Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal Antihypertensive Effect of Gedan Jiangya Decoction

Abstract

Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD’s pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure.

Elucidating the anti-hypertensive mechanisms of Uncaria rhynchophylla-Alisma plantago-aquatica L: an integrated network pharmacology, cluster analysis, and molecular docking approach

“…Bioactive components of UR-AP were identified using the TCMSP (http://tcmspw.com/tcmsp.php) (Ru et al, 2014), TCMID (http://119.3.41.228:8000/tcmid/) (Huang et al, 2018), and DCABM-TCM (http://bionet.ncpsb.org.cn/dcabm-tcm/) (Liu et al, 2023). The ADME model, alongside published literature (Bai et al, 2021a;Bai et al, 2021b;Zhai et al, 2021;Liu et al, 2022), guided the setting of thresholds for oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18 to screen for bioactive components.…”

Unraveling the Therapeutic Mechanism of Saussurea involucrata against Rheumatoid Arthritis: A Network Pharmacology and Molecular Modeling-Based Investigation

“…In order to elucidate the relationships among target proteins and further refine key targets, the intersecting target genes were inputted into the STRING database (string-db.org, accessed on 17 May 2023) with a confidence level set at >0.9, and the species selected as H. sapiens (human) [37]. Based on this, the PPI network was constructed.…”

“…Information such as component-target, disease-target, drug-component, pathwaytarget, function-target, etc., were summarized and imported into Cytoscape for network visualization, to construct their relationship network. Then, network analysis was performed using the network analysis function [37], and according to the obtained degree, 10 components and 10 targets with a higher ranking were selected as core components and core targets.…”

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