Tribulus terrestris L. confers protection against hypoxia induced pulmonary hypertension via regulation of HIF/ NF-κB signalling pathway

BACKGROUND: Pulmonary hypertension (PH) is a fatal cardiopulmonary disorder driven by hypoxia-induced vascular remodeling. The hypoxic pulmonary vasoconstriction (HPV) and increased pulmonary vascular resistance leads right ventricular failure and ultimately death. Limited therapies and poor prognosis demand novel interventions. Tribulus terrestris L., renowned for antioxidant and anti-inflammatory effects, may modulate various pathways of hypoxia induced pulmonary hypertension pathogenesis. OBJECTIVE: This study examines potential of T. terrestris to counter hypoxia-induced PH in a rodent model via HIF-NF-κB signalling. MATERIAL AND METHODS: Thirty male Wistar rats were randomly undertaken, 6 rats were utilized for standardization of drug dose (T. terrestris) and remaining 24 were divided into 4 groups with 6 animals in each group as normal control, pulmonary hypertension due to intermittent hypoxia, pulmonary hypertension due to intermittent hypoxia + Tadalafil drug, pulmonary hypertension due to intermittent hypoxia + T. terrestris 250 mg/kg. Right ventricular systolic pressure (RVSP), serum levels of reactive oxygen species (ROS), nitric oxide (NO),inducible nitric oxide synthase (iNOS) and inflammatory markers-hypoxia inducible factor-1α (HIF-1α), nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in all the groups were analysed. RESULTS: Administration of crude T. terrestris extract to hypoxic pulmonary hypertensive rats significantly reduced RVSP, ROS, NO, iNOS, and inflammatory markers. No significant difference in therapeutic outcomes was observed between T. terrestris and tadalafil treatment groups. CONCLUSION: T. terrestris exhibits biochemical and hemodynamic changes associated with marked improvement in pulmonary hypertension indicating strong anti-oxidative, anti-inflammatory, and anti-angiogenic effects. This is the first study to report the protective effects of T. terrestris against hypoxic pulmonary hypertension.