Evaluation of the Therapeutic Potential of the Methanolic Extract and Fractions of Datura stramonium in Paracetamol-intoxicated Rabbits

Introduction: Datura stramonium (DS) possesses strong medicinal and therapeutic potential but has been rarely evaluated in this context. Methods: The present study was intended to evaluate the antioxidant, hepatoprotective, and nephroprotective potential of the crude methanolic leaf extract and ethyl acetate, chloroform, n-hexane, and aqueous fractions of DS in paracetamol-intoxicated rabbits. Paracetamol (2 g/Kg BW) was applied to induce liver and kidney injury in rabbits while the methanolic extract and fractions of DS were applied in the dose range of 150 mg/Kg to 300 mg/Kg body weight for 21 days. Histopathology of the liver, and kidney and analysis of ALT (Alanine Transaminase), ALP (Alkaline Phosphatase), total bilirubin, serum urea, serum creatinine, and serum uric acid were carried out. In vitro antioxidant potential of the extract and fractions of DS was carried out through DPPH (1,1-diphenyl 2-picrylhydrazyl) free radical scavenging assays. Results: The hepatoprotective and nephroprotective potential of the extract and fractions of DS at the dose level of 300 mg/Kg BW was highly significant (P ˂ 0.01). ALT was found elevated in the paracetamol-treated group (117.3 ± 1.61 U/L) compared to the group treated with methanolic extract of DS, (57.3 ± 0.87 U/L) and normal control group (60.6 ± 1.58 U/L) at 300 mg/kg BW. Elevated levels of ALP (120 ± 1.58 U/L) and Bilirubin (1.6 ± 0.32 mg/dl) were found in the paracetamol-treated group compared with the group treated with methanolic extract of DS (67.5 ± 1.35 U/L; 0.2 ± 1.0 mg/dl) and normal control group (70.1 ± 1.53 U/L; 0.4 ± 0.16 mg/dl) respectively at 300 mg/kg BW. The methanolic extract of DS produced a marked scavenging activity of the DPPH free radicals (88.2 ± 0.006%) followed by the fractions of DS compared to ascorbic acid (95.5 + 0.003%) at a concentration of 1000 µg/ml. The effects were comparable to those produced by ascorbic acid. Liver and kidney histology of the rabbits treated with extract, fractions, and ascorbic acid of DS caused reductions in the pathological features compared to the paracetamol-treated animals. The histological observations and chemical pathological alterations demonstrated the significant hepatoprotective and nephroprotective benefits of the DS extract and its fractions. Conclusion: It has been concluded that the methanolic extract and fractions of DS possess antioxidant, hepatoprotective, and nephroprotective properties in paracetamol-intoxicated rabbits.