Downregulation of hepatic fat accumulation, inflammation and fibrosis by nerolidol in purpose built western-diet-induced multiple-hit pathogenesis of NASH animal model

Western diet style (fast food), which includes fatty frozen junk food, lard, processed meats, whole-fat dairy foods, cream, mayonnaise, butter, snacks, and fructose, is a primary etiological determinant for developing nonalcoholic steatohepatitis (NASH) worldwide. Here the primary focus is to see the impact of naturally identified essential oil on disease mechanisms developed in an animal model using the same ingredients. Currently, symptomatic therapies are recommended for the management of NASH due to non-availability of specific treatments. Therefore, the present study was designed to evaluate the potential anti-NASH effect of nerolidol in a rat model fed with a purpose-built diet. The diet substantially induced insulin resistance, hepatic steatosis, dyslipidemia, and elevation of liver enzymes in the experimental animals. The levels of liver oxidative stress markers, nitrites (NO2–), serum pro-inflammatory cytokine (TNF-α) and hepatic collagen were increased in disease control rats. Nerolidol oral treatment in ascending dose order of 250 and 500 mg/kg substantially reduced the steatosis (macrovesicular and microvesicular), degeneration of hepatocytes, and inflammatory cells infiltration. The amounts of circulatory TNF-α and tissue collagen were also reduced at 500 mg/kg dose of nerolidol, expressing its anti-fibrotic effect. The current study described the multiple-hit pathophysiology of NASH as enhanced steatosis, pro-inflammatory markers, and oxidative stress in rats, which resulted in the development of vicious insulin resistance. Nerolidol treatment significantly reduced hepatic lipid accumulation and halted disease progression induced by a hypercaloric diet. [Display omitted] •Western-diet induced multiple-hit pathogenesis of NASH in the animal model.•Steatosis, inflammation, and oxidative stress crucially contribute to hepatic insulin resistance.•TNF-α and insulin levels are measured through ELISA technique.•Nerolidol prevented the accumulation of fat, AOPP, and collagen in hepatic tissues.