Protective effects of Morinda Citrifolia ethanolic leaf extract on the aorta and liver of postmenopausal Sprague- Dawley rats fed with thermoxidized palm oil diet

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide and it is manifested by atherosclerosis. Alteration of lipid metabolism towards a more atherogenic form that occurs after menopause promotes fat deposition in the liver (hepatic steatosis) and aorta. Oxidative stress in the liver due to hepatic fat accumulation aggravates the development of both non-alcoholic fatty liver disease (NAFLD) and atherosclerosis in postmenopausal subjects. The aim of this study was to investigate the effects of Morinda citrifolia (MC) ethanolic leaf extract on the aorta and liver of postmenopausal rats fed with thermoxidized palm oil (TPO) diet. Thirty eight female Sprague-Dawley rats were divided into five groups; Sham (n=7), Ovariectomized (OVX, n=7), Ovariectomized with simvastatin 10 mg/kg (OVX+ST, n=8), Ovariectomized with low dose MC 500 mg/kg (OVX+MCLD, n=8), and Ovariectomized with high dose MC 1000 mg/kg (OVX+MCHD, n=8). Bilateral ovariectomy was performed to induce oestrogen deficiency state. Three weeks after the recovery period, all the ovariectomized groups were fed with TPO diet with respective treatments whereas the Sham group was fed with normal diet. Physiological monitoring such as dietary intake, body weight and blood pressure was done throughout the study. After three months of treatment all the rats were sacrificed. Blood, aortic and liver tissues were collected for biochemical and histopathological analyses. Results revealed significant increased (P<0.05) in the food intake and body weight in all the ovariectomized groups compared to the Sham. Diastolic blood pressure (DBP) and mean arterial pressure (MAP) were significantly elevated in the untreated OVX group compared to the Sham group. Treatment with MCHD significantly lowered the systolic blood pressure (SBP) and MAP compared to the OVX group. MCHD also significantly lowered the total cholesterol (TC) level compared to the OVX group. High-density lipoprotein (HDL) level was significantly decreased in the untreated OVX group compared to the Sham. TC/HDL was significantly higher in the OVX and OVX+MCLD groups. However, there were no significant difference in the serum low density lipoprotein (LDL), triglycerides (TG), C-reactive protein (CRP), 11Beta hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1) and liver enzymes. Oxidative stress marker malondialdehyde (MDA) was significantly increased in the untreated OVX group and OVX+MCLD compared to the normal Sham. Treatment with MCHD significantly increased the antioxidant enzymes (SOD and GPx) in the liver. Histopathological and ultrastructural evaluation revealed that MCHD maintained the normal histological features of the aorta and liver comparable to that of the normal Sham and protected against the development of hepatic steatosis and late atherosclerotic lesions. In conclusion, we provided evidence that MC leaf extract possess protective effects against aortic pathology, liver oxidative stress and hepatic steatosis.