基于网络药理学策略探讨四君子汤治疗癌性恶病质的潜在机制

Potential mechanism of Sijunzi decoction in the treatment of cancer cachexia using the network pharmacology analysis

目的基于网络药理学方法探讨四君子汤治疗癌性恶病质的可能机制。方法本研究采用一个全面的网络药理学策略,由四个顺序模块组成:靶点预测、网络构建、分子对接、GO和KEGG富集分析。结果四君子汤中的7,9(11)-dehydropachymic acid和Taraxerol化合物可能通过作用于INS,PCK2,FABP3,eIF4E,SKP1,CCND1,CTNNB1,STAT5A,IL6ST,AR,CYCS,VEGFA等靶点来调节PI3K-Akt信号通路和Wnt信号通路,发挥调节代谢和抑制肿瘤的作用,最终达到治疗癌性恶病质的目的。结论四君子汤通过多个化合物、多个靶点、多个通路的直接或间接协同作用,能够有效地治疗癌性恶病质。

Objective Cancer cachexia is a multifactorial syndrome characterized by anorexia, weight loss, and muscle atrophy that not only affects treatment effectiveness, but also reduces the quality of life and survival of patients. The Sijunzi Decoction(SJZD) is a representative prescription in traditional Chinese medicine(TCM) to strengthen the spleen and replenish the Qi and used to improve the cachexia symptoms of cancer patients. This study explored the underlying molecular mechanism of SJZD anti-cancer cachexia activity. Methods A comprehensive network pharmacology strategy consisting of four sequential modules(the target prediction, network construction, molecular docking, GO and KEGG enrichment analysis)was performed to analyze the core gene targets and pathways. Results The compounds of 7,9(11)-dehydropachymic acid and Taraxerol in SJZD were able to regulate the PI3 K-Akt and Wnt signaling pathways by targeting INS, PCK2, FABP3, eIF4 E, SKP1, CCND1, CTNNB1,STAT5 A, IL6 ST, AR, CYCS, VEGFA. The SJZD could regulate the body metabolism and inhibit tumor inhibition;thus, to improve the cachexia symptoms of cancer patients. Conclusion SJZD effectively improves the cachexia symptoms of cancer patients through the direct or indirect synergy of multiple compounds and multiple gene targets and pathways.