The mechanism and material basis of Tibetan medicine Tsantan Sumtang in the relaxation of pulmonary arterioles based on TCMIP and experimental verification

PAN Xu; WANG Yi-wen; BAI Hai-jun; LU Dian-xiang; LI Zhan-qiang; YANG Zhan-ting

doi:10.20251/j.cnki.1003-3734.2025.15.012

Abstract：Objective:To explore the material basis and mechanism of action of Tsantan Sumtang,a Tibetan medicine(TS),in relaxation of pulmonary arterioles.Methods:TCMIP database was used to analyze the active ingredients of the formulation and the disease targets.And the interaction between active components in TS and HAPH disease targets was elucidated by constructing the prescription-disease-target interaction network,and the multi-dimensional network diagram of"prescription-Chinese herbal medicine-component-disease-target-pathway"of TS-HAPH was also established.Molecular docking was used to verify the interaction between target drugs and core targets in the multi-dimensional network diagram.The vasodilatory activity of the active components of TS on pulmonary vessels was evaluated using an isolated vascular ring experiment.To establish a hypoxia-induced proliferation model of PASMCs,the concentration of intracellular Ca2+was measured by laser confocal microscopy.ELISA assay was used to analyze the effects of active components of TS on cGMP and cAMP levels.Results:Through the construction of the multidimensional network of"prescription-herbal medicine-component-core target-pathway-disease",we found that 19 active components from the 3 herbs in TS acted on 136 targets,participating in the regulation of 22 signaling pathways,closely related to the treatment of HAPH.Molecular docking results showed that the core components of TS had strong binding ability to the core targets.The top three components with binding energy are Naringenin,Ellagic acid,and Daucosterol.The in vitro vascular ring experiments were conducted using these three monomers.The results showed that Naringenin,Ellagic Acid and Daucosterol had a vasodilatory effect on the pre-constricted pulmonary arterioles vascular rings of rats.The vasodilation rate was(71.55±3.17)％,(68.91±17.72)％and(75.08±4.35)％.After pretreatment with the NOS inhibitor L-NAME and the cyclooxygenase inhibitor INDO,the vasodilatory effects of Naringenin,Ellagic acid,and Daucosterol on NE precontraction were significantly attenuated.Pretreatment with Gli reduced the vasorelaxant effects of Naringenin,Ellagic acid,and Daucosterol.Intervention with the Kv channel inhibitor 4-AP reduced the vasodilator effect of Naringenin and Daucosterol on NE precontraction.Pretreatment with KIR channel inhibitor BaCl2 significantly reduced the vasodilator effects of Ellagic acid and Daucosterol.Treatment with TEA only reduced the vasodilator effect of Daucosterol.The results of cell experiments showed that Daucosterol could significantly reduce the Ca2+concentration in hypoxia-induced PASMCs.It significantly increased the levels of cGMP and cAMP.Conclusion:TS can inhibit hypoxia-induced proliferation and vasodilation of PASMCs by regulating cGMP-PKG signaling pathway and activating Kv channel in PASMCs.