Study on the pharmacological effects and mechanism of Gegen-Zhimu herb pair in preventing and treating Alzheimer's disease by UHPLC-Q/TOF-MS metabolomics strategy
Objective To evaluate the efficacy of Puerariae lobatae radix(PLR)and Anemarrhenae Rhizoma(AR)in preventing and treating Alzheimer's disease(AD)and explore its potential mechanism of action by LC-MS serum metabolomics strategy.Methods The AD rat model was established by administering aluminum chloride(AlCl3)and D-galactose(D-gal)for 20 weeks.The traditional Chinese medicine intervention group was given the PLR,AR,and PLR-AR extracts for 8 weeks by gavage.The model effect and efficacy were evaluated by Morris water maze test and biochemical indicators including SOD,NO,and MDA;Metabolomics research based on the UHPLC-Q/TOF-MS method was conducted,and relevant metabolic pathways were analyzed through the MetaboAnalyst online website.Results The learning and memory abilities of AD model rats were significantly decreased compared with the control group,and the levels of oxidative stress and lipid peroxides were significantly increased(P<0.05),while the SOD content was decreased considerably(P<0.01).The learning and memory abilities of AD model rats were improved,oxidative stress and lipid peroxidation levels were reversed,and serum SOD content was increased significantly after the intervention of PLR-AR,with better effects than single drugs.Through metabolomics,70 differential metabolites were identified between the AD model group and the control group,mainly involving 10 pathways,including phenylalanine,tyrosine,and tryptophan biosynthesis,phenylalanine metabolism,and unsaturated fatty acid biosynthesis,et.al.The intervention of PLR-AR could adjust 47 metabolites,with 20 metabolites showing significant differences(P<0.05).The significantly adjusted metabolites involve 6 pathways,including phenylalanine,tyrosine,and tryptophan biosynthesis,et al.Conclusion The combination of PLR and AR could significantly improve the learning and memory abilities of AD rat models.The mechanism may be related to the improvement of oxidative stress and lipid peroxidation levels,the increase of serum SOD content,and the regulation of phenylalanine,tyrosine,and tryptophan biosynthesis pathways.
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