Baicalin attenuates pulmonary hypertension by targeting AMPK/CPT1A-mediated fatty acid metabolism

Pulmonary hypertension (PH) is a life-threatening cardiopulmonary vascular disease, characterized by vascular remodeling due to the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Baicalin has shown therapeutic potential for PH. However, its underlying mechanism remains unclear.

The aim is to investigate the therapeutic potential and underlying mechanism of baicalin against PH.

Both in vivo and in vitro models of PH were employed. The in vivo model was established using Su5416 combined with hypoxia (SuHx), while the in vitro model involved hypoxia-induced PASMCs.

We first evaluated the pharmacological effect of baicalin on disease progression using physiological and biochemical assessments. We then employed a comprehensive suite of techniques to elucidate its mechanisms of action, including transthoracic echocardiography, immunofluorescence, immunohistochemistry, flow cytometry, Western blot, molecular docking, surface plasmon resonance (SPR), network pharmacology, and transcriptomic analyses.

Baicalin treatment improved hemodynamic parameters and attenuated pulmonary vascular remodeling, right ventricular systolic pressure (RVSP), and right ventricular hypertrophy in SuHx-induced PH mice. It also inhibited hypoxia-induced proliferation and migration of PASMCs in vitro. Network pharmacology and transcriptomic analyses identified baicalin as a modulator of metabolic pathways, particularly fatty acids oxidation (FAO), with CPT1A as a key regulator. Baicalin inhibited AMPK phosphorylation and CPT1A expression, thereby reducing FAO activity and ATP production. Molecular docking and SPR studies confirmed strong binding between baicalin and AMPKα1, supporting its direct regulatory role.

This study demonstrates that baicalin alleviates PH by modulating FAO through inhibition of the AMPK/CPT1A axis. Our findings provide evidence for the therapeutic efficacy of baicalin and elucidate its molecular mechanism, suggesting a promising therapeutic intervention for PH.