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 μM) and XMA (250 μg/mL) for 48 h. Sprague–Dawley rats were randomly grouped into eight groups (n = 8 per group): (I) control group received saline; (II) MCT group received MCT (60 mg/kg); (III) SIL-Low group received MCT + SIL at 10 mg/kg/day; (IV) SIL-high group received MCT + SIL at 30 mg/kg/day; (V) XMA-High group received MCT + XMA at 251.6 mg/kg/day; (VI) SIL (Low)+XMA (Low) group received SIL (10 mg/kg) + XMA at 62.9 mg/kg/day; (VII) SIL (Low)+XMA (Medium) group received SIL (10 mg/kg) + XMA at 125.8 mg/kg/day; (VIII) SIL (Low)+XMA (High) group received SIL (10 mg/kg) + 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 μg/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.

Keywords:

• Pulmonary artery pressure
• oxidative stress
• inflammation
• combination treatment

Author contributions

Yaolu Zhu, Binya Sun, and Guofeng Li designed the experimental scheme and prepared the manuscript. Yaolu Zhu, Yabin Sun, Shichang Zhang, Yiwei Zhao and Boxin Zhao carried out the experiment. Yaolu Zhu, Yabin Sun and Chuyuan Li analyzed the data and wrote the manuscript. All the authors approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant from Pearl River S&T Nova Program of Guangzhou [20180601006].