Investigation of the Mechanism of Mongolian Medicine Wulan Shisanwei Tang (十三味乌兰汤) on Rats with Essential Hypertension Based on Network Pharmacology and Animal Experiments

Author：SUN Buer1, CHEN Xiuhong2, ZHOU Shuangbao3, BAI Chunlin1

Unit：1.Inner Mongolia Medical University, Hohhot Inner Mongolia 010110, China; 2.Inner Mongolia Clinical Medical College, Inner Mongolia Medical University/Inner Mongolia Autonomous Region People's Hospital, Hohhot Inner Mongolia 010010, China; 3.Hohhot Hospital of Traditional Chinese Medicine and Mongolian Medicine, Hohhot Inner Mongolia 010020, China

Quote：引用：孙布尔，陈秀红，周双宝，白春林.基于网络药理和动物实验探讨蒙药十三味乌兰汤对原发性高血压大鼠的作用机制[J].中医药导报,2026,32(4):55-66.

DOI：10.13862/j.cn43-1446/r.2026.04.010

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Abstract：

Objective: To investigate the mechanism of Mongolian medicine Wulan Shisanwei Tang (WLSSWT) on essential hypertension (EH) rats by network pharmacology, molecular docking technology, and animal experiments. Methods: Utilizing the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Chinese Herbal Medicine Database (HERB), and related literature, the active components and their target sites of WLSSWT were identified. The online Mendelian Human Genetics Database (OMIM), GeneCards, DrugBank, and the Target to Drug (TTD) database were employed to search for EH-related target sites, and the intersection of the two was constructed to form an "active component-target" network diagram. Proteinprotein interaction (PPI) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Gene Ontology (GO) enrichment analysis were performed on the shared target sites between WLSSWT and EH. Molecular docking between active components and key targets was completed using AutodockTools 1.5.6 software. Visualization was achieved with PyMOLWin 2.4.0 software. A total of 60 rats were randomly divided into blank group, model group, WLSSWT low dose (0.27 g/kg) group, WLSSWT medium dose (0.54  g/kg) group, WLSSWT high dose (1.08 g/kg) group, and Valsartan (28.8 mg/kg) group, 10 rats in each. Except for the blank group, essential hypertension rat model was established in remaining groups by continuous intragastric administration of N-nitro-L-arginine methyl ester hydrochloride (L-NAME) solution. After successful modeling, the blank group and the model group were given an equal amount of normal saline, while the remaining groups were treated with WLSSWT and valsartan, respectively, for a treatment period of 4 weeks. Blood pressure in rats was observed, and HE staining was performed to examine pathological changes in myocardial cells. Western blotting was used to detect the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in myocardial tissue. Enzyme linked immunosorbent assay (ELISA) was employed to measure the levels of endothelin-1 (ET-1) and nitric oxide (NO) in serum. Results: The active components of WLSSWT include epigallocatechin gallate, quercetin, gallic acid, kaempferol, and luteolin. A total of 362 intersecting targets were identified, with key targets involving phosphatidylinositol 3-kinase regulatory subunit 1 (PIK3R1), mitogen-activated protein kinase 1 (MAPK1), epidermal growth factor receptor (EGFR), estrogen receptor 1 (ESR1), serine/threonine kinase 1 (Akt1), heat shock protein 90α family member 1A (HSP90AA1), cyclin-dependent kinase 4 (CDK-4), cyclin-dependent kinase 2 (CDK-2), cyclin-dependent kinase inhibitor 1A (CDKN1A), receptor tyrosine kinase 2 (ERBB2), cyclin D1 (CCND1), cyclin A2 (CCNA2), tumor protein p53 (TP53), sarcoma virus oncogene (SRC), BCL2-like protein 1 (BCL2L1), and conserved helical-loop-helical ubiquitous kinase (CHUK). Molecular docking results demonstrated high binding affinity between the core active components and key targets. Animal experiments showed that after modeling, blood pressure in the WLSSWT group, Valsartan group, and model group rats was significantly higher than that in the blank group (P<0.01), while after administration, blood pressure in the WLSSWT group and Valsartan group rats was significantly lower than that in the model group (P<0.01). Compared with the blank group, the model group exhibited moderate structural abnormalities in myocardial tissue, with irregular arrangement of myocardial fibers, increased interstitial spaces in some myocardial fibers, mild interstitial congestion, and minimal inflammatory cell infiltration. Serum NO levels were significantly reduced in model group (P<0.01), while ET-1 levels were significantly elevated (P<0.01), and the expression of Akt/PI3K in myocardial tissue was significantly increased in model group (P<0.01). Compared with the model group, the WLSSWT group and the Valsartan group showed significant improvement in the aforementioned cardiac structural abnormalities, with markedly elevated serum NO levels (P<0.01), significantly reduced ET-1 levels, and significantly decreased Akt/PI3K expression in myocardial tissue (P<0.01). Conclusion: WLSSWT may alleviate high-salt-induced hypertension and myocardial hypertrophy by regulating the PI3K/Akt signaling pathway. When exerting its effects on EH, WLSSWT demonstrates a multi-component, multi-target, and multi-pathway synergistic characteristic.

Key words：essential hypertension; Wulan Shisanwei Tang; Mongolian medicine; mechanism of action; network pharmacology; molecular docking; rat

摘要：

目的：采用网络药理学、分子对接技术和动物实验，探讨蒙药十三味乌兰汤（Wulan Shisanwei Tang，WLSSWT）对原发性高血压（EH）大鼠的作用机制。方法：借助中药系统药理学数据库与分析平台（TCMSP）、中药数据库（HERB）及相关文献，检索WLSSWT的活性成分及其作用靶点，利用在线孟德尔遗传人类数据库（OMIM）、基因卡片数据库（GeneCards）、DrugBank数据库和治疗靶点数据库（TTD）检索EH的相关靶点并取两者交集，构建“活性成分-靶点”网络图，对WLSSWT与EH共有靶点进行蛋白质-蛋白质相互作用（PPI）分析、京都基因与基因组百科全书（KEGG）富集分析及基因本体（GO）富集分析；运用AutodockTools 1.5.6软件完成活性成分同关键靶点的分子对接；利用PyMOLWin 2.4.0软件实现相关可视化。将60只SD大鼠随机分为空白组、模型组、WLSSWT低剂量（0.27 g/kg）组、WLSSWT中剂量（0.54 g/kg）组、WLSSWT高剂量（1.08 g/kg）组、缬沙坦（28.8 mg/kg）组，每组各10只；除空白组外，其余组采用N-硝基-L-精氨酸甲酯盐酸盐（L-NAME）溶液持续灌胃的方式建立高血压模型大鼠；造模成功后，空白组和模型组给予等量的生理盐水，其余组分别予以WLSSWT及缬沙坦治疗，治疗周期为4周；观察大鼠血压，苏木精-伊红（HE）染色观察心肌细胞的病理变化，蛋白质印迹（Western blotting）法检测心肌组织磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）蛋白表达，酶联免疫吸附试验（ELISA）检测血清中内皮素-1（ET-1）、一氧化氮（NO）含量。结果：WLSSWT的有效成分为表没食子儿茶素没食子酸酯、槲皮素、虫胶酸、山柰酚、木犀草素等；研究共获得362个交集靶点，关键靶点涉及PI3K调节亚基1（PIK3R1）、丝裂原活化蛋白激酶1（MAPK1）、表皮生长因子受体（EGFR）、雌激素受体1（ESR1）、丝氨酸/苏氨酸激酶1（Akt1）、热休克蛋白90α家族A类成员1（HSP90AA1）、细胞周期蛋白依赖性激酶4（CDK-4）、细胞周期蛋白依赖性激酶2（CDK-2）、细胞周期蛋白依赖性激酶抑制因子1A（CDKN1A）、受体酪氨酸蛋白激酶2（ERBB2）、细胞周期蛋白D1（CCND1）、细胞周期蛋白A2（CCNA2）、肿瘤蛋白p53（TP53）、肉瘤病毒癌基因（SRC）、BCL2样蛋白1（BCL2L1）、保守螺旋环螺旋广泛存在激酶（CHUK）等；分子对接结果表明核心活性成分和关键靶点之间具有较高的结合亲和力。动物实验结果显示，造模后WLSSWT各组、缬沙坦组及模型组大鼠血压明显高于空白组（P<0.01)，给药后WLSSWT各组、缬沙坦组大鼠血压明显低于模型组（P<0.01）。与空白组比较，模型组大鼠心肌组织整体结构中度异常，组织心肌纤维排列不规则，可见部分心肌纤维间隙增大，组织间质可见轻微淤血，组织可见少量炎症细胞浸润；模型组大鼠血清NO水平显著降低（P＜0.01），ET-1水平显著升高（P＜0.01），心肌组织Akt、PI3K表达量显著升高（P＜0.01）。与模型组比较，WLSSWT各组、缬沙坦组大鼠显著改善上述心脏结构异常，血清NO水平明显升高（P＜0.01），ET-1水平明显降低，心肌组织Akt、PI3K表达量明显降低（P＜0.01）。结论：WLSSWT可能通过调控PI3K/Akt信号通路缓解高盐诱导的高血压及心肌肥厚，WLSSWT对EH发挥作用时，呈现出多成分、多靶点及多途径协同的特性。

关键词：原发性高血压；十三味乌兰汤；蒙药；作用机制；网络药理学；分子对接；大鼠

Release time：2026-04-26

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