handelin

Handelin is a natural small-molecule sesquiterpene-derived compound isolated from Chrysanthemum indicum that has shown preclinical activity in skeletal muscle, where it promotes myogenic differentiation and preserves muscle mass and function in models of cachexia, inflammation, and aging. In vitro, handelin upregulates early (MyoD, myogenin) and late (myosin heavy chain) myogenic markers, enhances mitochondrial respiration, activates IGF1/AKT signaling, reduces atrogin-1 expression, and inhibits NF-κB activation while lowering pro-inflammatory cytokines (IL-6, IL-1β, CXCL1) in TNF-α–induced myotube atrophy. In vivo, handelin mitigates LPS-induced cachexia by increasing body weight and soleus muscle mass and cross-sectional area with improved motor function, and in aged mice it increases muscle fiber cross-sectional area and upregulates Igf1, Il10, mitochondrial biogenesis and antioxidant genes, with increased SOD and catalase activity and reduced oxidative damage; its protective effects are dependent on Hsp70, as Hsp70 knockdown or pharmacologic inhibition abrogates benefits. These data suggest a mechanism involving anti-inflammatory, pro-myogenic, and mitochondrial-supporting actions with Hsp70 dependence and IGF1/AKT pathway engagement; development status is preclinical with no approved indications to date.[1]

Other names

8,8′-bioxo-β,β′-dimethyl-1,1′-bi-2,3,4,5,6,7-hexahydroazulenylidenebioactive compound from Chrysanthemum indicum