{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:50:15Z","timestamp":1788850215824,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski\u2019s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm\/s); no blood\u2013brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-\u03baB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was &gt;20 \u00b5g\/mL as compared to cancer cells (Huh7.5; 17.32 \u00b1 1.43 \u00b5g\/mL). Daturaolone significantly inhibited NF-\u03baB and nitric oxide production with IC50 values of 1.2 \u00b1 0.8 and 4.51 \u00b1 0.92 \u00b5g\/mL, respectively. It significantly reduced inflammatory paw edema (81.73 \u00b1 3.16%), heat-induced pain (89.47 \u00b1 9.01% antinociception) and stress-induced depression (68 \u00b1 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.<\/jats:p>","DOI":"10.3390\/ph14121248","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:56Z","timestamp":1638314576000},"page":"1248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies"],"prefix":"10.3390","volume":"14","author":[{"given":"Muhammad Waleed","family":"Baig","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5509-8477","authenticated-orcid":false,"given":"Humaira","family":"Fatima","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3413-9150","authenticated-orcid":false,"given":"Nosheen","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-8127","authenticated-orcid":false,"given":"Hidayat","family":"Hussain","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Plant Biochemistry, Department of Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad K.","family":"Okla","sequence":"additional","affiliation":[{"name":"Botany and Microbiology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Al-Hashimi","sequence":"additional","affiliation":[{"name":"Botany and Microbiology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahidah H.","family":"Al-Qahtani","sequence":"additional","affiliation":[{"name":"Department of Food Sciences & Nutrition, College of Food & Agriculture Sciences, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamada","family":"AbdElgawad","sequence":"additional","affiliation":[{"name":"Integrated Molecular Plant Physiology Research (IMPRES), Department of Biology, University of Antwerp, 2020 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan-ul","family":"Haq","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_2","first-page":"641","article-title":"TNF-alpha signalling and inflammation: Interactions between old acquaintances","volume":"62","author":"Zelova","year":"2013","journal-title":"Inflamm. 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