Huangqi Shengmai Decoction alleviates right ventricular hypertrophy in hypoxic pulmonary hypertension via the Src/ERK1/2 signaling pathway.

Hypoxic pulmonary hypertension (HPH) often leads to right ventricular hypertrophy (RVH), a condition with limited therapeutic options. This study investigated the protective effects and mechanisms of Huangqi Shengmai Decoction (HSD) against HPH-induced RVH via network pharmacology combined with experimental validation. A total of 25 bioactive constituents in HSD were identified by HPLC-Q-Orbitrap-MS, and network pharmacology predicted the Src/ERK1/2 axis as a potential core signaling pathway. Further molecular docking validation confirmed that the key active ingredients of HSD, including Daidzein, Cryptotanshinone, and Andrographolide, showed favorable binding activities toward Src and ERK1/2. In a rat model of HPH (4-week hypoxia), HSD treatment significantly lowered right ventricular systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP), while attenuating RVH and collagen deposition. Mechanistically, HSD reduced oxidative stress, suppressed inflammation, and inhibited apoptosis, which was associated with the downregulation of p-Src and p-ERK1/2. In vitro studies using hypoxic H9c2 cardiomyocytes corroborated these findings. Notably, the administration of a Src activator abolished the protective effects of HSD, reversing the inhibition of the Src/ERK1/2 pathway and restoring hypertrophy and apoptosis. Collectively, the present study demonstrated that HSD ameliorates HPH-induced RVH by blocking the aberrant activation of the Src/ERK1/2 signaling cascade, thereby mitigating oxidative stress, inflammation, and cardiomyocyte apoptosis.