Annona muricata Ethanolic Leaf Extract Attenuates Dexamethasone Induced Oxidative Stress, Dyslipidemia and Hepatotoxicity in Rats through Upregulation of Endogenous Antioxidant Enzymes and Lipid Profile Normalization

Abstract

Background: The therapeutic use of dexamethasone is often associated with adverse effects such as oxidative stress, dyslipidemia, and hepatotoxicity, primarily due to the generation of reactive oxygen species and disruption of metabolic homeostasis. Natural plant‑based antioxidants have gained attention for their potential to mitigate these complications. Aim: This study aimed to evaluate the protective effects of ethanolic leaf extract of Annona muricata against dexamethasone‑induced oxidative stress, lipid abnormalities, and liver dysfunction in Wistar rats. Methodology: Thirty adult male Wistar rats were randomly divided into five groups (n = 6). Group I served as the normal control (normal saline). Group II received dexamethasone (1 mg/kg, i.p.) to induce oxidative and metabolic disturbances. Groups III, IV and V were co‑treated with dexamethasone (1 mg/kg, i.p.) plus graded doses (100, 200, and 400 mg/kg, orally) of Annona muricata ethanolic leaf extract, respectively. Treatments were administered for 14 consecutive days. Biochemical analyses were conducted to assess oxidative stress markers (malondialdehyde, nitric oxide, reduced glutathione), antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase), lipid profile (total cholesterol, triglycerides, low‑density lipoprotein), and liver function enzymes (alanine aminotransferase, aspartate aminotransferase). Results: Dexamethasone administration significantly increased oxidative stress markers, lipid profile indices, and liver enzyme levels, while significantly reducing antioxidant enzyme activities (p < 0.05). Treatment with Annona muricata extract significantly and dose‑dependently reversed these effects by reducing malondialdehyde and nitric oxide levels, enhancing antioxidant enzyme activities, improving lipid profile parameters, and restoring liver enzyme levels toward normal. Conclusion: The ethanolic leaf extract of Annona muricata exhibits potent antioxidant, hypolipidemic, and hepatoprotective effects against dexamethasone‑induced toxicity, likely mediated through enhancement of endogenous antioxidant defense systems and normalization of lipid metabolism. These findings support its potential as a natural therapeutic agent for managing glucocorticoid‑induced metabolic and hepatic disorders.