Yin-chen Wu-ling powder alleviate cholestatic liver disease: Network pharmacological analysis and experimental validation.
Yin-chen Wu-ling powder alleviate cholestatic liver disease: Network pharmacological analysis and experimental validation.
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茵陈五苓散缓解胆汁淤积性肝病：网络药理分析与实验验证。
DOI：
10.1016/j.gene.2022.146973
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发表时间：
2022-10
期刊：
影响因子：
3.5
通讯作者：
Sun Xue-Hua
中科院分区：
文献类型：
--
作者：
You Li-Ping;Wang Kai-Xia;Lin Jia-Cheng;Ren Xiao-Yu;Wei Yu;Li Wen-Xuan;Gao Yue-Qiu;Kong Xiao-Ni;Sun Xue-Hua
茵陈五苓散对胆汁淤积性肝病具有潜在的治疗作用，但其有效成分及作用机制尚不清楚。研究方法：网络药理学和基因功能注释研究了YWP治疗CLD的多种活性成分、潜在靶点和可能机制。通过分子对接，验证了核心化合物的可靠性，包括关键基因和法尼醇X受体。最后，以Mdr 2-/-小鼠为实验动物，研究了YWP对CLD的治疗作用及其机制。结果如下：网络分析确定了9个主要活性成分，包括槲皮素、茵陈素、泽兰素、异鼠李素、毛蕊花素、芫花素、酿酒甾醇、大麻花苷元和谷甾醇。PPI网络预测涉及的10个枢纽基因是AKT 1、MAPK 1、MAPK 14、IL 6、RXRA、ESR 1、IL 10、NCOA 1、CAV 1和EGFR。KEGG和GO分析表明，YWP可能通过PI 3 K/Akt和MAKP信号来管理病理反应，例如炎症反应，从而有助于CLD治疗。分子对接结果显示，核心化合物与熊去氧胆酸（UDCA）和奥贝胆酸（OCA）在对AKT 1、MAPK 1、MAPK 14、RXRA和ESR的作用以及对FXR的亲和力方面具有相似的功能。此外，YWP还能显着减轻Mdr 2-/-小鼠的肝脏损伤并改善炎症反应。其机制探讨表明，YWP主要通过抑制AKT/P38 MAPK信号通路来减轻炎症反应。结论：本研究通过网络药理学分析和分子对接，首次揭示了养阴丸治疗慢性肝病的多种有效成分、潜在作用靶点和可能作用机制。YWP可通过抑制AKT/P38 MAPK信号通路，减轻炎症反应，从而减轻Mdr 2-/-小鼠胆汁淤积。
Yin-chen Wu-ling Powder (YWP) has potential therapeutic effects on cholestatic liver disease (CLD), however, its active compounds and conceivable mechanism are as yet indistinct. Methods: The network phar-macology and gene function annotation examined the multiple active ingredients, potential targets, and possible mechanisms of YWP in CLD treatment. Then the molecular docking reassured the reliability of the core com-pounds including the key genes and farnesoid X receptor (FXR). Finally, The Mdr2-/-mice were used to test the effect and mechanism of YWP against CLD. Results: The network analysis identified nine main active in-gredients, including quercetin, capillarisin, eupalitin, isorhamnetin, skrofulein, genkwanin, cerevisterol, geder-agenin, and sitosterol. The PPI network predicted the ten hub genes involved were AKT1, MAPK1, MAPK14, IL6, RXRA, ESR1, IL10, NCOA1, CAV1, and EGFR. The KEGG and GO analysis showed that YWP might contribute to CLD treatment through the PI3K/Akt and MAKP signalings to manage pathological reactions, for instance, in-flammatory responses. The molecular docking displayed a functional similarity among the core compounds with ursodeoxycholic acid (UDCA) and Obeticholic acid (OCA) on the effects on AKT1, MAPK1, MAPK14, RXRA, and ESR, and the affinity to FXR. In addition, the YWP could significantly attenuate hepatic injury and improve inflammatory response in Mdr2-/-mice. The mechanism exploration showed that YWP mainly decreased in-flammatory response by inhibiting AKT/P38MAPK signaling. Conclusion: This study firstly revealed the mul-tiple active ingredients, potential targets, and possible mechanism of YWP to treat CLD based on network pharmacology Analysis and molecular docking. YWP could alleviate cholestasis in Mdr2-/-mice by impairing inflammation via inhibiting AKT/P38MAPK Signaling.
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DOI：
10.1007/164_2019_227
发表时间：
2019-01-01
期刊：
BILE ACIDS AND THEIR RECEPTORS
影响因子：
--
作者：
Fiorucci, Stefano;Di Giorgio, Cristina;Distrutti, Eleonora
通讯作者：
Distrutti, Eleonora
影响因子：
--
作者：
Ye J;Li L;Hu Z
通讯作者：
Hu Z
影响因子：
1.7
作者：
Meng XY;Zhang HX;Mezei M;Cui M
通讯作者：
Cui M
影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
5.6
作者：
Yi YX;Ding Y;Zhang Y;Ma NH;Shi F;Kang P;Cai ZZ;Zhang T
通讯作者：
Zhang T