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| Exploration of the mechanism of Huazhuo Xingxue Decoction against hyperlipidemia based on network pharmacology |
| Hits 344 Download times 286 Received:May 24, 2023 |
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| DOI
10.11656/j.issn.1672-1519.2023.09.17 |
| Key Words
network pharmacology;Huazhuo Xingxue Decoction;hyperlipidemia;mechanism |
| Author Name | Affiliation | E-mail | | XI Jiaqiu | Shandong University of Traditional Chinese Medicine, Jian 250355, China | | | SHAO Yuze | Shandong University of Traditional Chinese Medicine, Jian 250355, China | | | WANG Zhonglin | Shandong University of Traditional Chinese Medicine, Jian 250355, China
Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jian 250355, China | wzl_jn@163.com |
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| Abstract
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| [Objective] To elucidate the mechanisms of Huazhuo Xingxue Decoction（HXD） against hyperlipidemia based on network pharmacology. [Methods] Rats model of hyperlipidemia was established by a high-fat diet for 8 weeks. The rats were divided into the control group，model group，high-dose group of HXD，medium-dose group of HXD，low-dose group of HXD and simvastatin group. After 8 weeks of intragastric administration，the weight，liver wet weight，liver index，serum TC，TG，LDL-C and HDL-C were measured. Pathomorphological changes in liver were observed by HE staining. The active ingredients and targets of HXD were retrieved from TCMSP and BATMAN-TCM. Related targets of hyperlipidemia were searched in Drugbank，DisGeNET，CTD，OMIM and GAD databases. Common targets of HXD and hyperlipidemia were extracted. Cytoscape 3.7.2 was used to set up the compound-target network. HXD-hyperlipidemia common target PPI network was established by using the STRING database and the topological parameters of PPI data were used to screen the hub targets. Then GO and KEGG enrichment analysis of common targets was carried out by David database. The mRNA expression were detected by RT-PCR. [Results] Compared with the control group，the liver index were higher（P＜0.05），liver steatosis were obvious，and serum TC，TG and LDL-C levels were significantly increased（P＜0.05）. Compared with the model group，the liver index were lower（P＜0.05），liver steatosis were attenuated significantly，and the serum TC，TG and LDL-C levels of rats in all groups of HXD were decreased（P＜0.05）；the HDL-C level increased in the high-dose group of HXD（P＜0.05）. Systems pharmacology revealed 327 targets for the 56 active ingredients of HXD and 112 candidate targets of hyperlipidemia. The 37 common targets of HXD and hyperlipidemia involved 37 active ingredients，such as crocetin，kaempferol，stigmasterol and physovenine. By screening，there were 15 hub targets were obtained，such as INS，ABCA1，PPARA，PPARG，ADIPOQ，APOA2. The enrichment analysis predicted that HXD had lipid-lowering effect mainly through PPAR，AMPK and PI3K/Akt signal pathway. AdipoR2，PPARα and APOA2 in PPAR signaling pathway were validated in PCR experiments. Compared with the control group，the mRNA expression of AdipoR2 and PPARα were down-regulated（P＜0.05） in the model group. Compared with the model group，the mRNA expression of AdipoR2 was up-regulated in the high-dose group of HXD（P＜0.05）；the mRNA expression of PPARα was up-regulated in the high-dose group and the medium-dose group of HXD（P＜0.05）；the mRNA expression of APOA2 was down-regulated in the high-dose group of HXD（P＜0.05）. [Conclusion] HXD can improve the disorder of lipid metabolism and reduce lipid deposition in hyperlipidemic rats，and its anti-hyperlipidemia mechanism may be related to the intervention of AdipoR2/ PPARα/APOA2 signaling pathway. |
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