Xinmai 'an extract enhances the efficacy of sildenafil in the treatment of pulmonary arterial hypertension via inhibiting MAPK signalling pathway

Abstract

Context: Xinmai 'an tablet has been used to improve myocardial blood supply. Recently, some compounds from its formula have shown that they can treat pulmonary arterial hypertension (PAH). Objective: This study investigates the effects of Xinmai 'an extract (XMA) on PAH and further tests the co-therapeutic enhancement with sildenafil (SIL). Materials and methods: Pulmonary artery smooth muscle cells were subjected to stimulation with SIL (12.5 lM) and XMA (250 lg/mL) for 48 h. Sprague-Dawley rats were randomly grouped into eight groups (n ¼ 8 per group): (I) control group received saline; (II) MCT group received MCT (60 mg/kg); (III) SIL-Low group received MCT þ SIL at 10 mg/kg/day; (IV) SIL-high group received MCT þ SIL at 30 mg/kg/day; (V) XMA-High group received MCT þ XMA at 251.6 mg/kg/day; (VI) SIL (Low)þXMA (Low) group received SIL (10 mg/kg) þ XMA at 62.9 mg/kg/day; (VII) SIL (Low)þXMA (Medium) group received SIL (10 mg/kg) þ XMA at 125.8 mg/kg/day; (VIII) SIL (Low)þXMA (High) group received SIL (10 mg/kg) þ XMA at 251.6 mg/ kg/day. Both XMA and SIL were given by gavage and were maintained daily for 2 weeks. Results: XMA could improve SIL's efficacy in the treatment of PAH by decreasing cell viability more effectively at non-cytotoxic concentrations (250 lg/mL) and reducing Right Ventricular Systolic Pressure (RVSP) in PAH rat. Potential mechanisms might at least in part be through activating the MAPK signalling pathway. Discussion and conclusions: The combination of XMA and SIL can improve the efficacy of pulmonary hypertension and reduce the dosage of SIL.