BackgroundAging is a pressing global concern and is frequently accompanied by the emergence of many chronic diseases. Xiyangshen Sanqi Danshen granules (XSD) have antioxidant, anti-inflammatory and anti-fatigue functions, but the mechanism of their anti-aging effects is not clear. MethodsThis study elucidated the anti-aging mechanism and potentially active ingredients of XSD by performing transcriptomic analysis and network pharmacological analysis in a D-galactose (D-gal)-induced C57BL/6J mouse aging model. ResultsXSD improved learning and memory abilities while enhanced motor function in D-gal-induced aging mice, as shown by Morris water maze, passive avoidance test, and rotating rod test results. Additionally, XSD significantly increased the vascular pulse wave velocity (PWV), β-stiffness index and pressure strain elastic coefficient (EP), decreased carotid distensibility (CD) and decreased the expression levels of P53 and 8-OHdG in the common carotid arteries of D-gal mice. Transcriptome sequencing analysis identified that the AMPK/SIRT1 signaling pathway is the potential mechanism by which XSD attenuates aging. XSD also increased the protein levels of Ki67, AMPK, SIRT1 and the nuclear translocation of Nrf2 while decreased the protein levels of P21, P53, IL-18, 8-OHdG, nitrotyrosine, and COX-2 and the nuclear translocation of NF-κB p65 in the brains of D-gal-induced mice. The administration of the AMPK inhibitor and SIRT1 inhibitor hindered the anti-aging effect of XSD, as indicated by an elevation of 8-OHdG, COX-2, and nuclear translocation of NF-κB p65 ; and a decrease of Ki67 and the nuclear translocation of Nrf2. Network pharmacological analysis revealed that the potential active ingredients of XSD were quercetin, kaempferol, tanshinone IIA, isorhamnetin, ginsenoside F2, and cryptotanshinone. ConclusionCollectively, XSD mitigated D-gal-induced aging in C57BL/6J mice through enhancing the AMPK/SIRT1 signaling pathway. This research provides potential drugs for anti-aging and also promotes the usage of the anti-aging effect of XSD.
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