Calluna vulgaris Crude Extract Reverses Liver Steatosis and Insulin Resistance-Associated-Brain Lesion Induced by CCl4 Administration

Abstract

Fatty liver (FL) is one of the most prevalent diseases in the world, characterized by insulin resistance and hyperlipidemia, which consequently lead to neurodegenerative disorders through the induction of oxidative stress-inflammatory axis, which alters the neurotransmitters’ levels. Calluna vulgaris (CV), also known as heather, has anti-inflammatory and antidepressant properties, making it a promising candidate for treating steatosis and brain lesions. This study aimed to assess the prophylactic and therapeutic effect of CV extract on brain dysfunction associated with steatosis. FL was induced in rats by CCl4 oral administration (50 µL/Kg in olive oil three times/week) for six weeks. The protection group received 200 mg/kg CV extract orally for two weeks before and two weeks during FL induction, while the treatment group was orally administered CV extract after FL induction for one month. The biochemical parameters revealed that CCl4 administration induced hepatotoxicity as blood-liver function parameters (AST, ALT, ALP, protein, and LDH) were increased by 1.8, 1.4, 2, 2.4, and 1.2-fold, respectively. Moreover, insulin resistance was characterized by a two-fold increase in the glucose, insulin, and lipid profile when compared to control one, at p < 0.05. Steatosis liver demonstrated a two-fold increase in all following parameters— acetaldehyde (AC), prooxidant (TBARS), acetylcholine esterase (AChE), monoamine oxidase (MAO), hyaluronidase, and ATPase—when compared to control one, at p < 0.05. CCl4 administration led to brain lesions where the brain level of TBARS, insulin, cholesterol, AChE, and MAO was progressively increased by 2, 1.6, 2.2, 4, and 1.6-fold, respectively, that was associated with reduced glucose (8-fold) and GSH (2-fold) than that of control level, at p < 0.05. CV extract as a prophylactic and therapeutic agent increased GSH and decreased TBARS of both the liver and brain than that of induced group, at p < 0.05, normalized the activities of AChE and MAO, and increased insulin sensitivity where they successfully decreased the HOMA-IR, glucose, TG, and cholesterol compared to than that of induced group, at p < 0.05. This positive effect of CV extract contributed to the presence of polyphenolic compounds such as catechins (5.501 ± 0.056 µg/g extract), gallic (3.525 ± 0.143 µg/g) extract, and protocatechuic acid (2.719 ± 0.132 µg/g extract). Therefore, we concluded that FL induced brain dysfunction through the formation of ROS and elevation of insulin and lipid inside the brain tissue, which alter the amount of neurotransmitter and cellular energy production. Rich in polyphenolic compounds, CV extract functions as an antioxidant, antidiabetic, hepatoprotective, inhibitor of neurotransmitter catabolizing enzymes, and a regulator for energy production. Therefore, it can be used as a preventative or treatment for NAFLD and brain damage.