Centella asiatica (L.) Urb. Prevents Hypertension and Protects the Heart in Chronic Nitric Oxide Deficiency Rat Model

Abstract

Background: Hypertension is a major risk factor for cardiovascular disease (CVD), which is the number one cause of global mortality. The potential use of natural products to alleviate high blood pressure has been demonstrated to exert a cardioprotective effect. Centella asiatica (L.) Urb. belongs to the plant family Apiaceae (Umbelliferae). It contains a high amount of triterpenoid and flavonoid that have antioxidant properties and are involved in the renin-angiotensin-aldosterone system which is an important hormonal system for blood pressure regulation. Objective: This study aimed to investigate the effects of C. asiatica ethanolic extract on blood pressure and heart in a hypertensive rat model, which was induced using oral N(G)-nitro-l-arginine methyl ester (l-NAME). Methods: Male Sprague-Dawley rats were divided into five groups and were given different treatments for 8 weeks. Group 1 only received deionized water. Groups 2, 4, and 5 were given l-NAME (40 mg/kg, orally). Groups 4 and 5 concurrently received C. asiatica extract (500 mg/kg, orally) and captopril (5 mg/kg, orally), respectively. Group 3 only received C. asiatica extract (500 mg/kg body weight, orally). Systolic blood pressure (SBP) was measured at weeks 0, 4, and 8, while serum nitric oxide (NO) was measured at weeks 0 and 8. At necropsy, cardiac and aortic malondialdehyde (MDA) contents, cardiac angiotensin-converting enzyme (ACE) activity, and serum level of brain natriuretic peptide (BNP) were measured. Results: After 8 weeks, the administrations of C. asiatica extract and captopril showed significant (p < 0.05) effects on preventing the elevation of SBP, reducing the serum nitric oxide level, as well as increasing the cardiac and aortic MDA content, cardiac ACE activity, and serum brain natriuretic peptide level. Conclusion: C. asiatica extract can prevent the development of hypertension and cardiac damage induced by l-NAME, and these effects were comparable to captopril.

Keywords: Centella asiatica; cardiac damage; hypertension; nitric oxide; nitro-l-arginine methyl ester.

FIGURE 1

Rat body weight before and after administration of l-NAME (40 mg/kg orally) and C. asiatica extract (500 mg/kg orally) or captopril (5 mg/kg orally) during the 8-weeks of study. The values represent mean ± SEM (n = 6). ^#versus baseline (p < 0.05), ^aversus control (p < 0.05), ^bversus C. asiatica (p < 0.05).

FIGURE 2

Systolic blood pressure in rats treated with concurrent l-NAME (40 mg/kg orally) and C. asiatica (500 mg/kg orally) or captopril (5 mg/kg orally). Line graph represent mean ± SEM (n = 6). ^aversus control (p < 0.05), ^bversus l-NAME (p < 0.05).

FIGURE 3

Percentage of plasma nitric oxide (NO) change in rats given C. asiatica extract (500 mg/kg orally) and captopril (5 mg/kg orally) together with l-NAME (40 mg/kg orally) for 8 weeks. Bars represent mean ± SEM (n = 6). ^aversus control (p < 0.05), ^bversus l-NAME (p < 0.05), ^cversus C. asiatica (p < 0.05).

FIGURE 4

Cardiac angiotensin-converting enzyme (ACE) activity in rats treated with C. asiatica extract (500 mg/kg orally) or captopril (5 mg/kg orally) together with l-NAME (40 mg/kg orally) for 8 weeks. Bars represent mean ± SEM (n = 6). ^aversus control (p < 0.05), ^bversus l-NAME (p < 0.05).

FIGURE 5

The effects of C. asiatica (500 mg/kg orally) and captopril (5 mg/kg orally) on (A) aortic and (B) cardiac TBARS content in l-NAME-administered rats (40 mg/kg orally) after 8 weeks. Bars represent mean ± SEM (n = 6). ^aversus control (p < 0.05), ^bversus l-NAME (p < 0.05).

FIGURE 6

Serum B-natriuretic peptide (BNP) level in rats co-treated with l-NAME (40 mg/kg orally) and C. asiatica extract (500 mg/kg orally) or captopril (5 mg/kg orally) for 8 weeks. Bars represent mean ± SEM (n = 6). ^aversus control (p < 0.05), ^bversus l-NAME (p < 0.05).

FIGURE 7

A schematic diagram on the role of NO deficiency in l-NAME-induced hypertension and cardiotoxicity in rats. Treatment with C. asiatica extract exhibited anti-hypertensive and cardioprotective effects via the enhancement of NO bioavailability, the suppression of RAAS and amelioration of oxidative stress status in l-NAME-treated group.