Soursop leaf extract and fractions protects against L-NAME-induced hypertension and hyperlipidemia

Abstract

Introduction: Despite the high phenolic content of Annona muricata, little is known about its anti-hypertensive and antihyperlipidemic properties. This study evaluated the anti-hypertensive and antihyperlipidemic potential of A. muricata leaf extracts.

Materials and methods: Forty-two male Wistar rats were divided into seven groups of six animals each. N-nitro-L-arginine methyl ester (L-NAME) was used to induce hypertension and hyperlipidemia.

Results: Phytochemical screening of Annona muricata leaf extracts (AMLE) revealed the presence of saponins, alkaloids, flavonoids, tannins, coumarins, steroids, terpenoids, and phenols. Comparing the methanol extract with the ethyl acetate fraction, quantification revealed that the methanol extract contained more phenolics, flavonoids, and alkaloids. The AMLE rats significantly reduced triglycerides, total cholesterol, LDL, VLDL, atherogenic index, coronary risk index, and blood pressure. The significant decrease in GSH, catalase, SOD, GST, and oxidative stress markers (MDA, nitrites, and MPO) was reversed by AMLE in a dose-dependent manner. Also, the elevated serum levels of TNF-α and IL-1β in the hypertensive rats were attenuated in the treatment groups.

Discussion: This study suggests the potential ameliorative effects of Annona muricata leaf extracts against L-NAME-induced hypertension in rats. Notably, the study showed the antioxidant and anti-inflammatory properties of A. muricata leaf extracts, which is seen in its ability to attenuate oxidative stress and inflammatory cytokines in L-NAME-induced hypertensive rats. A. muricata extracts also decreased atherogenic risk and improved lipid profiles.

Keywords: Annona muricata (Annonaceae); N-nitro-L-arginine-methyl ester; antioxidants; blood pressure; captopril.

Figure 1

Effect of A. muricata extracts on body weight in L-NAME-induced hypertensive rats. Results are expressed as mean ± S.E.M (n = 5). ^#p < 0.05 compared with control group, ^*p < 0.05 compared with L-NAME group.

Figure 2

Effect of A. muricata extracts on reduced glutathione (GSH) in the aorta, heart and kidney of L-NAME-induced hypertensive rats. Results are expressed as mean ± S.E.M (n = 5). ^#p < 0.05 compared with control group, ^*p < 0.05 compared with L-NAME group.

Figure 3

Effect of Annona muricata extracts on Malondialdehyde (MDA) in the aorta, heart and kidney of L-NAME-induced hypertensive rats. Results are expressed as mean ± S.E.M (n = 5). ^#p < 0.05 compared with control group, ^*p < 0.05 compared with L-NAME group.

Figure 4

Effect of Annona muricata extracts on nitrite concentration in the aorta, heart, and kidney of L-NAME-induced hypertensive rats. Results are expressed as mean ± S.E.M (n = 5). ^#p < 0.05 compared with control group, ^*p < 0.05 compared with L-NAME group.

Figure 5

(A) Effect of Annona muricata extracts on catalase concentration in the aorta, heart and kidney of L-NAME-induced hypertensive rats. Results are expressed as mean ± S.E.M (n = 5). ^#p < 0.05 compared with control group, ^*p < 0.05 compared with L-NAME group.

Figure 6

Effect of Annona muricata extracts on SOD concentration in the aorta, heart and kidney of L-NAME-induced hypertensive rats. Results are expressed as mean ± S.E.M (n = 5). ^#p < 0.05 compared with control group, ^*p < 0.05 compared with L-NAME group.

Figure 7

Effect of Annona muricata extracts on GST concentration in the aorta, heart and kidney of L-NAME-induced hypertensive rats. Results are expressed as mean ± S.E.M (n = 5). ^#p < 0.05 compared with control group, ^*p < 0.05 compared with L-NAME group.

Figure 8

Effect of Annona muricata extracts on MPO concentration in the aorta, heart and kidney of L-NAME-induced hypertensive rats. Results are expressed as mean ± S.E.M (n = 5). ^#p < 0.05 compared with control group, ^*p < 0.05 compared with L-NAME group.

Figure 9

Effect of Annona muricata extracts on tumor necrosis factor-alpha and interleukin-1 beta in L-NAME-induced hypertensive rats. Results are expressed as mean ± S.E.M (n = 5). ^#p < 0.05 compared with control group, ^*p < 0.05 compared with L-NAME group.

Figure 10

Photomicrograph of aorta sections. (A) Photomicrograph showing normal appearance. The aortic media appear normal, and there are many normal parallel lamellae (white arrow). Tunica intima appears normal (slender arrow). (B) Photomicrograph showing aortic media appearing normal. There are many normal parallel lamellae (white arrow). Tunica intima appears normal (slender arrow). The serosa layer shows moderate infiltration of inflammatory cells (black arrow). (C) Photomicrograph showing normal appearance, the aortic media appear normal. There are many normal parallel lamellae (white arrow). Tunica intima appears normal (slender arrow). (D) Photomicrograph showing normal appearance, the aortic media appear normal, and there are many normal parallel lamellae (white arrow). Tunica intima appears normal (slender arrow). A mildly infiltrated serosa layer is seen (black arrow). (E) Photomicrograph showing the normal appearance, the aortic media appear normal. There are many normal parallel lamellae (white arrow). Tunica intima seen show mild focal constriction (slender arrow).

Figure 11

Photomicrograph of Heart sections. (A) Photomicrograph showing normal epicardial layer (white arrow) and normal myocardial layer. The myocytes are normal. (B) Photomicrograph showing the normal epicardial layer. Tunica intima seen also appear normal. The serosa layer shows mild infiltration of inflammatory cells (black arrow). (C) Photomicrograph showing normal epicardial layer and normal myocardial layer (blue arrow). The myocytes are also normal. (D) Photomicrograph showing area of moderate fibrosis (white arrow). (E) Photomicrograph showing normal epicardial and myocardial layers seen (blue arrow). The myocytes are also normal.

Figure 12

Photomicrograph of kidney sections. (A) Photomicrograph showing the renal cortex reveals normal glomeruli with normal mesangial cells and capsular spaces (white arrow), the renal tubules appear normal (blue arrow), and the interstitial spaces appear normal (slender arrow). (B) Photomicrographs showing the renal cortex. It shows normal glomeruli with normal mesangial cells and capsular spaces, the renal tubules appear normal (blue arrow), and the interstitial spaces appear mildly infiltrated by inflammatory cells. Few tubules are seen degenerated (black arrow). (C) Photomicrographs showing normal architecture. The renal cortex shows normal glomeruli with normal mesangial cells and capsular spaces (white arrow), the renal tubules appear normal (blue arrow), and the interstitial spaces show area of mild infiltration of inflammatory cells (slender arrow). (D) Photomicrographs showing the renal cortex which shows normal glomeruli with normal mesangial cells and capsular spaces (white arrow). The renal tubules appear normal (blue arrow), and the interstitial spaces show moderate vascular congestion (slender arrow). (E) Photomicrographs showing normal architecture as seen in higher magnification x400, the renal cortex showing normal glomeruli with normal mesangial cells and capsular spaces (white arrow). The renal tubules appear normal (blue arrow) and the interstitial spaces show scanty infiltration of inflammatory cells (slender arrow).