Shexiang Tongxin dropping pill improves homocysteine-induced coronary microvascular dysfunction via regulating PI3K/Akt/eNOS pathwayOA
Objective:To establish a mouse model of homocysteine(Hcy)-induced coronary microvascular dysfunction(CMD),and to evaluate the therapeutic efficacy of Shexiang Tongxin dropping pill(STDP)and elucidate its underlying mechanisms.Methods:The chemical composition and quality of STDP were characterized using ultra-high performance liquid chromatography,and its absorbed components were identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.CMD was induced in C57BL/6J mice by feeding a 3%methionine diet for four weeks.STDP efficacy was evaluated using laser speckle perfusion imaging,tomato lectin staining,and quantification of plasma nitric oxide(NO),reactive oxygen species(ROS),and endothelial adhesion molecules(intercellular cell adhesion molecule-1[ICAM-1],vascular cell adhesion molecule-1[VCAM-1]).Network pharmacology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify potential targets and regulatory pathways.An in vitro Hcy-induced endothelial injury model was used to validate the effects of STDP on cell viability,NO production,and activation of phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)pathway.Results:STDP was stable,with 180 constituents identified in the preparation and 30 absorbed components in plasma.STDP treatment restored perfusion,increased plasma NO,decreased ROS,and downregulated ICAM-1 and VCAM-1.Network analysis identified 152 putative targets,highlighting the PI3K/Akt pathway as the central,with PIK3CA,AKT1,and NOS3 as key nodes.In vitro,STDP enhanced cell viability,NO production,and PI3K/Akt/eNOS phosphorylation,these effects were abolished by pharmacological inhibition of PI3K and eNOS.Conclusion:A 3%methionine diet for four weeks effectively induces CMD in C57BL/6J mice.STDP,rich in bioactive components,alleviates Hcy-induced CMD by activating the PI3K/Akt/eNOS pathway,thereby improving endothelial function and microvascular perfusion.These findings support STDP as a promising therapeutic candidate for CMD management.
Shuai Li;Zuxian Zhang;Ming Gong;Xiaojun Li;Xuan Jia;Yijun Chen;Xianwen Tang;Wei Wang
National Key Laboratory of TCM Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,ChinaNational Key Laboratory of TCM Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,China Institute of Formula and Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,ChinaDepartment of Cardiology,Beijing University of Chinese Medicine Shenzhen Hospital(Longgang),Shenzhen 518000,ChinaNational Key Laboratory of TCM Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,China Institute of Formula and Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,China Basic Medical College,Gansu University of Chinese Medicine,Lanzhou 730000,ChinaNational Key Laboratory of TCM Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,China Institute of Formula and Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,ChinaNational Key Laboratory of TCM Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,China Institute of Formula and Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,ChinaDepartment of Cardiology,Beijing University of Chinese Medicine Shenzhen Hospital(Longgang),Shenzhen 518000,ChinaNational Key Laboratory of TCM Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,China Institute of Formula and Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510000,China
医药卫生
Shexiang Tongxin dropping pillHomocysteineCoronary microvascular dysfunctionEndothelial dysfunctionPI3K/Akt/eNOS pathway
《Journal of Traditional Chinese Medical Sciences》 2026 (1)
P.77-89,13
supported by the National Key Research and Development Program of China(2022YFC3500100)the National Natural Science Foundation of China(82230126 and U24A20800)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2023ZD0502600)National Science Fund for Excellent Young Scholars(82222075)the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory(Project HQL2024PZ045 and HQCML).
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