摘要
采用高脂饲料饲喂法诱导高脂血症金黄地鼠模型,探究辣木叶水提物抗高脂血症的药效,在此基础上,利用网络药理学预测其可能的作用机制。将金黄地鼠完全随机分为普通饲料饲喂组、高脂饲料饲喂组、辛伐他汀组及辣木叶水提物高、低剂量组,造模同时给药持续66 d,期间记录金黄地鼠体质量变化,实验结束后检测各组金黄地鼠血脂水平及血清转氨酶水平,苏木素-伊红(hematoxylin-eosin,HE)染色观察肝脏病理学变化。结果显示,辣木叶水提物能够显著降低金黄地鼠血清总胆固醇(total cholesterol,TC)、总甘油三酯(total triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoproteins cholesterol,LDL-c)水平,减轻肝脏组织中的脂质沉积,改善金黄地鼠高脂血症。通过网络药理学预测,分别获得219个辣木叶潜在活性成分治疗高脂血症及185个辣木叶水溶性潜在活性成分治疗高脂血症的靶点,对上述靶点的PPI网络进行MCODE模块分析,分别获得5个及4个功能模块,其信号通路分析结果显示,二者共有通路中,与高脂血症相关的信号通路有非酒精性脂肪肝、胰岛素抵抗、MAPK信号通路、雌激素信号通路、细胞凋亡和HIF-1信号通路等。除此之外,辣木叶潜在活性成分还可通过调节补体和凝血级联信号通路,抑制高脂血症代谢性炎症,GSK3B、F2、AKT1、RELA、SERPINE1可能为其关键靶点。辣木叶水溶性潜在活性成分还可通过调节AMPK信号通路及JAK-STAT信号通路,调节脂质代谢,PIK3CB、PIK3CA、CASP3、AKT1、BCL2可能为其关键靶点。以上结果表明,辣木叶水提物确有抗高脂血症药效,其机制可能与调节脂质代谢、非酒精性脂肪肝及动脉粥样硬化相关信号通路的蛋白表达有关。
High fat diet induced hyperlipidemia hamster model was used to explore the anti-hyperlipidemia effect of water extract of Moringa oleifera leaves(WEMOL).On this basis,the possible action mechanism was predicted by network pharmacology.Golden hamsters were randomly divided into normal diet group(NFD),high-fat diet group(HFD),simvastatin group,high dose group of WEMOL(HIWEMOL)and low dose group of WEMOL(LOWEMOL).The model was administered simultaneously for 66 days,during which the body weight changes of hamsters were recorded.At the end of the experiment,serum lipid level and serum transaminase level of golden hamsters in each group were detected,and the pathological changes of liver were observed by hematoxylin-eosin(HE)staining.The results showed that WEMOL could significantly decrease the serum total cholesterol(TC),total triglyceride(TG),low density lipoprotein cholesterol(LDL-c)levels,and reduce the lipid deposition in liver tissue,thus improving the hyperlipidemia of golden hamsters.According to the prediction of network pharmacology,219 targets of potential active components of M.oleifera leaves and 185 targets of water-soluble potential active components of M.oleifera leaves for the treatment of hyperlipidemia were obtained separately.The MCODE analysis was performed on the PPI network of 219 targets and 185 targets obtained above and got five and four clusters respectively.The signaling pathway analysis of clusters showed that among the common pathways,nonalcoholic fatty liver,insulin resistance,MAPK signaling pathway,estrogen signaling pathway,cell apoptosis and HIF-1 signaling pathway were associated with hyperlipidemia.In addition,the potential active components of M.oleifera leaves could also inhibit the metabolic inflammation of hyperlipidemia by modulating complement and coagulation cascades signaling pathway,and GSK3B,F2,AKT1,RELA,SERPINE1 might be the key targets.The water-soluble potential active components of M.oliefera leaves could modulate lipid metabolism by modulating AMPK signaling pathway
作者
沙子珺
黎彩凤
唐仕欢
杨洪军
张毅
李志勇
杨滨
SHA Zi-jun;LI Cai-feng;TANG Shi-huan;YANG Hong-jun;ZHANG Yi;LI Zhi-yong;YANG Bin(School of Pharmacy,Minzu University of China,Beijing 100081,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Academician Workstation of Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;National Resource Center for Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Collaborative Innovation Center for the Development of New Chinese Medicine Resources in Yunnan,Kunming 650051,China;Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming 650504,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2021年第14期3465-3477,共13页
China Journal of Chinese Materia Medica
基金
国家重点研发计划“中医药现代化研究”专项(2018YFC1706106)
云南省重大科技专项计划项目(2017ZF004)
国家“重大新药创制”科技重大专项(2018ZX10101001-005-003)。
关键词
辣木叶
高脂血症
网络药理学
降脂机制
Moringa oleifera leaves
hyperlipidemia
network pharmacology
lipid-lowering mechanism
