Aloe-emodin ameliorates experimental pulmonary arterial hypertension by modulating the PPARγ signaling pathway

Pulmonary arterial hypertension (PAH) is a serious cardiopulmonary vascular disease primarily caused by the abnormal proliferation and migration of pulmonary artery smooth muscle cells and is strongly linked to inflammation and oxidative stress. Aloe-emodin (AE), a natural compound derived from plants, exhibits pharmacological effects including anti-inflammatory and antioxidative properties, yet its protective role in PAH is not well understood. This study assessed the impact of AE on PAH in a monocrotaline-induced rat model and a platelet-derived growth factor-BB (PDGF-BB)-induced primary human pulmonary artery smooth muscle cells (HPASMCs) model. In the animal experiments, AE (low and high doses) or sildenafil (positive control) was administered via gavage for 28 days. The effects of AE on PAH were assessed by echocardiography, right heart catheterization, histopathological analysis, cell proliferation assays, scratch assays, and flow cytometry. Subsequently, peroxisome proliferator-activated receptor γ (PPARγ) expression and its associated downstream proteins were assessed. The study demonstrated that administration of AE at 100 mg/kg/day enhanced cardiac function, mitigated pulmonary vascular remodeling, and attenuated inflammation in PAH rats. Meanwhile, AE inhibited PDGF-BB-induced proliferation and migration of HPASMCs and promoted apoptosis. In PDGF-BB-stimulated HPASMCs, AE upregulated PPARγ expression, diminished the phosphorylation of NF-κB p65 and IκBα, activated the nuclear factor erythroid 2 related factor 2/heme oxygenase-1 signaling pathway, and suppressed inflammation and oxidative stress responses. However, GW9662 (a PPARγ inhibitor) attenuated the aforementioned effects of AE. Our findings suggest that AE alleviates PAH by upregulating the PPARγ signaling pathway. Thus, AE may provide a novel therapeutic strategy for PAH.