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Antihypertensive and renal protective effect of Shunaoxin pill combined with captopril on spontaneous hypertension rats - 14/03/20

Doi : 10.1016/j.biopha.2020.109977 
Shuli Man a, , Li Yang a , Hao Xiang a , Guanyu Lu b , Yijia Wang d , Changxiao Liu e , Wenyuan Gao c,
a State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China 
b State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China 
c Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China 
d Tianjin International School, 4-1 Sishui Rd, Hexi District, Tianjin, 300222, China 
e The State Key Laboratories of Pharmacodynamics and Pharmacokinetics, Tianjin, 300193, China 

Corresponding author at: College of Biotechnology, Tianjin University of Science & Technology, TEDA 13th street, Tianjin, 300457, China.College of BiotechnologyTianjin University of Science & TechnologyTEDA 13th streetTianjin300457China⁎⁎Corresponding author at: School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin, 300072, China.School of Pharmaceutical Science and TechnologyTianjin UniversityWeijin RoadTianjin300072China

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Abstract

Introduction

According to previous reports, hypertension has become the most common chronic disease in the world. Captopril, an angiotensin-converting enzyme inhibitor, has been widely used for the therapy of arterial hypertension and cardiovascular diseases therapy. Besides, Shunaoxin pill (SNX) as a traditional Chinese prescription showed antihypertensive effect in our previous research.

Objective

This study means to investigate whether SNX combining with captopril could show antihypertensive and renal protective effects on spontaneous hypertension rats (SHRs).

Methods

SHRs were randomly assigned to four treatment groups, including non-treated group, captopril, SNX, and captopril + SNX-treated groups. Their body weight and systolic blood pressure (SBP) were measured weekly. Histopathological examination was analyzed through Masson staining and hematoxylin and eosin staining. Biochemical analyses, ELISA, and western blot were used to analyze their combining mechanism.

Results

In this experiment, this combinatorial therapy significantly reduced aortic wall thickness, increased the content of NO, NOS and eNOS, decreased the content of bradykinin and endothelin 1(ET-1), and regulated the levels of TG, TC and HDLC back to normal, which suggested they could induce vasodilation and lower blood pressure. Meanwhile, histological examination alleviated that captopril + SNX remarkably inhibited renal injury, including tubular disorder, inflammatory cell infiltration and fibrosis. They down-regulated the serum levels of BUN and Cr, protein expression of IL-1β, NF-κB, Bax, Cyt c, caspase 3, 8 and 9 in kidney tissues and significantly increased the levels of Bcl-2 in kidney tissues compared with monotherapy group.

Conclusion

The combinatorial treatment of SNX and captopril lowered blood pressure through adjusting NO/NOS, ET-1 and dyslipidemia profile. Furthermore, this treatment alleviated the kidney damage via reducing the release of inflammatory factors and the expression of apoptotic markers. Therefore, these results provided a rationale for future clinical use of SNX combined with captopril in antihypertensive and protecting renal functions in hypertension.

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Abbreviations : Ang II, BUN, cGMP, Cr, Cyt c, eNOS, ET-1, HDLC, HE, IL, LDLC, NF-κB, SBP, SHR, TC, TG, TNF-α, TNOS, TUNEL, WKY

Keywords : Shunaoxin pill, Captopril, Combinatorial treatment, Antihypertension, Renoprotection


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