BACKGROUND: Hypoxia-induced pulmonary vascular remodeling is central to the development of high-altitude pulmonary hypertension (HAPH). 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. RESULTS: HAPH rat models were successfully established, as evidenced by changes in physiological parameters. BECCs showed comparable efficacy to ACRT in restoring hemodynamic indexes and histopathological changes. Mechanistically, BECCs modulated AKT phosphorylation and related protein expression. CONCLUSION: BECCs demonstrated comparable efficacy to ACRT in alleviating HAPH progression, reversing hypoxia-induced vascular remodeling, and inhibiting oxidative stress and PASMC proliferation by targeting the AKT protein. Flavonoids were identified as the key bioactive components contributing to the holistic effects of BECCs by regulating phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) pathways. These findings could be extended to improve quality control and clarify the bioactive components of