Anti-Inflammatory Potential of Daturaolone from <i>Datura innoxia</i> Mill.: In Silico, In Vitro and In Vivo Studies
Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from <i>Datura innoxia</i> Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Datur...
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MDPI AG
2021-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/12/1248 |
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| author | Muhammad Waleed Baig Humaira Fatima Nosheen Akhtar Hidayat Hussain Mohammad K. Okla Abdulrahman Al-Hashimi Wahidah H. Al-Qahtani Hamada AbdElgawad Ihsan-ul Haq |
| author_facet | Muhammad Waleed Baig Humaira Fatima Nosheen Akhtar Hidayat Hussain Mohammad K. Okla Abdulrahman Al-Hashimi Wahidah H. Al-Qahtani Hamada AbdElgawad Ihsan-ul Haq |
| author_sort | Muhammad Waleed Baig |
| collection | DOAJ |
| description | Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from <i>Datura innoxia</i> Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s 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–brain 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-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC<sub>50</sub>) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC<sub>50</sub> values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 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. |
| first_indexed | 2024-03-10T03:21:38Z |
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| id | doaj.art-980284356dd44a8eb99a68dd1d1e9efc |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T03:21:38Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj.art-980284356dd44a8eb99a68dd1d1e9efc2023-11-23T10:03:01ZengMDPI AGPharmaceuticals1424-82472021-11-011412124810.3390/ph14121248Anti-Inflammatory Potential of Daturaolone from <i>Datura innoxia</i> Mill.: In Silico, In Vitro and In Vivo StudiesMuhammad Waleed Baig0Humaira Fatima1Nosheen Akhtar2Hidayat Hussain3Mohammad K. Okla4Abdulrahman Al-Hashimi5Wahidah H. Al-Qahtani6Hamada AbdElgawad7Ihsan-ul Haq8Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, PakistanDepartment of Pharmacy, Quaid-i-Azam University, Islamabad 45320, PakistanDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, PakistanLeibniz Institute of Plant Biochemistry, Department of Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), GermanyBotany and Microbiology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaBotany and Microbiology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Food Sciences & Nutrition, College of Food & Agriculture Sciences, King Saud University, Riyadh 11451, Saudi ArabiaIntegrated Molecular Plant Physiology Research (IMPRES), Department of Biology, University of Antwerp, 2020 Antwerp, BelgiumDepartment of Pharmacy, Quaid-i-Azam University, Islamabad 45320, PakistanExploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from <i>Datura innoxia</i> Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s 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–brain 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-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC<sub>50</sub>) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC<sub>50</sub> values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 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.https://www.mdpi.com/1424-8247/14/12/1248<i>Datura innoxia</i>daturaoloneterpenoidanti-inflammatoryNF-<i>κ</i>Bnitric oxide |
| spellingShingle | Muhammad Waleed Baig Humaira Fatima Nosheen Akhtar Hidayat Hussain Mohammad K. Okla Abdulrahman Al-Hashimi Wahidah H. Al-Qahtani Hamada AbdElgawad Ihsan-ul Haq Anti-Inflammatory Potential of Daturaolone from <i>Datura innoxia</i> Mill.: In Silico, In Vitro and In Vivo Studies Pharmaceuticals <i>Datura innoxia</i> daturaolone terpenoid anti-inflammatory NF-<i>κ</i>B nitric oxide |
| title | Anti-Inflammatory Potential of Daturaolone from <i>Datura innoxia</i> Mill.: In Silico, In Vitro and In Vivo Studies |
| title_full | Anti-Inflammatory Potential of Daturaolone from <i>Datura innoxia</i> Mill.: In Silico, In Vitro and In Vivo Studies |
| title_fullStr | Anti-Inflammatory Potential of Daturaolone from <i>Datura innoxia</i> Mill.: In Silico, In Vitro and In Vivo Studies |
| title_full_unstemmed | Anti-Inflammatory Potential of Daturaolone from <i>Datura innoxia</i> Mill.: In Silico, In Vitro and In Vivo Studies |
| title_short | Anti-Inflammatory Potential of Daturaolone from <i>Datura innoxia</i> Mill.: In Silico, In Vitro and In Vivo Studies |
| title_sort | anti inflammatory potential of daturaolone from i datura innoxia i mill in silico in vitro and in vivo studies |
| topic | <i>Datura innoxia</i> daturaolone terpenoid anti-inflammatory NF-<i>κ</i>B nitric oxide |
| url | https://www.mdpi.com/1424-8247/14/12/1248 |
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