, and apoptosis. Moreover, the findings indicated that EPPS exerts its hepatoprotective effect against APAP mainly via Parkin-dependent autophagy, and the use of EPPS can serve as a promising novel therapeutic strategy for APAP-induced DILI. [ABSTRACT FROM AUTHOR]