دورية أكاديمية
أعرض في EDS

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.

التفاصيل البيبلوغرافية
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).)
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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
الوصف
تدمد:2662-7671
DOI:10.1186/s12906-023-04210-6