Integrating “Pathway-Target-Active Ingredient” to Explore the Mechanism and Clinical Research of Shexiang Baoxin Pills in Treating Coronary Artery Lesions
Tan Liwu¹, Zhang Hongyu¹, Li Jinzen²,*
1Department of Cardiology I, Nanxishan Hospital, Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541002 2 Department of Internal Medicine I, Mengshan County People's Hospital, Mengshan, Guangxi 546700
Objective: To analyze the mechanism of Shexiang Baoxin Pills (SBP) against coronary artery lesions (CAL) via network pharmacology and validate it clinically. Methods: SBP components and targets were screened via TCMSP, TCMID, and Swiss Target Prediction. Intersecting with CAL targets from GeneGards formed a "drug‑ingredient‑target‑disease" network. STRING and DAVID supported PPI topology, GO annotation, and KEGG enrichment. A "pathway‑target‑ingredient" network clarified the formula's multi‑target, multi‑pathway synergy. Clinical efficacy, serum vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) levels, adverse reactions, and major adverse cardiovascular events (MACE) were compared among 240 patients with severe CAL, divided into control groups (no SBP) and experimental groups (SBP for 6 months). Results: Network pharmacology analysis identified 94 potential therapeutic targets of SBP for CAL. Core targets included tumor necrosis factor (TNF), interleukin 1 beta (IL1B), AKT serine/threonine kinase 1 (AKT1), insulin (INS), and RELA proto-oncogene, NF-kB subunit (RELA). Enriched pathways involved lipid metabolism and atherosclerosis. Clinical results showed that the total effective rates in all experimental groups were significantly higher than those in the control groups (P < 0.05). No statistically significant differences were observed in the adverse reactions or MACE between groups (P > 0.05). Serum levels of VEGF and Ang-1 were significantly elevated in all experimental groups compared to the control groups (P < 0.05). Conclusion: SBP exerts therapeutic effects through multi-component, multi-target, and multi-pathway actions, safely improving clinical outcomes in patients with CAL , with angiogenesis promotion as a key mechanism.
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Funding
This study was supported by Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine self-funded research projects(GZZC2020218).And Guangxi Zhuang Autonomous Region Health Commission self-funded research project(Z20200082)
References
Chen T, Yang Y (2024). Immunologic and inflammatory pathogenesis of chronic coronary syndromes: A review. Medicine (Baltimore), 103(44):e40354.
Dabeek WM, Marra MV (2019). Dietary Quercetin and Kaempferol: Bioavailability and Potential Cardiovascular-Related Bioactivity in Humans. Nutrients, 11(10):2288.
Di Pino A, DeFronzo RA (2019). Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents. Endocr Rev, 40(6):1447-1467.
Feng S, Dai Z, Liu AB, Huang J, Narsipur N, Guo G, Kong B, Reuhl K, Lu W, Luo Z, Yang CS (2018). Intake of stigmasterol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet. Biochim Biophys Acta Mol Cell Biol Lipids, 1863(10):1274-1284.
Huang J, Cai C, Zheng T, Wu X, Wang D, Zhang K, Xu B, Yan R, Gong H, Zhang J, Shi Y, Xu Z, Zhang X, Zhang X, Shang T, Zhou J, Guo X, Zeng C, Lai EY, Xiao C, Chen J, Wan S, Liu WH, Ke Y, Cheng H (2020). Endothelial Scaffolding Protein ENH (Enigma Homolog Protein) Promotes PHLPP2 (Pleckstrin Homology Domain and Leucine-Rich Repeat Protein Phosphatase 2)-Mediated Dephosphorylation of AKT1 and eNOS (Endothelial NO Synthase) Promoting Vascular Remodeling. Arterioscler Thromb Vasc Biol, 40(7):1705-1721.
Ha JM, Jin SY, Lee HS, Kum HJ, Vafaeinik F, Ha HK, Song SH, Kim CD, Bae SS (2022). Akt1-dependent expression of angiopoietin 1 and 2 in vascular smooth muscle cells leads to vascular stabilization. Exp Mol Med,54(8):1133-1145.
Jin Y, Yin X, Li Z, Xu J (2021). Mechanism of Baihe Decoction in the treatment of coronary heart disease based on network pharmacology and molecular docking. Ann Palliat Med, 10(3):3205-3218.
Kurano M, Hasegawa K, Kunimi M, Hara M, Yatomi Y, Teramoto T, Tsukamoto K (2018). Sitosterol prevents obesity-related chronic inflammation. Biochim Biophys Acta Mol Cell Biol Lipids, 1863(2):191-198.
Lu L, Sun X, Chen C, Qin Y, Guo X (2018). Shexiang Baoxin Pill, Derived From the Traditional Chinese Medicine, Provides Protective Roles Against Cardiovascular Diseases. Front Pharmacol, 9:1161.
Luo TT, Lu Y, Yan SK, Xiao X, Rong XL, Guo J (2020). Network Pharmacology in Research of Chinese Medicine Formula: Methodology, Application and Prospective. Chin J Integr Med, 26(1):72-80.
Li Y, Deng S, Liu B, Yan Y, Du J, Li Y, Jing X, Liu Y, Wang J, Du J, She Q (2021). The effects of lipid-lowering therapy on coronary plaque regression: a systematic review and meta-analysis. Sci Rep, 11(1):7999.
Li JJ, Wang CM, Wang YJ, Yang Q, Cai WY, Li YJ, Song M, Zang YL, Cui XH, Li Q, Chen Y, Weng XG, Zhu XX (2022). Network pharmacology analysis and experimental validation to explore the mechanism of Shenlian extract on myocardial ischemia. J Ethnopharmacol, 288:114973.
Melincovici CS, Boşca AB, Şuşman S, Mărginean M, Mihu C, Istrate M, Moldovan IM, Roman AL, Mihu CM (2018). Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis. Rom J Morphol Embryol, 2018;59(2):455-467.
Myszko M, Bychowski J, Skrzydlewska E, Łuczaj W (2025). The Dual Role of Oxidative Stress in Atherosclerosis and Coronary Artery Disease: Pathological Mechanisms and Diagnostic Potential. Antioxidants (Basel), 14(3):275.
Papadopoulos Z (2024). The role of the cytokine TNF-α in choroidal neovascularization: a systematic review. Eye (Lond), 38(1):25-32.
Su E, Yu P, Zhang B, Zhang A, Xie S, Zhang C, Li S, Zou Y, Liu M, Jiang H, Ge J (2020). Endothelial Intracellular ANG (Angiogenin) Protects Against Atherosclerosis by Decreasing Endoplasmic Reticulum Stress. Arterioscler Thromb Vasc Biol, 42(3):305-325.
Shen X, Zhao Z, Wang H, Guo Z, Hu B, Zhang G (2017). Elucidation of the Anti-Inflammatory Mechanisms of Bupleuri and Scutellariae Radix Using System Pharmacological Analyses. Mediators Inflamm, 2017:3709874.
van Loo G, Bertrand MJM (2023). Death by TNF: a road to inflammation. Nat Rev Immunol, 23(5):289-303.
Wei J, Dong B, Du X, Xu H (2023). Study of the mechanism of Shexiang Baoxin pill-mediated angiogenesis in acute myocardial infarction. Cardiovasc J Afr, 34:1-7.
Wei J, Ma T, Zhou C, Hao P, Li B, Wang X, Yu R, Zhu M, Wang Y (2022). Efficacy and safety of Shexiang Baoxin Pill for stable coronary artery disease: A systematic review and meta-analysis of 42 randomized controlled trials. Front Pharmacol, 13:1002713.
Yu Z, Li T, Zheng Z, Yang X, Guo X, Zhang X, Jiang H, Zhu L, Yang B, Wang Y, Luo J, Yang X, Tang T, Hu E (2025). Tailoring a traditional Chinese medicine prescription for complex diseases: A novel multi-targets-directed gradient weighting strategy. J Pharm Anal, 15(4):101199.
Yang Y, Gao S, Fang Q, Zhu M (2021). Efficacy and safety of Shexiang Baoxin Pill combined with Western medicine in the treatment of acute myocardial infarction: A single-center, double-blind, randomized controlled trial. Medicine (Baltimore), 100(3):e24246.
Zhang KJ, Zhu JZ, Bao XY, Zheng Q, Zheng GQ, Wang Y (2017). Shexiang Baoxin Pills for Coronary Heart Disease in Animal Models: Preclinical Evidence and Promoting Angiogenesis Mechanism. Front Pharmacol, 8:404.
Zhang J, Cui Q, Zhao Y, Guo R, Zhan C, Jiang P, Luan P, Zhang P, Wang F, Yang L, Yang X, Xu Y (2020). Mechanism of angiogenesis promotion with Shexiang Baoxin Pills by regulating function and signaling pathway of endothelial cells through macrophages. Atherosclerosis, 292: 99-111.
Zhang SD, Su ZH, Liu RH, Diao YY, Li SL, Ya PH, Li HL, Zhang WD (2018). Exploring the pathways and targets of Shexiang Baoxin Pill for coronary heart disease through a network pharmacology approach. World J Trad Chin Med, 4(4):137-146.
Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, Li X, Wang L, Wang L, Liu Y, Liu J, Zhang M, Qi J, Yu S, Afshin A, Gakidou E, Glenn S, Krish VS, Miller-Petrie MK, Mountjoy-Venning WC, Mullany EC, Redford SB, Liu H, Naghavi M, Hay SI, Wang L, Murray CJL, Liang X (2019). Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 394(10204):1145-1158.
