Hu Jun, Yang Fengmin, Yang Guang, Pan Juhua, Tan Yumeng, Tang Yalin, Liu Yongmei, Zhang Hong, Wang Jie
Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
National Laboratory for Molecular Sciences, Center for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
Front Pharmacol. 2024 Jul 29;15:1361284. doi: 10.3389/fphar.2024.1361284. eCollection 2024.
Aging is characterized by a decline in the adaptability and resistance of the body. In this study, Bushen Kangshuai Granules (BKG), as a kind of Chinese herbal formula, was developed and shown to alleviate aging-related symptoms. Self-controlled study combined with RNA-seq and metabonomics were used to expound the efficacy and safety of BKG and revealed the regulation mechanism of BKG treating aging. experiments were used to confirm the analytical results. The aging cell model of AC16 cells were treated with D-galactose. The RT-qPCR was used to detect the impact of BKG on telomere length. The DCFH-DA staining was used for detecting intracellular ROS. The targeted signaling pathway was selected and verified using Western blot. After 8 weeks of treatment, BKG significantly reduced SOD level ( 0.046), TCM aging symptoms ( 0.001) and TNF-α level ( 0.044) in the elderly participants. High-throughput sequencing showed that BKG reversed the expression of 70 and 79 age-related genes and metabolites, respectively. Further enrichment analysis indicated that BKG downregulated the - signaling pathway, extracellular matrix (ECM)-receptor interaction, and Rap1 signaling pathway, while up-regulating sphingolipid metabolism. The results of experiments show that, after D-gal treatment, the viability and telomere length of AC16 cells significantly decreased ( 0.05), while the expression of ROS increased ( 0.05), BKG significantly increased the telomere length of AC16 cells and reduced the level of ROS expression ( 0.05). In addition, BKG decreased the expression of THBS1, PDGFRA, and EPS8L1( 0.05), consistent with the RNA-seq results. Our results also showed that BKG affects - signaling pathway. BKG can significantly improve aging-related symptoms and increase SOD levels, which may be associated with the reversal of the expression of various aging-related genes. The - signaling pathway and sphingolipid metabolism may be potential mechanisms underlying BKG anti-aging effects.
衰老的特征是身体的适应性和抵抗力下降。在本研究中，补肾抗衰颗粒（BKG）作为一种中药配方被研发出来，并显示出可缓解与衰老相关的症状。采用自身对照研究结合RNA测序和代谢组学来阐述BKG的疗效和安全性，并揭示BKG治疗衰老的调控机制。通过实验来证实分析结果。用D-半乳糖处理AC16细胞的衰老细胞模型。采用RT-qPCR检测BKG对端粒长度的影响。用DCFH-DA染色检测细胞内活性氧。使用蛋白质免疫印迹法选择并验证靶向信号通路。治疗8周后，BKG显著降低了老年参与者的超氧化物歧化酶水平（P<0.046）、中医衰老症状（P<0.001）和肿瘤坏死因子-α水平（P<0.044）。高通量测序表明，BKG分别逆转了70个和79个与年龄相关的基因及代谢物的表达。进一步的富集分析表明，BKG下调了PI3K-Akt信号通路、细胞外基质（ECM）-受体相互作用和Rap1信号通路，同时上调了鞘脂代谢。实验结果表明，D-半乳糖处理后，AC16细胞的活力和端粒长度显著降低（P<0.05），而活性氧的表达增加（P<0.05），BKG显著增加了AC16细胞的端粒长度并降低了活性氧表达水平（P<0.05）。此外，BKG降低了血小板反应蛋白1（THBS1）、血小板衍生生长因子受体α（PDGFRA）和表皮生长因子受体途径底物8样蛋白1（EPS8L1）的表达（P<0.05），与RNA测序结果一致。我们的结果还表明，BKG影响PI3K-Akt信号通路。BKG可显著改善与衰老相关的症状并提高超氧化物歧化酶水平，这可能与各种衰老相关基因表达的逆转有关。PI3K-Akt信号通路和鞘脂代谢可能是BKG抗衰老作用的潜在机制。
