目的基于网络药理学探讨温胆汤对心力衰竭合并抑郁共病同治机制,并通过分子对接初步验证。方法通过TCMSP数据库与文献搜索得到温胆汤有效成分并预测作用靶点;在GeneCards、OMIM、DisGeNET以及TTD数据库搜索心力衰竭、抑郁症相关疾病靶点...目的基于网络药理学探讨温胆汤对心力衰竭合并抑郁共病同治机制,并通过分子对接初步验证。方法通过TCMSP数据库与文献搜索得到温胆汤有效成分并预测作用靶点;在GeneCards、OMIM、DisGeNET以及TTD数据库搜索心力衰竭、抑郁症相关疾病靶点,与温胆汤作用靶点取交集。通过STRING平台完成交集靶点的蛋白质相互作用网络的构建并预测核心靶点,并对交集靶点进行基因本体注释及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,最后利用分子对接验证核心成分及核心靶点的结合能力。结果温胆汤治疗心力衰竭合并抑郁的核心成分为木犀草素、川陈皮素、β-谷甾醇、黄芩苷、豆甾醇等,核心靶点主要包括肿瘤坏死因子、白细胞介素-6、蛋白激酶B1、白细胞介素-1β、肿瘤蛋白p53等,通过KEGG主要富集在晚期糖基化终产物及其受体、磷脂酰肌醇-3激酶/蛋白激酶B、环磷酸腺苷、丝裂原活化蛋白激酶等信号通路。分子对接结果表明,木犀草素等核心成分与肿瘤坏死因子、白细胞介素-6等核心靶点的结合活性较好。结论温胆汤可能通过抑制炎症反应及氧化应激反应、调节神经递质的释放等方面来治疗心力衰竭合并抑郁。展开更多
Objective:To explore the mechanism of Wendan Decoction(温胆汤)regulating leptin resistance in obesity by analyzing the level of leptin in peripheral blood,the expression of leptin receptor and signal pathway molecule ...Objective:To explore the mechanism of Wendan Decoction(温胆汤)regulating leptin resistance in obesity by analyzing the level of leptin in peripheral blood,the expression of leptin receptor and signal pathway molecule POMC in hypothalamus.To analyze the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet,and the influence of adjusting methylation of OB-R,POMC gene promoter about Wendan decoction.Methods:Model rats were randomly divided into model control group and drug observation group,additional normal rats with 8 rats in each group.The models were established by high fat diet.The observation group was treated with Wendan Decoction(温胆汤)and the other two groups were treated with sterilized drinking water once a day for 6 weeks.Body weight was recorded every week during the intervention.Peripheral blood and hypothalamus were collected at the end of the experiment.The serum leptin level was measured by ELISA method,and the expression of OB-R and POMC in hypothalamus was detected by RT-qPCR method.Methylation level of OB-R and POMC promoter detected by methylation specific PCR.Results:Our results revealed that Wendan Decoction(温胆汤)could effectively reduce body weight,the body weight in the drug observation group was significantly lower than that in the model control group,and the difference between the two groups was statistically significant.The level of leptin in peripheral blood and the expression of OB-R in hypothalamus were consistent with the trend of body weight.The heavier the weight,the higher the level of leptin and OB-R.Wendan Decoction(温胆汤)could reduce the level of leptin and OB-R in peripheral blood while reducing body weight.Compared with the model control group,the difference was statistically significant.The heavier the weight,the lower the level of POMC expression.Wendan Decoction(温胆汤)could increase the expression of POMC while reducing body weight,which had statistical significance compared with the model control group.The methylation status of OB-R and POMC promoter in hypothalamus was not significantly associated with obesity induced by high fat diet,and Wendan Decoction(温胆汤)had no effect on methylation status.Conclusions:Wendan Decoction(温胆汤)could inhibit obesity by affecting the expression of leptin receptor and POMC mRNA in hypothalamus to a large degree.There was no obvious change about the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet.And it was not related to the change of methylation status of gene promoter about the mechanism of Wendan Decoction(温胆汤).展开更多
文摘目的基于网络药理学探讨温胆汤对心力衰竭合并抑郁共病同治机制,并通过分子对接初步验证。方法通过TCMSP数据库与文献搜索得到温胆汤有效成分并预测作用靶点;在GeneCards、OMIM、DisGeNET以及TTD数据库搜索心力衰竭、抑郁症相关疾病靶点,与温胆汤作用靶点取交集。通过STRING平台完成交集靶点的蛋白质相互作用网络的构建并预测核心靶点,并对交集靶点进行基因本体注释及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,最后利用分子对接验证核心成分及核心靶点的结合能力。结果温胆汤治疗心力衰竭合并抑郁的核心成分为木犀草素、川陈皮素、β-谷甾醇、黄芩苷、豆甾醇等,核心靶点主要包括肿瘤坏死因子、白细胞介素-6、蛋白激酶B1、白细胞介素-1β、肿瘤蛋白p53等,通过KEGG主要富集在晚期糖基化终产物及其受体、磷脂酰肌醇-3激酶/蛋白激酶B、环磷酸腺苷、丝裂原活化蛋白激酶等信号通路。分子对接结果表明,木犀草素等核心成分与肿瘤坏死因子、白细胞介素-6等核心靶点的结合活性较好。结论温胆汤可能通过抑制炎症反应及氧化应激反应、调节神经递质的释放等方面来治疗心力衰竭合并抑郁。
基金National Natural Science Foundation of China(No.81302907,81960851)Science and Technology Research Project of Jiangxi Education Department(GJJ160830)Jiangxi Provincial Natural Science(No.20171BAB205080)。
文摘Objective:To explore the mechanism of Wendan Decoction(温胆汤)regulating leptin resistance in obesity by analyzing the level of leptin in peripheral blood,the expression of leptin receptor and signal pathway molecule POMC in hypothalamus.To analyze the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet,and the influence of adjusting methylation of OB-R,POMC gene promoter about Wendan decoction.Methods:Model rats were randomly divided into model control group and drug observation group,additional normal rats with 8 rats in each group.The models were established by high fat diet.The observation group was treated with Wendan Decoction(温胆汤)and the other two groups were treated with sterilized drinking water once a day for 6 weeks.Body weight was recorded every week during the intervention.Peripheral blood and hypothalamus were collected at the end of the experiment.The serum leptin level was measured by ELISA method,and the expression of OB-R and POMC in hypothalamus was detected by RT-qPCR method.Methylation level of OB-R and POMC promoter detected by methylation specific PCR.Results:Our results revealed that Wendan Decoction(温胆汤)could effectively reduce body weight,the body weight in the drug observation group was significantly lower than that in the model control group,and the difference between the two groups was statistically significant.The level of leptin in peripheral blood and the expression of OB-R in hypothalamus were consistent with the trend of body weight.The heavier the weight,the higher the level of leptin and OB-R.Wendan Decoction(温胆汤)could reduce the level of leptin and OB-R in peripheral blood while reducing body weight.Compared with the model control group,the difference was statistically significant.The heavier the weight,the lower the level of POMC expression.Wendan Decoction(温胆汤)could increase the expression of POMC while reducing body weight,which had statistical significance compared with the model control group.The methylation status of OB-R and POMC promoter in hypothalamus was not significantly associated with obesity induced by high fat diet,and Wendan Decoction(温胆汤)had no effect on methylation status.Conclusions:Wendan Decoction(温胆汤)could inhibit obesity by affecting the expression of leptin receptor and POMC mRNA in hypothalamus to a large degree.There was no obvious change about the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet.And it was not related to the change of methylation status of gene promoter about the mechanism of Wendan Decoction(温胆汤).
