Exploring the mechanism of action of Maxing Xiongting mixture in the treatment of hypoxic pulmonary hypertension based on network pharmacology and molecular dynamics simulation

Hypoxic pulmonary hypertension (HPH) is a serious circulatory disease caused mainly by long-term chronic hypoxia-induced vasoconstriction and remodelling of the pulmonary arteries, with high morbidity and poor prognosis. Despite our understanding of the pathophysiology and treatment of HPH, there are currently no effective targeted drugs for this disease. Maxing Xiongting Mixture (MXXTM) is a commonly used herbal formula for the treatment of HPH. However, the specific components and molecular mechanisms of MXXTM for the treatment of HPH are unknown. The aim of this study was to explore the effects and potential mechanisms of MXXTM on HPH using network pharmacology, molecular docking and molecular dynamics (MD) simulations. The database search yielded 29 active compounds and 203 cross-targets, and identified quercetin, kaempferol, luteolin and isorhamnetin as key compounds. Protein-protein interaction (PPI) topology analysis identified AKT1, TNF, IL6, TP53, IL1B and PTGS2 as core targets. Enrichment analysis showed that the effects of MXXTM were mediated by inflammatory response, OS, vascular remodelling, apoptosis and value addition, and PI3K-Akt signalling pathway. In addition, molecular docking and ND simulations demonstrated good binding capacity between the compounds and the core targets. Among them, TP53-isorhamnetin had the lowest binding free energy (-94.341 KJ/mol). This study suggests that MXXTM may exert potential regulatory effects on HPH through a multi-component, multi-target, and multi-pathway approach. However, these conclusions require further validation through subsequent in vivo and in vitro studies.