补肾益精方可减轻秀丽隐杆线虫β淀粉样蛋白沉积及氧化损伤OA

Objective:To investigate the protective effects of Chinese medicine Bushen Yijing Formula against amyloid β-protein(Aβ)deposition and oxidative damage using models of Caenorhabditis elegans.Methods:The C.elegans models,including wide-type strains N2,transgenic strains CL4176,TJ356,and LG333,were employed.The herbal components of the formula were water-extracted,freeze-dried into lyophilized powder,and added to the culture medium at different concentrations.Oxidative stress was induced by paraquat exposure.Evaluated parameters included lifespan;time to paralysis and pharyngeal Aβ deposition in CL4176;levels of total antioxidant capacity,superoxide dismutase(SOD),catalase(CAT),glutathione(GSH),malondialdehyde(MDA),and reactive oxygen species(ROS)measured by commercial kits;apoptosis detected by acridine orange staining;nuclear translocation of DAF-16::GFP in TJ356 nematodes and SKN-1::GFP in LG333 nematodes observed under fluorescence microscopy.Molecular docking and dynamics simulations were further performed to assess the binding stability of the active components catalpol and tetrahydroalstonine(THA)with the core targets FOXO and Nrf2.Results:Compared with the normal control group,Bushen Yijing Formula significantly extended the lifespan of N2 nematodes under both oxidative stress and normal conditions(all P<0.01).Compared with the control group of the AD model,Bushen Yijing Formula prolonged the time to paralysis and reduced pharyngeal Aβ deposition in CL4176(all P<0.01).Compared with the control group in the paraquat-induced oxidative stress model in N2,Bushen Yijing Formula elevated total antioxidant capacity,SOD,CAT,and GSH levels(all P<0.01),decreased MDA and ROS levels(all P<0.05),and attenuated apoptosis.Moreover,the formula promoted nuclear translocation of DAF-16 and SKN-1(all P<0.01).Molecular docking revealed that binding energies of catalpol and THA with FOXO and Nrf2 were all below-7.00 kcal/mol,and dynamics simulations confirmed high stability and favorable affinity for the FOXO-catalpol,Nrf2-catalpol,and Nrf2-THA complexes.Conclusion:Bushen Yijing Formula alleviates Aβ deposition and its neurotoxicity,enhances antioxidant capacity,and attenuates oxidative stress injury in model nematodes,likely through stable binding and regulation of the FOXO/Nrf2 signaling pathway.