Chinese Medicine · 15 authors, 6 centres
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A drug repositioning screen of an FDA-approved library of approximately 3000 compounds identified honokiol as an effective anti-NAFLD candidate in preclinical in vitro and in vivo models. Honokiol directly binds to the AMPKγ1 subunit to activate AMPK signaling, inhibiting metabolic syndrome and NAFLD progression including hepatic steatosis, liver fibrosis, adipose inflammation, and insulin resistance.
A drug repositioning strategy was used to screen an FDA-approved drug library with approximately 3000 compounds in an in vitro hepatocyte model of lipid accumulation, identifying honokiol as an anti-NAFLD candidate. Honokiol significantly inhibited metabolic syndrome and NAFLD progression in multiple in vitro and in vivo models, evidenced by improved hepatic steatosis, liver fibrosis, adipose inflammation, and insulin resistance. Mechanistically, honokiol directly bound to the AMPKγ1 subunit to activate AMPK signaling rather than acting on classical upstream regulators. Mutation of honokiol-binding sites of AMPKγ1 largely abolished the protective capacity. No side effects on the cardiovascular system were observed.
