Evaluation of analgesic and anti-inflammatory activities and molecular docking analysis of steroidal lactones from Datura stramonium L. |
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| Institution: | 1. School of Biotechnology, Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan 173 229, Himachal Pradesh, India;2. Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala 133 203, Haryana, India;3. Division of Natural Products Chemistry, Council of Scientific and Industrial Research-Indian Institute of Integrative Medicine, Jammu 180 001, Jammu and Kashmir, India;4. Pharmacokinetics-Pharmacodynamics, Toxicology and Formulation Division, Council of Scientific and Industrial Research-Indian Institute of Integrative Medicine, Jammu 180 001, Jammu and Kashmir, India;5. Department of Bioinformatics, Jaypee University of Information Technology, Waknaghat 173234, Himachal Pradesh, India;6. Lake Erie College of Osteopathic Medicine, Bradenton 34211, FL, USA;1. Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, 301617 Tianjin, China;2. Institute of TCM, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, 301617 Tianjin, China;1. Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China;2. Department of Pharmacy, Qingdao NO.6 People''s Hospital, Qingdao 266033, China;3. Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong 030619, China |
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| Abstract: | BackgroundDatura stramonium L. is widely used across the world for its therapeutic potential to treat inflammatory disorders. The current work was designed to isolate and identify steroidal lactones from D. stramonium leaves and evaluate their anti-inflammatory and analgesic properties.MethodsSeveral compounds were isolated from D. stramonium leaves and characterized by nuclear magnetic resonance and high-resonance electron spray ionization mass spectrometry techniques. Further, anti-inflammatory properties of these compounds were evaluated by in vitro assays, such as release of NO and pro-inflammatory cytokines by lipopolysaccharide (LPS)-activated J774A.1 macrophages. Using in vivo models, anti-inflammatory and analgesic effects were examined by mouse tail-flick, carrageenan-induced inflammation in rat paw model, vascular permeability in rats, and acetic acid-induced writhing in mice. The docking studies were performed for assessing the binding efficiency of the test compounds with cyclooxygenase-1 (COX-1) and COX-2, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), inducible nitric oxide synthases (iNOS) and nuclear factor-κB (NF-κB).ResultsThree lactones were isolated and confirmed as daturalactone (D1), 12-deoxywithastramonolide (D23), and daturilin (D27). Further, the isolated compounds showed nitric oxide inhibition and pro-inflammatory cytokines released by LPS-activated J774A.1 macrophages. The in vivo results suggest that D1, D23 and D27 (20 mg/kg) were able to reduce the pain and inflammation in various animal models. The docking analysis showed that these three compounds actively bind with COX-1, COX-2, LOX-1, NF-κB, and iNOS, validating the anti-inflammatory effects of the lactones.ConclusionThese findings demonstrate substantial anti-inflammatory and analgesic properties of D. stramonium-derived lactones and their potential as anti-inflammatory agents to treat chronic inflammatory ailments. |
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