Datura stramonium Leaf Extract Exhibits Anti-inflammatory Activity in CCL4-Induced Hepatic Injury Model by Modulating Oxidative Stress Markers and iNOS/Nrf2 Expression

Abstract

Background. Inflammation is a frequent phenomenon in the pathogenesis of hepatic disorders leading to fibrosis and cirrhosis. Phytopharmaceuticals developed from traditional medicine can provide effective therapeutic alternatives to conventional medications. Datura stramonium (DS) has reported traditional uses in inflammatory diseases. In this study, we have tried to validate its potential as a source of anti-inflammatory agents. Methods. Powdered leaf part of DS was extracted using ethyl acetate (EA) to provide the extract (DSL-EA). Lymphocyte and macrophage viability and acute toxicity assays established the safety profile, while nitric oxide (NO) scavenging assay estimated the in vitro anti-inflammatory potential. Noninvasive anti-inflammatory, antidepressant, and antinociceptive activities were monitored using BALB/c mice using low and high doses (150 and 250 mg/kg). Major inflammatory studies were performed on Sprague-Dawley male rats using CCl4-induced liver injury model. Disease induction was initiated by intraperitoneal injections of CCl4 (1 mL/kg of 30% CCl4 in olive oil). The rats were divided into six groups. The anti-inflammatory potential of DSL-EA in low and high doses (150 and 300 mg/kg, respectively) was assessed through hematological, biochemical, liver antioxidant defense, oxidative stress markers, and histological studies as well as the expression of Nrf2 and iNOS. Results. DSL-EA exhibited prominent in vitro NO scavenging (IC50: 7.625 ± 0.51 μg/mL) and in vivo anti-inflammatory activity in paw and anal edema models. In CCl4 model, hematological investigations revealed vasotonic effects. Liver functionality was significantly ( P < 0.001 − 0.05 ) improved in DSL-EA-treated rats. The activity level of endogenous antioxidant enzymes in liver tissues was improved in a manner identical to silymarin. The extract reduced the percent concentration of oxidative stress markers in liver tissues. Furthermore, DSL-EA displayed restorative effects on histological parameters (H and E and Masson’s trichrome staining). Immunohistochemistry studies showed marked decline in Nrf2 expression, while overexpression of iNOS was also observed in disease control rats. The damage was distinctly reversed by the extract.

Datura stramonium Flowers as a Potential Natural Resource of Bioactive Molecules: Identification of Anti-Inflammatory Agents and Molecular Docking Analysis

“…However, leaf and seed extracts showed an SI of 1.47 and 0.62, respectively, indicating that both extracts showed a NO inhibitory effect at toxic concentrations. Previous studies have shown that D. stramonium ethyl acetate leaf extract exhibited a NO scavenging effect with an IC 50 value of 7.625 ± 0.551 µg/mL [ 38 ]. The toxicity effect of the extract has also been assessed, showing no significant cytotoxicity against isolated normal human lymphocytes and against macrophage isolated from rat peritoneum, even at the highest concentration (20 µg/mL) [ 38 ].…”

Anti-Diabetic Effects of the 80% Methanolic Extract of Datura Stramonium Linn (Solanaceae) Leaves in Streptozotocin- Induced Diabetic Mice

“…This finding revealed that the median lethal dose (LD 50 ) of the plant extract is greater than 2000 mg/kg, which is similar to previous study done on the same plant leaves. 21 …”

Activities of Datura stramonium Extracts against Clinical Pathogens

“…"Plants have always been a source of drugs for the treatment of human ailments, and millions of people in the world rely on medicinal plants for primary health care" [1][2][3]. In this study, the antibacterial activities of the extracts of D. stramonium pulp, seed and leaf using 50% and 75% ethanol as extraction solvents were conducted against some clinically isolated human pathogenic microorganisms.…”

“…Plant extracts contain extensive range of chemical compounds that can be used to treat long-lasting diseases as well as transmittable infections [1][2][3]. "These chemical compounds which include tannins, alkaloids, terpenoids and flavonoids exhibit antimicrobial, antioxidant, antiinfectious and antitumor activities" [1][2][3][4]. "During the past decades, infectious diseases have been the leading cause of death throughout the globe, particularly in the developing countries" [5].…”