Nonalcoholic steatohepatitis (
NAFLD) is a progressive form of
liver disease that leads to advanced
fibrosis. The present study was designed to assess the hepatoprotective effect of
thymoquinone (TQ) on liver functions,
insulin resistance, and
PPAR-γ expression in
NAFLD. Rats were divided into two main groups: one fed with normal rat chow diet and the other with high-fat high-
cholesterol diet group for 6 weeks. Every group was subdivided into three subgroups (n = 8): treated with saline, low dose TQ (10 mg/kg), high dose TQ (20 mg/kg). High fat high
cholesterol diet caused marked liver damage as noted in histopathology and significant increase in liver index, liver
enzymes. There was significant increase in the
insulin resistance, serum
cholesterol,
triglyceride,
PPAR-γ gene overexpression with significant decrease in HDL. Additionally, oxidative stress increased by measuring MDA associated with significant decrease in serum total
antioxidant capacity. As markers of
inflammation, hepatic TNF-α was significantly increased with decrease in
IL10. Further, there was increase in
BAX protein with decrease in Bcl as compared to control group. This model of 6 weeks high-fat high-
cholesterol diet showed minimal
fibrosis as noticed by increase MMP2 and Masson trichrome satin. Co-treatment with TQ improved all previous parameters. High dose was more effective, although mostly non-statistically significant. TQ may have a promising agent to improve hepatic steatosis, oxidative stress; inflammatory, apoptotic status,
fibrosis and so prevent liver damage in patients with
NAFLD. Although
PPAR-γ was significantly under-expressed by TQ,
insulin resistance was improved significantly suggesting a role of liver damage.