活血解毒Ⅰ号方抗动脉粥样硬化的网络药理学分析及实验验证

doi:10.20047/j.issn1673-7210.2022.33.01

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Abstract Objective To explore the material basis and mechanism of Huoxue Jiedu Ⅰ Prescription in the treatment of atherosclerosis based on network pharmacology, and to carry out experimental verification. Methods The active ingredients and targets of Huoxue Jiedu Ⅰ Prescription were retrieved through the traditional Chinese medicine systems pharmacology database and analysis platform, and the information of protein targets was standardized by using Uniprot protein database. Target genes related to atherosclerosis were obtained from online Mendelian inheritance in man, GeneCards, and DrugBank databases, and common targets of drugs and diseases were screened. The “ingredient-target” network was constructed and key active components were screened. The STRING platform was used to construct the common target protein-protein interaction network and screen the key target genes. Matascape database was used for enrichment analysis of GO and KEGG pathways, and a multidimensional network diagram of “drug-target-pathway” was constructed. Thirty SPF 8-week-old male ApoE-/- mice, weighing 18-22 g, were fed with high-fat diet for 12 weeks to establish atherosclerosis model. They were divided into model group, statin group, and Huoxue Jiedu Ⅰ Prescription group according to the random number table method, with ten mice in each group. Ten male C57BL/6J mice of the same age and genetic background were selected as normal control group. Statin group was given 3.400 mg/(kg·d) of Atorvastatin, Huoxue Jiedu Ⅰ Prescription group was given 2.171 g/(kg·d) of drug liquid, normal control group and model group was given the same amount of normal saline. All the four groups were given gavage for 12 weeks. At the end of the experiment, colorimetric method was used to detect blood lipid indexes of the four groups, and HE staining and plaque proportion of aorta were quantitatively analyzed. The protein expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), caspase-3, and nuclear factor-κBp65 (NF-κBp65) in aortic tissues of the four groups were detected by Western blot. Results A total of 25 active ingredients of Huoxue Jiedu Ⅰ Prescription were screened, 214 potential targets were identified, and 118 targets were common with atherosclerotic diseases. GO analysis showed 2 173 results, including 165 pathways. The key active ingredients of Huoxue Jiedu Ⅰ Prescription in the treatment of atherosclerosis include quercetin, baicalin, β-sitosterol, ellagic acid, berberine, tetrandrine afrika, berberine, etc. It can regulate TNF, AKT1, IL-6, VEGFA, TP53, IL-1B, JUN, CASP3, PTGS2, PPARG, and other related targets. It may affect the occurrence and development of atherosclerosis through TNF, Toll-like receptor, NF-κB, HIF-1, PI3K-Akt, apoptosis, T-cell receptor, MAPK, Foxo, and other signaling pathways. The results of the experiment showed that serum total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) in the model group were higher than those in the normal control group, and the level of high density lipoprotein cholesterol in the model group was lower than that in the normal control group, serum TC, TG, and LDL-C in the Huoxue Jiedu Ⅰ Prescription group were lower than those in the model group, and the differences were statistically significant (P ＜ 0.05). The results of HE staining of aortic root showed that there was no atherosclerotic plaque deposition in the aortic root of the normal control group, and different degrees of atherosclerotic plaque deposition could be observed in the aortic root wall of the other three groups. Quantitative analysis of plaque proportion showed that the proportion of plaque area in the Huoxue Jiedu Ⅰ Prescription group was lower than that in the model group, and the difference was statistically significant (P ＜ 0.05). The protein levels of TNF-α, IL-6, caspase-3, and NF-κBp65 in the model group were higher than those in the normal control group, while those in the Huoxue Jiedu Ⅰ Prescription group were lower than those in the model group, and the differences were statistically significant (P ＜ 0.05). Conclusion This study preliminarily reveales the “multi-component, multi-target, multi-pathway” action network of Huoxue Jiedu Ⅰ Prescription in the treatment of atherosclerosis, and experimentally verifies that its mechanism of action is related to the inhibition of related inflammatory pathways and apoptosis, providing a research basis for the clinical application of Huoxue Jiedu Ⅰ Prescription in the treatment of atherosclerosis.

Key words： Huoxue Jiedu Ⅰ Prescription Atherosclerosis Network pharmacology Inflammation

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	TANG Ziwei GU Yimeng WU Yanyan YANG Lin XUE Mei

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TANG Ziwei GU Yimeng WU Yanyan YANG Lin XUE Mei. Network pharmacologic analysis and experimental verification of Huoxue Jiedu Ⅰ Prescription against atherosclerosis[J]. 中国医药导报, 2022, 19(33): 5-12,17.

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https://www.yiyaodaobao.com.cn/EN/10.20047/j.issn1673-7210.2022.33.01 OR https://www.yiyaodaobao.com.cn/EN/Y2022/V19/I33/5

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