黄芩素延缓衰老的多模型药效学评价及基于网络药理学的机制初探OA

Objective To systematically evaluate the in vitro antioxidant activity of baicalein,its in vivo efficacy in model animals,and its anti-aging effects at the cellular level,and further predict its core targets and pathways.Methods The in vitro antioxidant activity of baicalein was determined using 2,2-Diphenyl-1-picrylhydrazyl(DPPH)and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt(ABTS)radical scavenging assays.Caenorhabditis elegans was used as the model organism.Negative control,vitamin C group,and different baicalein treatment groups(10-8,10-6,and 10-4 mol/L)were established.The lifespan,stress resistance,locomotor capacity,and brood size were measured,and the levels of malondialdehyde(MDA)and lipofuscin were detected.HaCaT cell models of H₂O₂-induced oxidative damage and UVB-induced photoaging were established,and the protective effects on cells were evaluated using methyl thiazolyl tetrazolium(MTT)assay,DCFH-DA fluorescence probe method,and SA-β-gal staining.Common targets between baicalein and aging were identified via network pharmacology,and analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The binding affinity of core targets was further validated by molecular docking.Results Baicalein exhibited scavenging activity against DPPH and ABTS free radicals.Compared with the negative control,10-4 mol/L baicalein prolonged the mean lifespan of nematodes(P<0.001),improved their survival rates under heat,oxidative,and ultraviolet stress(P<0.01),increased the frequencies of head thrashing and pharyngeal pumping(P<0.01),decreased the level of MDA and lipo-fuscin(P<0.01),and had no effect on brood size.Baicalein significantly increased the viability of HaCaT cells after H₂O₂-induced damage(P<0.001),reduced intracellular ROS level(P<0.01),and decreased the proportion of SA-β-gal-positive cells induced by UVB irra-diation(P<0.01).A total of 19 common targets were identified,including SIRT1,ESR1,and MAPK3.Enrichment analyses revealed that these targets were primarily involved in VEGF,EGFR tyrosine kinase inhibitor resistance,and cellular senescence pathways.Molecular docking further indicated that baicalein had the strongest binding affinity to ESR1.Conclusion Baicalein can exhibit anti-aging activity in multiple models,extending lifespan,enhancing stress tolerance,and alleviating oxidative damage and photoag-ing.Network pharmacology predicts that baicalein may regulate the VEGF,EGFR,and cellular senescence pathways through SIRT1 and ESR1.