دورية أكاديمية
Combinative effects of akarkara root-derived metabolites on anti-inflammatory and anti-alzheimer key enzymes: integrating bioassay-guided fractionation, GC-MS analysis, and in silico studies.
العنوان: | Combinative effects of akarkara root-derived metabolites on anti-inflammatory and anti-alzheimer key enzymes: integrating bioassay-guided fractionation, GC-MS analysis, and in silico studies. |
---|---|
المؤلفون: | Ibrahim RM; Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Ainy Street, Cairo, 11562, Egypt., Abdel-Baki PM; Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Ainy Street, Cairo, 11562, Egypt. passent.mohamed@pharma.cu.edu.eg., Elmasry GF; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt. ghada.elmasry@pharma.cu.edu.eg., El-Rashedy AA; Natural and Microbial Products Department, National Research Center (NRC), Dokki, Giza, 12622, Egypt., Mahdy NE; Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Ainy Street, Cairo, 11562, Egypt. |
المصدر: | BMC complementary medicine and therapies [BMC Complement Med Ther] 2023 Nov 17; Vol. 23 (1), pp. 413. Date of Electronic Publication: 2023 Nov 17. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101761232 Publication Model: Electronic Cited Medium: Internet ISSN: 2662-7671 (Electronic) Linking ISSN: 26627671 NLM ISO Abbreviation: BMC Complement Med Ther Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central, [2020]- |
مواضيع طبية MeSH: | Antioxidants*/chemistry , Acetylcholinesterase*, Molecular Docking Simulation ; Gas Chromatography-Mass Spectrometry ; Cyclooxygenase 2/metabolism ; Methylene Chloride ; Plant Extracts/chemistry ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/chemistry ; Anti-Bacterial Agents ; Biological Assay ; Cholinergic Antagonists |
مستخلص: | Background: Anacyclus pyrethrum L. (Akarkara root), a valuable Ayurvedic remedy, is reported to exhibit various pharmacological activities. Akarkara root was subjected to bioassay-guided fractionation, to isolate its active constituents and discover their potential bioactivities, followed by computational analysis. Methods: The methanol extract and its fractions, methylene chloride, and butanol, were assessed for their antioxidant, anti-inflammatory, and anticholinergic potentials. The antioxidant activity was determined using DPPH, ABTS, FRAP, and ORAC assays. The in vitro anticholinergic effect was evaluated via acetyl- and butyryl-cholinesterase inhibition, while anti-inflammatory effect weas determined using COX-2 and 5-LOX inhibitory assays. The methylene chloride fraction was subjected to GC/MS analysis and chromatographic fractionation to isolate its major compounds. The inhibitory effect on iNOS and various inflammatory mediators in LPS-activated RAW 264.7 macrophages was investigated. In silico computational analyses (molecular docking, ADME, BBB permeability prediction, and molecular dynamics) were performed. Results: Forty-one compounds were identified and quantified and the major compounds, namely, oleamide (A1), stigmasterol (A2), 2E,4E-deca-2,4-dienoic acid 2-phenylethyl amide (A3), and pellitorine (A4) were isolated from the methylene chloride fraction, the most active in all assays. All compounds showed significant in vitro antioxidant, anticholinergic and anti-inflammatory effects. They inhibited the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in activated RAW macrophages. The isolated compounds showed good fitting in the active sites of acetylcholinesterase and COX-2 with high docking scores. The ADME study revealed proper pharmacokinetics and drug likeness properties for the isolated compounds. The isolated compounds demonstrated high ability to cross the BBB and penetrate the CNS with values ranging from 1.596 to -1.651 in comparison with Donepezil (-1.464). Molecular dynamics simulation revealed stable conformations and binding patterns of the isolated compounds with the active sites of COX-2 and acetyl cholinesterase. Conclusions: Ultimately, our results specify Akarkara compounds as promising candidates for the treatment of inflammatory and neurodegenerative diseases. (© 2023. The Author(s).) |
References: | Eur J Med Chem. 2016 Nov 10;123:282-297. (PMID: 27484514) J Med Chem. 2012 Nov 26;55(22):10282-6. (PMID: 23035744) J Ethnopharmacol. 2021 Dec 5;281:114491. (PMID: 34364970) Biology (Basel). 2022 Feb 14;11(2):. (PMID: 35205173) Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26. (PMID: 11259830) Phytomedicine. 1997 Dec;4(4):331-4. (PMID: 23195583) Cell Biochem Biophys. 2018 Sep;76(3):345-356. (PMID: 30073572) Plants (Basel). 2021 Jan 13;10(1):. (PMID: 33451098) Food Chem. 2023 Jan 15;399:133948. (PMID: 35994855) Alzheimers Res Ther. 2012 Jun 29;4(3):22. (PMID: 22747839) Molecules. 2020 Nov 23;25(22):. (PMID: 33238392) J Chromatogr A. 2001 Jul 13;922(1-2):225-33. (PMID: 11486867) Foods. 2019 Nov 16;8(11):. (PMID: 31744147) Biotechniques. 2011 Feb;50(2):98-115. (PMID: 21486251) J Ethnopharmacol. 2023 Oct 5;314:116631. (PMID: 37172920) Rev Neurol (Paris). 2019 Dec;175(10):724-741. (PMID: 31521398) J Med Chem. 2015 May 14;58(9):4066-72. (PMID: 25860834) Bioorg Chem. 2020 May;98:103711. (PMID: 32179282) Sultan Qaboos Univ Med J. 2012 Feb;12(1):5-18. (PMID: 22375253) Molecules. 2017 May 12;22(5):. (PMID: 28498323) Int Immunopharmacol. 2018 Mar;56:179-185. (PMID: 29414648) Plant Foods Hum Nutr. 2023 Jun;78(2):383-389. (PMID: 37219720) J Natl Cancer Inst Monogr. 1992;(12):125-32. (PMID: 1616796) Br Med Bull. 1993 Jul;49(3):523-44. (PMID: 8221020) Plants (Basel). 2022 Sep 30;11(19):. (PMID: 36235444) Front Pharmacol. 2017 Sep 05;8:598. (PMID: 28928658) Vet World. 2021 Feb;14(2):457-467. (PMID: 33776312) Biomolecules. 2022 Oct 06;12(10):. (PMID: 36291639) Mar Drugs. 2022 Jan 06;20(1):. (PMID: 35049912) Curr Neuropharmacol. 2013 May;11(3):315-35. (PMID: 24179466) Rev Bras Farmacogn. 2020;30(5):622-640. (PMID: 33071385) Neurochem Res. 2013 Mar;38(3):547-56. (PMID: 23242789) J Neurol Sci. 2017 May 15;376:242-254. (PMID: 28431620) Phytother Res. 2013 Jan;27(1):99-106. (PMID: 22473789) An Acad Bras Cienc. 2016 Oct-Dec;88(4):2229-2237. (PMID: 27991959) Planta Med. 2012 Nov;78(16):1787-95. (PMID: 23047251) J Chem Inf Model. 2017 Dec 26;57(12):2911-2937. (PMID: 29243483) Bioorg Med Chem Lett. 2010 Dec 1;20(23):7159-63. (PMID: 20709553) Bioorg Chem. 2019 Aug;89:103007. (PMID: 31132600) BMC Complement Altern Med. 2010 Dec 16;10:77. (PMID: 21159207) Front Mol Neurosci. 2011 Sep 14;4:19. (PMID: 21949501) Adv Nutr. 2016 Sep 15;7(5):905-16. (PMID: 27633106) Environ Sci Pollut Res Int. 2022 Aug;29(39):59930-59947. (PMID: 35397021) Phytother Res. 2022 Apr;36(4):1459-1506. (PMID: 35229374) Immunol Rev. 2023 Aug;317(1):95-112. (PMID: 36815685) Eur J Med Chem. 2020 Feb 1;187:111916. (PMID: 31812794) |
فهرسة مساهمة: | Keywords: ADME; Akarkara root; Anti-inflammatory; Anticholinergic; GC-MS; Molecular docking |
المشرفين على المادة: | 0 (Antioxidants) EC 3.1.1.7 (Acetylcholinesterase) EC 1.14.99.1 (Cyclooxygenase 2) 588X2YUY0A (Methylene Chloride) 0 (Plant Extracts) 0 (Anti-Inflammatory Agents) 0 (Anti-Bacterial Agents) 0 (Cholinergic Antagonists) |
تواريخ الأحداث: | Date Created: 20231118 Date Completed: 20231127 Latest Revision: 20231127 |
رمز التحديث: | 20231127 |
مُعرف محوري في PubMed: | PMC10655324 |
DOI: | 10.1186/s12906-023-04210-6 |
PMID: | 37978514 |
قاعدة البيانات: | MEDLINE |
كن أول من يترك تعليقا!