Glucocorticoid-induced skeletal muscle atrophy is characterized by progressive loss of muscle mass and function, yet effective pharmacological interventions remain limited. Prostaglandin E 2 (PGE 2 ) plays an important role in maintaining muscle regeneration, and its degradation is primarily controlled by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Here we investigated whether phillyrin, a natural lignan compound, protects against dexamethasone (DEX)-induced muscle atrophy in mice. Phillyrin treatment significantly attenuated DEX-induced reductions in muscle mass and improved grip strength and motor endurance. Histological analysis showed that phillyrin alleviated myofiber atrophy and preserved mitochondrial ultrastructure. Mechanistically, phillyrin suppressed the upregulation of 15-PGDH and restored intramuscular PGE 2 levels, accompanied by recovery of EP4 signaling. These changes were associated with inhibition of FOXO3a-mediated proteolysis and partial restoration of mTOR and PGC-1α signaling in skeletal muscle. Collectively, these findings indicate that phillyrin protects against glucocorticoid-induced muscle atrophy, potentially through modulation of the 15-PGDH/PGE 2 pathway. These findings suggest that phillyrin may represent a potential therapeutic candidate for the treatment of glucocorticoid-induced skeletal muscle atrophy.
Zhaoyun Zong,Jing Liu,Ning Wang,Changmei Yang,Qingtao Wang,Wenhao Zhang,Yuling Chen,Xiaohui Liu,Haiteng Deng
Liver fibrosis is a reversible wound-healing response to acute or chronic liver injury that can progress to cirrhosis and liver cancer. Finding new strategies for prevention and management of liver fibrosis is urgently needed. It is known that hepatic stellate cell (HSC) is the primary source of extracellular matrix that drives liver fibrosis progression. Herein, we carried out a comprehensive secretome profiling to identify NMN-induced changes in secretory proteins and found that NMN suppressed the secretion of profibrotic protein and oxidoreductase in activated HSC (LX-2) cells, while real-time quantitative PCR analysis revealed that NMN downregulated profibrotic gene expression, resulting in HSC inactivation. Next, we demonstrated that nicotinamide mononucleotide (NMN) reduced the accumulation of liver extracellular matrix in thioacetamide (TAA) and carbon tetrachloride (CCl 4 ) induced mouse models for liver fibrosis. Furthermore, we determined that NMN inhibited oxidation-mediated 15-PGDH degradation to promote prostaglandin E 2 degradation and suppress HSC activation. In summary, our results propose that NMN supplementation is a new therapeutic approach for liver fibrosis prevention.
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