Extract of Plantago asiatica L. Seeds Ameliorates Hypertension in Spontaneously Hypertensive Rats by Inhibition of Angiotensin Converting Enzyme.

Ren-Chao Tong,Zheng-Tao Wang,Qi-Ming Yang,Li Yang,Meng Qi,Dan-Dan Wang,Ji-Ping Lan,Peng-Fei Li

doi:10.3389/fphar.2019.00403

Abstract

Plantago asiatica L. seeds is a common folk medicine with a long history of medical use in China because of its antipyretic, diuretic, and expectorant properties. It has been applied to treat hypertension clinically due to its diuresis, however, its efficacy and mechanisms on anti-hypertension has not been reported yet to our knowledge. In this study, we investigated the antihypertensive effect and underlying mechanisms of P. asiatica L. seeds extract (PASE) in spontaneously hypertensive rat (SHR). Male SHRs were treated with 2.5 mg/kg of fosinopril (FOS) and 400 mg/kg of PASE orally per day for once or 12 weeks. SHR or Wistar-Kyoto rats (WKY) receiving vehicle (distilled water) was used as control. The results demonstrated systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP) were significantly lowered after single and long-term intragastric administration of PASE. The cardiac and aortic index and collagen accumulation were improved in the PASE group compared with the SHRs group. Meanwhile, PASE treatment remarkably reduced urine total protein, the ratio of serum urea nitrogen to serum creatinine, and increased serum potassium. The levels of serum angiotensin I (Ang I), angiotensin II (Ang II), the ratio of Ang II to Ang I, and aldosterone (ALD) were lowered after treatment of PASE. Besides, PASE and its major active constituents of phenylethanoid glycosides, including isoacteoside, plantamajoside and acteoside, were found to effectively inhibit angiotensin-converting enzyme (ACE) activation in vitro. These findings suggest that PASE has the antihypertensive effect that may involve a mechanism of ACE inhibition and simultaneously protect organ damage against hypertension.

Highlights

Hypertension is one of the major threats for global human health, which could induce a series of damages to brain vessel, heart, and kidney (WHO, 2013)
Previous studies have shown that P. asiatica L. seed contains polysaccharides, phenylethanoid glycosides, iridoids, flavonoids, triterpenes, et al (Huang et al, 2014; Qi et al, 2015; Wang et al, 2016), which account for a variety of properties such as immunomodulatory, anti-oxidation, anti-inflammation, liver protection, facilitating defecation, improving lipids/glucoside metabolism, and so on (Xu et al, 2004; Hannan et al, 2006; Huang et al, 2009; Geng et al, 2010; Yin et al, 2010; Lim et al, 2013; Yang et al, 2017)
The chemical composition of P. asiatica L. seeds (PASE) was determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) in positive ionization scan mode and negative ionization scan mode (Supplementary Figure S1)

Summary

Introduction

Hypertension is one of the major threats for global human health, which could induce a series of damages to brain vessel, heart, and kidney (WHO, 2013). Traditional herbal medicines have attracted special attention on hypertension treatment and new drug development since they contain various natural products with reported antihypertensive activities, such as flavonoids, terpenes, alkaloids, and phenolic compounds (Maione et al, 2013; Bai et al, 2015). The effective components and mechanism of P. asiatica L. seed on modern hypertension treatment are still unclear. We demonstrated that P. asiatica L. seeds can reduce blood pressure and protect heart, aorta, and kidney in rat models, indicating the potential use of P. asiatica L. seed in hypertension treatment

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Conclusion