Study on the molecular mechanisms of Liuwei Dihuang decoction against aging-related cognitive impairment based on network pharmacology and experimental verification

基于网络药理学和实验验证的六味地黄汤对抗衰老相关认知障碍的分子机制研究

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作者:Yin OuYang ,Bowei Chen ,Jian Yi ,Siqian Zhou ,Yingfei Liu ,Fengming Tian ,Fanzuo Zeng ,Lan Xiao ,Baiyan Liu

Abstract

Objective: Based on network pharmacology and experimental validation, this study aimed to screen the potential targets of Liuwei Dihuang decoction (LW) against mild cognitive impairment (MCI). Methods: Based on network pharmacology, this study preliminarily explored the targets and molecular mechanisms of LW in the treatment of MCI. The results showed that the mechanism of action of LW against MCI may be related to the cAMP pathway. Then, an aging cell and animal model was established to further verify its molecular mechanism. Results: A total of 23 active ingredients were identified in LW. In addition, through network pharmacological analysis, we found 22 anti-MCI active ingredients in LW, of which alisol B had the most significant effect, and predicted the potential mechanism pathway by which LW may improve MCI through the cAMP signaling pathway. Further in vivo and in vitro experiments confirmed that LW can alleviate cognitive dysfunction in aging mice and reduce D-galactose-induced senescent cells, which may be through activation of the cAMP/PKA/CREB signaling pathway. Conclusion: This study found that the traditional Chinese medicine formula LW may play a role in improving MCI by regulating the cAMP/PKA/CREB signaling pathway, which provides a reference for further clinical research on the anti-MCI effect of LW and its molecular mechanism. Keywords: Experimental validation; Liuwei Dihuang decoction; Mild cognitive impairment; Network pharmacology; UPLC-Q-TOF/MS.

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