Anti-atherosclerotic and hepatoprotective effects of trihoney in hypercholestrolemic rabbits

Abstract

Cardiovascular diseases are major contributor to morbidity and mortality worldwide. Atherosclerosis is a leading cause to cardiovascular diseases in addition to its pathogenic association with non-alcoholic fatty liver disease (NAFLD). Protection against atherosclerosis and NAFLD constitutes a global aim. Modern trend has emerged to reintroduce natural products such as honey for management of these metabolic epidemics because of the less side effects perhaps. In the present study, Trihoney was investigated for its anti-atherosclerotic and hepatoprotective effects in diet induced hypercholesterolemic rabbits model. Forty-eight male New Zealand white rabbits were randomly assigned to one of 6 groups. First group was fed only commercial rabbit diet, second group was fed commercial rabbit diet with 0.6g of Trihoney/kg/day, third group was fed 1% cholesterol diet, fourth and fifth groups were fed 1% cholesterol diet with 0.3 and 0.6 g of Trihoney/kg/day while the last group was fed 1% cholesterol diet plus 2mg of atorvastatin/kg/day. Experiment continues for 12 weeks duration. Blood samples were withdrawn before and after the experimental period. Aorta and liver were harvested and processed for homogenate and histopathological studies. In the first phase, Trihoney was investigated for its lipid lowering and anti-inflammatory effects through analysis of serum lipids [total cholesterol (TC), low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c), triglycerides (TG) and TC/HDL risk ratio] and by assay of serum pro-atherogenic inflammatory cytokines [interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)]. The results showed that Trihoney had significant lipid lowering and marked anti-inflammatory effects. In the second phase, Trihoney was assessed for antioxidant function by analysing serum and aorta homogenate for superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA), in addition to analysing serum for oxidised-LDL (Ox-LDL). Results showed that Trihoney exerted significant antioxidant effects systemically as well as locally in the aorta. In the third phase, Trihoney was investigated of its effects on the atherosclerotic plaques, inflammatory adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and on homocysteine. Results showed that Trihoney had significant anti-inflammatory and vascular protective functions. In the fourth phase, Trihoney was examined for hepatoprotective function against NAFLD through histopathological study and via assay of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (T. Bil.), alkaline phosphatase (ALP), fasting glucose, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). In addition to antioxidant assay of liver homogenate for SOD, GPx and MDA. Results showed that under status of sustained hypercholesterolemia, Trihoney was able to normalise hepatic function in NAFLD induced hypercholesterolemia, Trihoney showed no effect on fasting glucose, insulin and HOMA-IR, Trihoney exhibited significant antioxidant effect against hepatic oxidative stress and it was protective against progression of NAFLD to non-alcoholic steatohepatitis (NASH). Accordingly, Trihoney has a potential protective role against atherosclerosis and NAFLD through hypocholesterolemic, antioxidant and anti-inflammatory functions. Further studies may be needed to explore possible molecular mechanisms underlying those health beneficial properties of Trihoney.