Deciphering the angiogenic potential of Zhishi Xiebai Guizhi decoction in coronary heart disease: an in-depth network pharmacology and experimental investigation

Abstract ZXGD Decoction, a traditional Chinese formulation historically used for cardiovascular ailments, was evaluated for its efficacy in coronary heart disease (CHD) through an integrated network pharmacology and randomized controlled trial (RCT) approach. Its selection was rooted in documented t...

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Main Authors: Yingli Mo, Yuping Xu, Bei Lu, Xiaojuan Fan, Qingshuang Zhang, Shaowu Cheng, Qinghua Peng
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05379-1
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author Yingli Mo
Yuping Xu
Bei Lu
Xiaojuan Fan
Qingshuang Zhang
Shaowu Cheng
Qinghua Peng
author_facet Yingli Mo
Yuping Xu
Bei Lu
Xiaojuan Fan
Qingshuang Zhang
Shaowu Cheng
Qinghua Peng
author_sort Yingli Mo
collection DOAJ
description Abstract ZXGD Decoction, a traditional Chinese formulation historically used for cardiovascular ailments, was evaluated for its efficacy in coronary heart disease (CHD) through an integrated network pharmacology and randomized controlled trial (RCT) approach. Its selection was rooted in documented therapeutic benefits for blood stasis and endothelial dysfunction, with modern pharmacology identifying active compounds (e.g., luteolin, quercetin) targeting inflammation and oxidative stress pathways. Network analysis revealed ZXGD’s multi-target mechanism, prominently modulating the PI3K-AKT and NF-κB pathways, supported by robust molecular docking scores (binding affinity < -7.0 kcal/mol). These findings align with CHD pathophysiology, suggesting ZXGD disrupts critical inflammatory cascades. In a double-blind RCT (n = 180), ZXGD adjunct therapy significantly improved angina frequency (35% reduction vs. control, p < 0.01) and endothelial function (FMD increase: 2.8% ± 0.5 vs. 1.2% ± 0.4, p < 0.05) over 12 weeks, with no severe adverse events. This underscores ZXGD’s clinical potential as a safe complementary treatment. Notably, lipid profile enhancements (LDL-C reduction: 18.3% vs. 11.7%) correlated with predicted network targets, including LDLR and HMGCR. Our results bridge traditional use with mechanistic evidence, reinforcing ZXGD’s role in CHD management. While prior studies emphasize ZXGD’s anti-thrombotic effects, this work uniquely validates its anti-inflammatory and lipid-modulating properties, addressing gaps in understanding its systemic impact. Clinically, these findings advocate for ZXGD’s integration into CHD therapeutic protocols, particularly for patients with residual inflammatory risk.
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spelling doaj-art-0e8b2aea9c2249a5a75e98b76a12f9f82025-08-20T04:01:34ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-05379-1Deciphering the angiogenic potential of Zhishi Xiebai Guizhi decoction in coronary heart disease: an in-depth network pharmacology and experimental investigationYingli Mo0Yuping Xu1Bei Lu2Xiaojuan Fan3Qingshuang Zhang4Shaowu Cheng5Qinghua Peng6Yiyang Medical CollegeYiyang Medical CollegeHunan University of Chinese MedicineYiyang Medical CollegeHunan University of Chinese MedicineHunan University of Chinese MedicineHunan University of Chinese MedicineAbstract ZXGD Decoction, a traditional Chinese formulation historically used for cardiovascular ailments, was evaluated for its efficacy in coronary heart disease (CHD) through an integrated network pharmacology and randomized controlled trial (RCT) approach. Its selection was rooted in documented therapeutic benefits for blood stasis and endothelial dysfunction, with modern pharmacology identifying active compounds (e.g., luteolin, quercetin) targeting inflammation and oxidative stress pathways. Network analysis revealed ZXGD’s multi-target mechanism, prominently modulating the PI3K-AKT and NF-κB pathways, supported by robust molecular docking scores (binding affinity < -7.0 kcal/mol). These findings align with CHD pathophysiology, suggesting ZXGD disrupts critical inflammatory cascades. In a double-blind RCT (n = 180), ZXGD adjunct therapy significantly improved angina frequency (35% reduction vs. control, p < 0.01) and endothelial function (FMD increase: 2.8% ± 0.5 vs. 1.2% ± 0.4, p < 0.05) over 12 weeks, with no severe adverse events. This underscores ZXGD’s clinical potential as a safe complementary treatment. Notably, lipid profile enhancements (LDL-C reduction: 18.3% vs. 11.7%) correlated with predicted network targets, including LDLR and HMGCR. Our results bridge traditional use with mechanistic evidence, reinforcing ZXGD’s role in CHD management. While prior studies emphasize ZXGD’s anti-thrombotic effects, this work uniquely validates its anti-inflammatory and lipid-modulating properties, addressing gaps in understanding its systemic impact. Clinically, these findings advocate for ZXGD’s integration into CHD therapeutic protocols, particularly for patients with residual inflammatory risk.https://doi.org/10.1038/s41598-025-05379-1Network pharmacologyZhishi Xiebai Guizhi decoctionCoronary heart diseaseAngiogenesisTraditional Chinese medicineZebrafish
spellingShingle Yingli Mo
Yuping Xu
Bei Lu
Xiaojuan Fan
Qingshuang Zhang
Shaowu Cheng
Qinghua Peng
Deciphering the angiogenic potential of Zhishi Xiebai Guizhi decoction in coronary heart disease: an in-depth network pharmacology and experimental investigation
Scientific Reports
Network pharmacology
Zhishi Xiebai Guizhi decoction
Coronary heart disease
Angiogenesis
Traditional Chinese medicine
Zebrafish
title Deciphering the angiogenic potential of Zhishi Xiebai Guizhi decoction in coronary heart disease: an in-depth network pharmacology and experimental investigation
title_full Deciphering the angiogenic potential of Zhishi Xiebai Guizhi decoction in coronary heart disease: an in-depth network pharmacology and experimental investigation
title_fullStr Deciphering the angiogenic potential of Zhishi Xiebai Guizhi decoction in coronary heart disease: an in-depth network pharmacology and experimental investigation
title_full_unstemmed Deciphering the angiogenic potential of Zhishi Xiebai Guizhi decoction in coronary heart disease: an in-depth network pharmacology and experimental investigation
title_short Deciphering the angiogenic potential of Zhishi Xiebai Guizhi decoction in coronary heart disease: an in-depth network pharmacology and experimental investigation
title_sort deciphering the angiogenic potential of zhishi xiebai guizhi decoction in coronary heart disease an in depth network pharmacology and experimental investigation
topic Network pharmacology
Zhishi Xiebai Guizhi decoction
Coronary heart disease
Angiogenesis
Traditional Chinese medicine
Zebrafish
url https://doi.org/10.1038/s41598-025-05379-1
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