BACKGROUND Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese me...BACKGROUND Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM. AIM To investigate the protective mechanisms of JPQC decoction on UC based on systems pharmacology approach. METHODS We performed systems pharmacology to predict the active ingredients, the matched targets, and the potential pharmacological mechanism of JPQC on UC. In vivo, we explored the effects of JPQC in a colitis model induced by dextran sulfate sodium. In vitro, we adopted the bone marrow-derived macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the underlying mechanisms and effects of JPQC on UC under TNF-α stimulation. RESULTS Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC. Protein-protein interaction networks were established to identify the underlying therapeutic targets of JPQC on UC. Based on enrichment analyses, we proposed our hypothesis that JPQC might have a protective effect on UC via the NF-κB/HIF-1α signalling pathway. Subsequent experimental validation revealed that treatment with TNFα activated the NF-κB/HIF-1α signalling pathway in BMDMs, thereby damaging the epithelial barrier permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The findings were also confirmed in a dextran sulfate sodium-induced colitis model. CONCLUSION JPQC could improve the mucosal inflammatory response and intestinal epithelial barrier function via the NF-κB/HIF-1α signalling pathway, which provides new perspectives on the pharmaceutical development and clinical practice of TCM.展开更多
目的:研究大建中汤对大鼠脾阳虚证的治疗作用和潜在作用机制。方法:大鼠随机分成正常组,脾阳虚证模型组,附子理中丸阳性组和大建中汤低、中、高剂量组。除正常组外,其余各组采用“饮食失节+劳倦+苦寒泻下”法复制脾阳虚证大鼠模型,并给...目的:研究大建中汤对大鼠脾阳虚证的治疗作用和潜在作用机制。方法:大鼠随机分成正常组,脾阳虚证模型组,附子理中丸阳性组和大建中汤低、中、高剂量组。除正常组外,其余各组采用“饮食失节+劳倦+苦寒泻下”法复制脾阳虚证大鼠模型,并给予相应药物灌胃2周。检测各组大鼠体重、肛温、运动能力等指标,并对大鼠回肠和结肠组织病理变化进行检测。进一步提取回肠总RNA进行转录组测序,从而对差异基因进行GO和KEGG富集分析。结果:与模型组相比,大建中汤给药组大鼠体重、进食量、肛温以及脏器指数均明显升高( P <0.001),且运动能力接近正常组。大鼠回肠和结肠组织病理变化(以炎性浸润为主)得到改善,以低、中剂量效果较好。转录组测序结果显示,大鼠回肠组织的B细胞受体信号通路、NF-κB信号通路等免疫系统相关的信号通路明显上调。结论:大建中汤能明显改善脾阳虚证大鼠症状,其作用机制可能与提高机体免疫功能有关。展开更多
基金Supported by the National Natural Science Funds of China,No.81573892,No.81873253,and No.81704009
文摘BACKGROUND Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM. AIM To investigate the protective mechanisms of JPQC decoction on UC based on systems pharmacology approach. METHODS We performed systems pharmacology to predict the active ingredients, the matched targets, and the potential pharmacological mechanism of JPQC on UC. In vivo, we explored the effects of JPQC in a colitis model induced by dextran sulfate sodium. In vitro, we adopted the bone marrow-derived macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the underlying mechanisms and effects of JPQC on UC under TNF-α stimulation. RESULTS Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC. Protein-protein interaction networks were established to identify the underlying therapeutic targets of JPQC on UC. Based on enrichment analyses, we proposed our hypothesis that JPQC might have a protective effect on UC via the NF-κB/HIF-1α signalling pathway. Subsequent experimental validation revealed that treatment with TNFα activated the NF-κB/HIF-1α signalling pathway in BMDMs, thereby damaging the epithelial barrier permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The findings were also confirmed in a dextran sulfate sodium-induced colitis model. CONCLUSION JPQC could improve the mucosal inflammatory response and intestinal epithelial barrier function via the NF-κB/HIF-1α signalling pathway, which provides new perspectives on the pharmaceutical development and clinical practice of TCM.
文摘目的:研究大建中汤对大鼠脾阳虚证的治疗作用和潜在作用机制。方法:大鼠随机分成正常组,脾阳虚证模型组,附子理中丸阳性组和大建中汤低、中、高剂量组。除正常组外,其余各组采用“饮食失节+劳倦+苦寒泻下”法复制脾阳虚证大鼠模型,并给予相应药物灌胃2周。检测各组大鼠体重、肛温、运动能力等指标,并对大鼠回肠和结肠组织病理变化进行检测。进一步提取回肠总RNA进行转录组测序,从而对差异基因进行GO和KEGG富集分析。结果:与模型组相比,大建中汤给药组大鼠体重、进食量、肛温以及脏器指数均明显升高( P <0.001),且运动能力接近正常组。大鼠回肠和结肠组织病理变化(以炎性浸润为主)得到改善,以低、中剂量效果较好。转录组测序结果显示,大鼠回肠组织的B细胞受体信号通路、NF-κB信号通路等免疫系统相关的信号通路明显上调。结论:大建中汤能明显改善脾阳虚证大鼠症状,其作用机制可能与提高机体免疫功能有关。
