Yin Zhiru, Tian Liangliang, Kou Wenzhuo, Cao Guangzhao, Wang Liju, Xia Yufa, Lin Yidong, Tang Shihuan, Zhang Jingjing, Yang Hongjun
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang 330115, China.
Phytomedicine. 2025 Jan;136:156213. doi: 10.1016/j.phymed.2024.156213. Epub 2024 Nov 17.
Aging 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.
This 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.
XSD 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.
Collectively, 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.
衰老成为全球关注的紧迫问题，且常伴有多种慢性疾病的出现。西洋参三七丹参颗粒（XSD）具有抗氧化、抗炎和抗疲劳功能，但其抗衰老作用机制尚不清楚。
本研究通过在D - 半乳糖（D - gal）诱导的C57BL/6J小鼠衰老模型中进行转录组分析和网络药理学分析，阐明XSD的抗衰老机制和潜在活性成分。
如莫里斯水迷宫、被动回避试验和转棒试验结果所示，XSD改善了D - gal诱导的衰老小鼠的学习和记忆能力，同时增强了运动功能。此外，XSD显著增加了血管脉搏波速度（PWV）、β - 硬度指数和压力应变弹性系数（EP），降低了颈动脉扩张性（CD），并降低了D - gal小鼠颈总动脉中P53和8 - OHdG的表达水平。转录组测序分析确定AMPK/SIRT1信号通路是XSD延缓衰老的潜在机制。XSD还增加了D - gal诱导的小鼠大脑中Ki67、AMPK、SIRT1的蛋白水平以及Nrf2的核转位，同时降低了P21、P53、IL - 18、8 - OHdG、硝基酪氨酸和COX - 2的蛋白水平以及NF - κB p65的核转位。AMPK抑制剂和SIRT1抑制剂的给药阻碍了XSD的抗衰老作用，表现为8 - OHdG、COX - 2升高以及NF - κB p65核转位；Ki67和Nrf2核转位降低。网络药理学分析表明，XSD的潜在活性成分是槲皮素、山奈酚、丹参酮IIA、异鼠李素、人参皂苷F2和隐丹参酮。
总体而言，XSD通过增强AMPK/SIRT1信号通路减轻了D - gal诱导的C57BL/6J小鼠衰老。本研究为抗衰老提供了潜在药物，也促进了XSD抗衰老作用机制的研究。
