Therapeutic Effects of Active Compounds from Poria Cocos on Pulmonary Hypertension

Chronic inflammation plays a crucial role in the development and progression of pulmonary hypertension, leading to vascular remodeling, elevated pulmonary arterial pressure, and ultimately right heart failure. The limited long-term efficacy of vasodilator-based therapies highlights the urgent need for novel anti-inflammatory treatment strategies. Poria cocos, a medicinal fungus widely used in traditional Chinese medicine, exhibits diverse pharmacological activities, including anti-inflammatory, antioxidant, and antifibrotic effects. However, its therapeutic potential in pulmonary hypertension remains insufficiently elucidated. In this study, an integrative strategy combining network pharmacology, molecular docking, and both in vitro and in vivo validation was employed to explore the potential protective mechanisms of Poria cocos against pulmonary hypertension. Network analysis identified 105 common targets linking the active constituents of Poria cocos to pulmonary hypertension-related pathways. Molecular docking simulations further demonstrated that key bioactive compounds─7,9(11)-dehydropachymic acid, Eburicoic acid, and Cerevisterol─exhibited strong binding affinities toward IL-6 and TNFα, two pivotal inflammatory mediators involved in vascular remodeling and chronic inflammation in pulmonary hypertension. These findings were further supported by in vitro experiments showing significant downregulation of IL-6 and TNFα expression following treatment with the identified compounds. Importantly, in vivo studies using a hypoxia-induced pulmonary hypertension mouse model demonstrated that these active ingredients significantly reduced RVSP, alleviated right ventricular hypertrophy, attenuated pulmonary vascular remodeling, and suppressed circulating IL-6 and TNFα levels, thereby improving pulmonary hemodynamics and inflammatory status. Collectively, these results provide mechanistic insights into the multitarget therapeutic potential of Poria cocos and establish a scientific basis for its further development as a promising alternative strategy for pulmonary hypertension treatment.