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.
Zhongguo Zhong Yao Za Zhi. 2021 Jul;46(14):3465-3477. doi: 10.19540/j.cnki.cjcmm.20210309.401.
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 GSK3 B,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 and JAK-STAT signaling pathway,with PIK3 CB,PIK3 CA,CASP3,AKT1 and BCL2 as the key targets. These results suggested that WEMOL had anti hyperlipidemia effect,and its mechanism might be related to the protein expression regulation of lipid metabolism,nonalcoholic fatty liver disease and atherosclerosis related signaling pathways.
采用高脂饮食诱导的高脂血症仓鼠模型，探讨辣木叶水提取物（WEMOL）的降血脂作用。在此基础上，运用网络药理学预测其可能的作用机制。将金黄仓鼠随机分为正常饮食组（NFD）、高脂饮食组（HFD）、辛伐他汀组、WEMOL高剂量组（HIWEMOL）和WEMOL低剂量组（LOWEMOL）。各组同时给药66天，记录仓鼠体重变化。实验结束时，检测各组金黄仓鼠的血脂水平和血清转氨酶水平，并用苏木精-伊红（HE）染色观察肝脏病理变化。结果表明，WEMOL可显著降低血清总胆固醇（TC）、总甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-c）水平，减少肝脏组织脂质沉积，从而改善金黄仓鼠的高脂血症。根据网络药理学预测，分别得到辣木叶潜在活性成分的219个靶点和辣木叶水溶性潜在活性成分治疗高脂血症的185个靶点。对上述得到的219个靶点和185个靶点的PPI网络进行MCODE分析，分别得到5个和4个聚类。聚类的信号通路分析表明，在共同通路中，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信号通路与高脂血症相关。此外，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的代谢炎症，GSK3 B、F2、AKT1、RELA、SERPINE1可能是关键靶点。辣木叶水溶性潜在活性成分可通过调节AMPK信号通路和JAK-STAT信号通路调节脂质代谢，PIK3 CB、PIK3 CA、CASP3、AKT1和BCL2为关键靶点。这些结果提示，WEMOL具有降血脂作用，其机制可能与脂质代谢、非酒精性脂肪性肝病和动脉粥样硬化相关信号通路的蛋白表达调控有关。
