Peperomia pellucida (L.) Kunth as an angiotensin-converting enzyme inhibitor in two-kidney, one-clip Goldblatt hypertensive rats

Abstract

Backgroud: Peperomia pellucida (L.) Kunth has been used widely to treat headache, kidney disease, fever, and hypertension. Previous in vitro studies discovered that the flavonoid-rich extract of this plant has potential hypotensive effects, specifically angiotensin-converting enzyme (ACE)-inhibitory activity. However, there is insufficient scientific evidence to validate the result in vivo.

Purpose: This study investigated the dose dependencies of the effects of the ethyl acetate fraction of the ethanolic extract of this plant on blood pressure and biomarkers associated with the renin-angiotensin-aldosterone systems (RAAS), such as angiotensin II (AII) and the plasma renin concentration (PRC).

Study design: In total, 30 two-kidney, one-clip (2K1C) hypertensive model rats were divided into five groups (n = 6 each): model group, captopril 25 mg/kg BW group, and three different ethyl acetate groups (25, 50, and 100 mg/kg BW). Another six rats comprised the sham group.

Methods: Renal hypertensive rats (RHRs) were generated using stainless steel modification clips. Drugs were administered via oral gavage for 2 consecutive weeks. Blood pressure was measured weekly prior to treatment. Blood samples were collected before treatment and after the last dose to measure AII and PRC. The left kidney was isolated for histopathological examination.

Results: Blood pressure, AII levels, and PRC were elevated after 6 weeks in RHRs. Treatment with captopril and the ethyl acetate fraction of P. pellucida (L.) Kunth decreased blood pressure, AII levels, and PRC. The ethyl acetate fraction at a dose of 50 mg/kg BW had similar ACE-inhibitory effects as captopril. Histopathological examination disclosed coagulative necrosis in clipped kidneys. Impairment was alleviated in a dose-dependent manner by P. pellucida (L.) Kunth, similarly as observed in the captopril group.

Conclusion: P. pellucida (L.) Kunth targets the renin-angiotensin-aldosterone system, which might explain its antihypertensive effects.

Keywords: 2K1C Goldblatt; 2K1C, two-kidney one-clip; ACE inhibitor; ACE, angiotensin-converting enzyme; AII, angiotensin II; Antihypertension; DBP, diastolic blood pressure; PPF, Peperomia pellucida fraction; PRC, plasma renin concentration; Peperomia pellucida (L.) Kunth; RAAS, the renin–angiotensin–aldosterone system; RHR, renal hypertensive rat; SBP, systolic blood pressure.

Fig. 1

Modification clip.

Fig. 2

Changes of systolic (A) and diastolic (B) blood pressure in the sham, model, captopril, and PPF groups. Note: Sham: no treatment; Model: untreated RHR model group; Captopril: RHR model treated with captopril (25 mg/kg BW, p.o.); PPF low: RHR model treated with 25 mg/kg BW PPF (p.o.); PPF medium: RHR model treated with 50 mg/kg BW PPF (p.o.); PPF high: RHR model treated with 100 mg/kg BW PPF (p.o.).

Fig. 3

Histological observation of the left kidney in 2K1C rats. a. Sham; b. Model; c. Captopril; d. PPF low; e. PPF medium; f. PPF high. → coagulative necrosis; Sham: no treatment; Model: untreated RHR model group; Captopril: RHR model treated with captopril (25 mg/kg BW, p.o.); PPF low: RHR model treated with 25 mg/kg BW PPF (p.o.); PPF medium: RHR model treated with 50 mg/kg BW PPF (p.o.); PPF high: RHR model treated with 100 mg/kg BW PPF (p.o.).