Rules of Syndrome and Treatment of Unstable Angina Pectoris Guided by Vessel-collateral Theory and Mechanism Analysis Based on Network Pharmacology / 中国实验方剂学杂志

ABSTRACT

Objective:Guided by nutrient-defense stages in the vessel-collateral theory， the modern medical cases of unstable angina pectoris（UAP） were systematically collated and analyzed to explore the rules of syndrome and treatment of UAP and the molecular mechanism of core Chinese herbal combination in the treatment of UAP based on network pharmacology. Method:All medical cases with UAP treated by Chinese medicinal compounds were retrieved from PubMed，China National Knowledge Infrastructure （CNKI），Wanfang Data， VIP， and SinoMed published between database inception and November 2020. The syndromes of medical cases were determined based on the nutrient-defense stages of the vessel-collateral theory. Rules of syndrome and treatment of UAP were investigated by data mining methods， such as frequency statistics， cluster analysis， and enhanced FP-Growth algorithm. The molecular mechanism of core Chinese herbal combination in the treatment of UAP was analyzed by network pharmacology. Result:The first four syndromes of UAP with high frequencies were deficiency and stagnation of collateral Qi， blood stasis obstructing collaterals， depression and stagnation of collateral Qi， and turbid phlegm obstructing collaterals. The Chinese herbal medicines with high frequencies included Salviae Miltiorrhizae Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， and Astragali Radix， which were effective in resolving stasis， dredging collaterals， replenishing Qi， consolidating defensive Qi， regulating Qi， relieving depression， and dispelling phlegm. The association analysis indicated that the core Chinese herbal combination in the treatment of UAP was Salviae Miltiorrhizae Radix Chuanxiong Rhizoma-Astragali Radix. Four Chinese herbal combinations were obtained by cluster analysis. As revealed by network pharmacology， the key components of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix in the treatment of UAP included quercetin， luteolin， and tanshinone Ⅱ_A， and the key targets included serine/threonine-protein kinase 1 （Akt1）， mitogen-activated protein kinase 1 （MAPK1）， Jun， interleukin （IL）-6， and MAPK8. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis showed that phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathway might serve as the main pathway for its therapeutic efficacy. Conclusion:The basic pathogenesis of UAP is deficiency/depression and stagnation of collateral qi and turbid phlegm obstructing collaterals. The treatment should follow the principles of replenishing Qi， resolving stasis， and dredging collaterals， assisted with regulating Qi and resolving phlegm. The therapeutic efficacy of Salviae Miltiorrhizae Radix-Chuanxiong Rhizoma-Astragali Radix was achieved via multi-component， multi-target， and multi-pathway. This study is expected to inspire future UAP-related studies at the molecular level based on vessel-collateral theory.