Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling, inhibiting inflammatory response and oxidative stress, and inducing apoptosis

Background: Mufangji tang (MFJT) is composed of Ramulus Cinnamomi, Radix Ginseng, Cocculus orbiculatus (Linn.) DC., and Gypsum. In clinical settings, MFJT has been effectively employed in addressing a range of respiratory disorders, notably including pulmonary arterial hypertension (PAH). However, the mechanism of action of MFJT on PAH remains unknown. Methods: In this study, a monocrotaline-induced PAH rat model was established and treated with MFJT. The therapeutic effects of MFJT on PAH rat model were evaluated. Network pharmacology was conducted to screen the possible targets for MFJT on PAH, and the molecular docking between the main active components and the core targets was carried out. The key targets identified from network pharmacology were tested. Results: Results showed significant therapeutic effects of MFJT on PAH rat model. Analysis of network pharmacology revealed several potential targets related to apoptosis, inflammation, oxidative stress, and vascular remodeling. Molecular docking showed that the key components were well docked with the core targets. Further experimental validation results that MFJT treatment induced apoptosis (downregulated Bcl-2 levels and upregulated Bax levels in lung tissue), inhibited inflammatory response and oxdative stress (decreased the levels of IL-113, TNF-alpha, inducible NOS, and malondialdehyde, and increased the levels of endothelial nitric oxide synthase, nitric oxide, glutathione and superoxide dismutase), reduced the proliferation of pulmonary arterial smooth muscle cells (downregulated ET-1 and 13-catenin levels and ERK1/2 phosphorylation, increased GSK313 levels). Conclusion: Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis, inhibition of inflammation and oxidative stress, and the prevention of vascular remodeling.