Carnosic acid ameliorates alcohol-induced liver injury in animal models:experimental verification and molecular mechanism prediction
摘要Alcoholic liver disease(ALD),a pervasive global health concern,involves multifaceted pathological mechanisms including oxidative stress,lipid dysregulation and inflammatory responses,yet lacks effective multi-target therapies.Carnosic acid(CA),a natural diterpenoid with extensively characterized antioxidant and anti-inflammatory properties,remains underexplored for its systemic therapeutic potential in ALD.This study aimed to comprehensively investigate CA's hepatoprotective efficacy and molecular mechanisms against ALD.Results demonstrated that CA significantly reduced serum total cholesterol,triglycerides,and transaminase levels in ALD mice,concurrently alleviating alcohol-induced histopathological damage.Network pharmacology identified 36 potential targets,with 10 core targets predominantly enriched in lipid metabolism,PPAR signaling and inflammatory response.Molecular docking revealed superior binding affinities of CA to core targets compared to silibinin,a reference hepatoprotectant.RT-qPCR validation further confirmed CA's regulatory effects on apoptosis-related TP53/BCL2 axis,TNF-mediated inflammatory pathways and cytochrome P450(CYP450)metabolic genes.Through a tripartite strategy integrating phenotypic validation,mechanistic prediction,and experimental confirmation,this study elucidates CA's multi-target therapeutic actions against ALD via coordinated modulation of lipid homeostasis,oxidative stress and inflammatory pathways,providing the groundwork for future mechanism exploration.
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