Lagerstroemia indica methanolic extract alleviates CCl4-induced liver toxicity via modulation of Nrf2 signaling pathway in rats

Objective: To assess the hepatoprotective effects of methanolic extract of Lagerstroemia indica leaves on carbon tetrachloride (CCl 4 )-induced liver damage in rats. Methods: Fifty male Sprague Dawley rats were divided into five groups: the normal control, the CCl 4 group, the CCl 4 group treated with silymarin (200 mg/kg) or Lagerstroemia indica extract (200 and 400 mg/kg). Oxidative stress, inflammatory, and apoptotic markers, as well as liver enzymes were analyzed. Histopathological studies were performed to examine the effect of the plant extract on liver structure. In addition, quantitative RT-PCR analysis was carried out to determine Nrf2, Keapl, HMOX1, and NQO1 expression. Results: Lagerstroemia indica extract significantly improved liver function by reducing aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin levels. It also enhanced the activities of catalase, superoxide dismutase, and glutathione peroxidase, increased glutathione content, and reduced the levels of malondialdehyde, nuclear factor kappa-B, tumor necrosis factor-α, interleukin-1β, interleukin-6, cyclooxygenase-2, Bax, caspase-3 and caspase-9. In addition, the mRNA expression levels of Nrf2, Keapl, HMOX1, and NQO1 were markedly downregulated by treatment with Lagerstroemia indica extracts. Histopathological examination revealed the extract confered protection against CCl 4 -induced liver damage as evidenced by reduced sinusoidal dilatation, thinner fibrotic septa, decreased vacuolar degeneration, and improved hepatic cord organization. Conclusions: Lagerstroemia indica extract possesses hepatoprotective activity by modulating the Nrf2-Keap1-HMOX1-NQO1 signaling pathway in a rat model of CCl 4 -induced liver damage.