AUTHOR=Hu Jun , Yang Fengmin , Yang Guang , Pan Juhua , Tan Yumeng , Tang Yalin , Liu Yongmei , Zhang Hong , Wang Jie 

TITLE=Integrating transcriptomics and metabolomics to reveal the protective effect and mechanism of Bushen Kangshuai Granules on the elderly people

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1361284

DOI=10.3389/fphar.2024.1361284

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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. <italic>In vitro</italic> 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.</p><p><bold>Results:</bold> After 8 weeks of treatment, BKG significantly reduced SOD level (<italic>p =</italic> 0.046), TCM aging symptoms (<italic>p &lt;</italic> 0.001) and TNF-α level (<italic>p =</italic> 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 <italic>PI3K</italic>-<italic>AKT</italic> signaling pathway, extracellular matrix (ECM)-receptor interaction, and Rap1 signaling pathway, while up-regulating sphingolipid metabolism. The results of <italic>in vitro</italic> experiments show that, after D-gal treatment, the viability and telomere length of AC16 cells significantly decreased (<italic>p &lt;</italic> 0.05), while the expression of ROS increased (<italic>p &lt;</italic> 0.05), BKG significantly increased the telomere length of AC16 cells and reduced the level of ROS expression (<italic>p &lt;</italic> 0.05). In addition, BKG decreased the expression of THBS1, PDGFRA, and EPS8L1(<italic>p &lt;</italic> 0.05), consistent with the RNA-seq results. Our results also showed that BKG affects <italic>PI3K</italic>-<italic>AKT</italic> signaling pathway.</p><p><bold>Conclusion:</bold> 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 <italic>PI3K</italic>-<italic>AKT</italic> signaling pathway and sphingolipid metabolism may be potential mechanisms underlying BKG anti-aging effects.</p>