International Journal of Drug Delivery Technology · Apr 28, 2026
Ursolic Acid Attenuates Glucocorticoid-Induced Sarcopenia: Molecular Mechanisms and Therapeutic Potential
By Arshad MZ, Mishra AP, Rajpoot A et al.
Sarcopenia is an age-associated disorder characterized by the progressive loss of skeletal muscle mass, strength, and functional capacity, leading to increased frailty, falls, and reduced quality of life in older adults. While aging is the main cause of primary sarcopenia, chronic glucocorticoid therapy significantly contributes to secondary sarcopenia. Muscle atrophy induced by glucocorticoids occurs through activation of catabolic pathways and suppression of anabolic processes. Glucocorticoids inhibit insulin-like growth factor-1 (IGF-1)/Akt signalling, suppress mammalian target of rapamycin (mTOR), activate forkhead box O (FOXO) transcription factors, upregulate E3 ubiquitin ligases atrogin-1 and MuRF1, enhance ubiquitin–proteasome degradation, induce myostatin expression, stimulate NF-κB–mediated inflammatory signalling, and promote oxidative stress and mitochondrial dysfunction. These changes shift the anabolic–catabolic balance toward protein degradation and functional decline. Ursolic acid (UA), a pentacyclic triterpenoid found in apple peels, Ocimum sanctum, and rosemary, has emerged as a promising compound capable of modulating these dysregulated pathways. UA activates Akt/mTOR signalling, inhibits FOXO-mediated proteolysis, suppresses atrogin-1 and MuRF1 expression, attenuates NF-κB activation, reduces reactive oxygen species production, enhances mitochondrial biogenesis via PGC-1α, and downregulates myostatin signalling. Preclinical models show preservation of muscle mass and strength following UA administration. Despite strong mechanistic evidence, development is limited by poor solubility, low bioavailability, and lack of clinical trials. This review examines the mechanisms of glucocorticoid-induced sarcopenia and evaluates ursolic acid as a pharmacological modulator