Abstract：
BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) has become a significant health and economic burden globally. Yinchenhao decoction (YCHD) is a traditional Chinese medicine formula that has been validated to exert therapeutic effects on NAFLD.
OBJECTIVE: The current study aimed to explore the pharmacological mechanisms of YCHD on NAFLD and further identify the potential active compounds acting on the main targets.
METHODS: Compounds in YCHD were screened and collected from TCMSP and published studies, and their corresponding targets were obtained from the SWISS and SEA databases. NAFLD-related targets were searched in the GeneCards and DisGeNet databases. The \"compound- intersection target\" network was constructed to recognize the key compounds. Moreover, a PPI network was constructed to identify potential targets. GO and KEGG analyses were performed to enrich the functional information of the intersection targets. Then, molecular docking was used to identify the most promising compounds and targets. Finally, molecular dynamics (MD) simulations were performed to verify the binding affinity of the most potential compounds with the key targets.
RESULTS: A total of 53 compounds and 556 corresponding drug targets were collected. Moreover, 2684 NAFLD-related targets were obtained, and 201 intersection targets were identified. Biological processes, including the apoptotic process, inflammatory response, xenobiotic metabolic process, and regulation of MAP kinase activity, were closely related to the treatment of NAFLD. Metabolic pathways, non-alcoholic fatty liver disease, the MAPK signaling pathway, and the PI3K-Akt signaling pathway were found to be the key pathways. Molecular docking showed that quercetin and isorhamnetin were the potential active compounds, while AKT1, IL1B, and PPARG were the most promising targets. MD simulations further verified that the binding of PPARG-isorhamnetin (-35.96 ± 1.64 kcal/mol) and AKT1-quercetin (-31.47 ± 1.49 kcal/mol) was due to their lowest binding free energy.
CONCLUSIONS: This study demonstrated that YCHD exerts therapeutic effects for the treatment of NAFLD through multiple targets and pathways, providing a theoretical basis for further pharmacological research on the potential mechanisms of YCHD in NAFLD.
OBJECTIVE: The current study aimed to explore the pharmacological mechanisms of YCHD on NAFLD and further identify the potential active compounds acting on the main targets.
METHODS: Compounds in YCHD were screened and collected from TCMSP and published studies, and their corresponding targets were obtained from the SWISS and SEA databases. NAFLD-related targets were searched in the GeneCards and DisGeNet databases. The \"compound- intersection target\" network was constructed to recognize the key compounds. Moreover, a PPI network was constructed to identify potential targets. GO and KEGG analyses were performed to enrich the functional information of the intersection targets. Then, molecular docking was used to identify the most promising compounds and targets. Finally, molecular dynamics (MD) simulations were performed to verify the binding affinity of the most potential compounds with the key targets.
RESULTS: A total of 53 compounds and 556 corresponding drug targets were collected. Moreover, 2684 NAFLD-related targets were obtained, and 201 intersection targets were identified. Biological processes, including the apoptotic process, inflammatory response, xenobiotic metabolic process, and regulation of MAP kinase activity, were closely related to the treatment of NAFLD. Metabolic pathways, non-alcoholic fatty liver disease, the MAPK signaling pathway, and the PI3K-Akt signaling pathway were found to be the key pathways. Molecular docking showed that quercetin and isorhamnetin were the potential active compounds, while AKT1, IL1B, and PPARG were the most promising targets. MD simulations further verified that the binding of PPARG-isorhamnetin (-35.96 ± 1.64 kcal/mol) and AKT1-quercetin (-31.47 ± 1.49 kcal/mol) was due to their lowest binding free energy.
CONCLUSIONS: This study demonstrated that YCHD exerts therapeutic effects for the treatment of NAFLD through multiple targets and pathways, providing a theoretical basis for further pharmacological research on the potential mechanisms of YCHD in NAFLD.
摘要：
背景：非酒精性脂肪性肝病（NAFLD）已成为全球重大的健康和经济负担。茵陈蒿汤（YCHD）是一种已被验证对NAFLD具有治疗作用的中药配方。
目的：本研究旨在探讨YCHD对NAFLD的药理机制，并进一步确定潜在的主要作用靶点活性化合物。
方法：从TCMSP和已发表的研究中筛选和收集YCHD中的化合物，并从SWISS和SEA数据库中获得其相应的靶标。在GeneCards和DisGeNet数据库中搜索NAFLD相关靶标。构建了“复合交叉目标”网络来识别关键化合物。此外，构建PPI网络以识别潜在目标.进行GO和KEGG分析以丰富交叉靶标的功能信息。然后，分子对接用于识别最有前途的化合物和靶标。最后,进行分子动力学（MD）模拟以验证最有潜力的化合物与关键靶标的结合亲和力。
结果:共收集53个化合物和556个相应的药物靶标。此外，获得了2684个NAFLD相关目标，并确定了201个交叉目标。生物过程,包括凋亡过程，炎症反应，外源性生物代谢过程，和MAP激酶活性的调节，与NAFLD的治疗密切相关。代谢途径,非酒精性脂肪性肝病,MAPK信号通路，发现PI3K-Akt信号通路是关键通路。分子对接表明槲皮素和异鼠李素是潜在的活性化合物，而AKT1、IL1B、和PPARG是最有希望的目标。MD模拟进一步证实PPARG-异鼠李素(-35.96±1.64kcal/mol)和AKT1-槲皮素(-31.47±1.49kcal/mol)的结合是由于它们的最低结合自由能。
结论：本研究表明，YCHD通过多种靶点和途径发挥治疗NAFLD的疗效，为进一步研究YCHD在NAFLD中的潜在作用机制提供理论依据。
目的：本研究旨在探讨YCHD对NAFLD的药理机制，并进一步确定潜在的主要作用靶点活性化合物。
方法：从TCMSP和已发表的研究中筛选和收集YCHD中的化合物，并从SWISS和SEA数据库中获得其相应的靶标。在GeneCards和DisGeNet数据库中搜索NAFLD相关靶标。构建了“复合交叉目标”网络来识别关键化合物。此外，构建PPI网络以识别潜在目标.进行GO和KEGG分析以丰富交叉靶标的功能信息。然后，分子对接用于识别最有前途的化合物和靶标。最后,进行分子动力学（MD）模拟以验证最有潜力的化合物与关键靶标的结合亲和力。
结果:共收集53个化合物和556个相应的药物靶标。此外，获得了2684个NAFLD相关目标，并确定了201个交叉目标。生物过程,包括凋亡过程，炎症反应，外源性生物代谢过程，和MAP激酶活性的调节，与NAFLD的治疗密切相关。代谢途径,非酒精性脂肪性肝病,MAPK信号通路，发现PI3K-Akt信号通路是关键通路。分子对接表明槲皮素和异鼠李素是潜在的活性化合物，而AKT1、IL1B、和PPARG是最有希望的目标。MD模拟进一步证实PPARG-异鼠李素(-35.96±1.64kcal/mol)和AKT1-槲皮素(-31.47±1.49kcal/mol)的结合是由于它们的最低结合自由能。
结论：本研究表明，YCHD通过多种靶点和途径发挥治疗NAFLD的疗效，为进一步研究YCHD在NAFLD中的潜在作用机制提供理论依据。
