Bioactive compound combinations from Rhodiola tangutica alleviate pulmonary vascular remodeling in high-altitude pulmonary hypertension rats through the PI3K–AKT pathway
Abstract
Background Hypoxia-induced pulmonary vascular remodeling is central to the development of high-altitude pulmonary hypertension (HAPH). Rhodiola tangutica has traditionally been used to prevent chronic mountain sickness. Although its active fraction (ACRT) shows therapeutic potential for HAPH, the main pharmacodynamic substances remain unclear due to its complex composition. Aims This study aimed to identify bioactive equivalent combinatorial components (BECCs) of ACRT that alleviate pulmonary vascular remodeling in HAPH rats and explore the underlying pharmacological mechanisms. Methods Seventy adult Sprague–Dawley rats were divided into control, hypoxia, hypoxia + ACRT (150 mg/kg), hypoxia + BECCs (25, 50, and 100 mg/kg), and hypoxia + sildenafil (30 mg/kg) groups. An HAPH rat model was induced using a hypobaric hypoxia chamber simulating an altitude of 5,000 m. The effects of BECCs on pulmonary vascular remodeling in HAPH rats were evaluated based on hemodynamic indexes and histopathological changes, alongside antioxidant properties. Phosphoproteomics and Western blotting were performed to analyze AKT1-related protein expression in lung tissues. In vitro, 3% O2-induced pulmonary artery smooth muscle cell (PASMC) models were used to evaluate the anti-proliferative effects of BECCs and identify the dominant components. The underlying mechanisms were explored using Western blotting and a drug affinity responsive target stability (DARTS) assay to assess binding affinity.…
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