GLSP ameliorates monocrotaline-induced pulmonary arterial hypertension through inhibition of the PI3K/AKT and MAPK signaling pathways.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling and right heart dysfunction, driven largely by excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs). The PI3K/AKT and MAPK signaling pathways are key regulators of this aberrant proliferation. This study investigated whether Ganoderma lucidum spore powder (GLSP), a traditional Chinese medicine with cardiovascular protective effects, ameliorates PAH through modulation of these pathways. In vivo, GLSP administration to monocrotaline (MCT)-induced PAH rats significantly reduced mean pulmonary arterial pressure and right ventricular systolic pressure, attenuated pulmonary vascular wall thickening and fibrosis, and improved right ventricular function, accompanied by suppression of PI3K/AKT and MAPK phosphorylation. In vitro, GLSP reversed PDGFBB-induced PASMC proliferation, migration, and activation of PI3K/AKT and MAPK signaling. Network pharmacology and molecular docking further revealed that GLSP components stably bind to AKT1, SRC, PIK3CA, HSP90AA1, and ESR1-key nodes within these pathways. Our findings, from both in vivo and in vitro experiments, demonstrate that GLSP ameliorates MCT-induced PAH and pulmonary vascular remodeling by inhibiting aberrant PASMC proliferation and migration via suppression of the PI3K/AKT and MAPK signaling axes, highlighting GLSP as a promising therapeutic candidate for PAH.