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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. <jats:italic>Datura stramonium<\/jats:italic> (DS) has reported traditional uses in inflammatory diseases. In this study, we have tried to validate its potential as a source of anti\u2010inflammatory agents. <jats:italic>Methods<\/jats:italic>. Powdered leaf part of DS was extracted using ethyl acetate (EA) to provide the extract (DSL\u2010EA). Lymphocyte and macrophage viability and acute toxicity assays established the safety profile, while nitric oxide (NO) scavenging assay estimated the <jats:italic>in vitro<\/jats:italic> anti\u2010inflammatory potential. Noninvasive anti\u2010inflammatory, antidepressant, and antinociceptive activities were monitored using BALB\/c mice using low and high doses (150 and 250\u2009mg\/kg). Major inflammatory studies were performed on Sprague\u2010Dawley male rats using CCl<jats:sub>4<\/jats:sub>\u2010induced liver injury model. Disease induction was initiated by intraperitoneal injections of CCl<jats:sub>4<\/jats:sub> (1\u2009mL\/kg of 30% CCl<jats:sub>4<\/jats:sub> in olive oil). The rats were divided into six groups. The anti\u2010inflammatory potential of DSL\u2010EA in low and high doses (150 and 300\u2009mg\/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. <jats:italic>Results<\/jats:italic>. DSL\u2010EA exhibited prominent <jats:italic>in vitro<\/jats:italic> NO scavenging (IC<jats:sub>50<\/jats:sub>: 7.625 \u00b1 0.51\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL) and <jats:italic>in vivo<\/jats:italic> anti\u2010inflammatory activity in paw and anal edema models. In CCl<jats:sub>4<\/jats:sub> model, hematological investigations revealed vasotonic effects. Liver functionality was significantly (<jats:italic>P<\/jats:italic> &lt; 0.001 \u2212 0.05) improved in DSL\u2010EA\u2010treated 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\u2010EA displayed restorative effects on histological parameters (H and E and Masson\u2019s 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.<\/jats:p>","DOI":"10.1155\/2022\/1382878","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T23:36:10Z","timestamp":1647473770000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["<i>Datura stramonium<\/i> Leaf Extract Exhibits Anti\u2010inflammatory Activity in CCL<sub>4<\/sub>\u2010Induced Hepatic Injury Model by Modulating Oxidative Stress Markers and iNOS\/Nrf2 Expression"],"prefix":"10.1155","volume":"2022","author":[{"given":"Bakht","family":"Nasir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf Ullah","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Waleed","family":"Baig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3128-2824","authenticated-orcid":false,"given":"Yusuf S.","family":"Althobaiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Faheem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6413-5957","authenticated-orcid":false,"given":"Ihsan-Ul","family":"Haq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1245049"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-016-1260-4"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026012"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006446"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2210-5-2"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)00809-2"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-5408.2002.00005.x"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8546-8-7"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i25.8082"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.5152\/tjg.2018.17330"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840120210"},{"key":"e_1_2_13_12_2","first-page":"115","article-title":"Medicinal plants against liver diseases","volume":"2","author":"Govind P.","year":"2011","journal-title":"IJPR"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105264"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-017-1744-x"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/1541-4337.12335"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-020-02975-8"},{"key":"e_1_2_13_17_2","article-title":"The genus Datura: from research subject to powerful hallucinogen","volume":"1998","author":"Bonde K.","year":"2001","journal-title":"Ethnobotanical Leaflets"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2006.01.002"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.3736\/jintegrmed2013016"},{"key":"e_1_2_13_20_2","first-page":"151","article-title":"Comparative studies on anti-inflammatory activity of Coriandrum sativum, Datura stramonium and Azadirachta indica","volume":"1","author":"Sonika G.","year":"2010","journal-title":"Asian Journal of Experimental Biological Sciences"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(02)00317-2"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10669-007-9024-9"},{"key":"e_1_2_13_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-08-102081-4.00015-0"},{"key":"e_1_2_13_24_2","unstructured":"GaireB. 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