Chen Jiye, Zhang Yongjian, Wang Yongcheng, Jiang Ping, Zhou Guofeng, Li Zhaoyu, Yang Jinlong, Li Xiao
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.
Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, China.
Chin Med. 2021 Apr 27;16(1):34. doi: 10.1186/s13020-021-00446-x.
Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation.
The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension.
A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C-C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1β, MMP-2 and MMP-9 in rats.
The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.
桂枝汤（GZD）是一种经典的中药方剂，已被广泛用于治疗高血压，但其潜在机制仍不清楚。本研究旨在通过整合网络药理学和实验验证来探索GZD治疗高血压的潜在机制和疗效。
从中药系统药理学数据库和分析平台（TCMSP）收集活性成分和相应靶点。从CTD、GeneCards、OMIM和Drugbank数据库中鉴定与高血压相关的靶点。构建多个网络以识别GZD抗高血压的关键化合物、核心靶点以及主要生物学过程和途径。使用Surflex-Dock软件验证关键靶点与其相应活性化合物之间的结合亲和力。采用Dahl盐敏感大鼠模型评估GZD对高血压的治疗效果。
共获得112种活性成分、GZD的222个靶点和341个高血压相关靶点。此外，鉴定出56个重叠靶点，其中5个被确定为用于实验验证的核心靶点，包括白细胞介素6（IL-6）、C-C基序趋化因子2（CCL2）、IL-1β、基质金属蛋白酶2（MMP-2）和MMP-9。通路富集分析结果表明，56个重叠靶点主要富集在肿瘤坏死因子（TNF）信号通路、Toll样受体（TLR）信号通路和核因子κB（NF-κB）信号通路等多种炎症通路中。分子对接证实，GZD的大多数活性化合物可与关键靶点紧密结合。实验研究表明，给予GZD可改善血压，减少心脏纤维化面积，并抑制大鼠IL-6、CCL2、IL-1β、MMP-2和MMP-9的表达。
GZD治疗高血压的潜在机制和疗效可能归因于对心脏炎症和纤维化的调节。
