Iridoids from Morinda lucida, (Benth.) Rubiaceae, produced analgesic and anti-inflammatory activities via agonism at the kappa and delta opioid receptors, inhibition of COX-2 besides elevation of CAT and SOD activities.

Autor: Kumatia EK; Department of Phytochemistry, Centre for Plant Medicine Research, Mampong-Akwapim. Ghana; Department of Quality Management, Centre for Plant Medicine Research, Mampong-Akwapim, Ghana. Electronic address: kofi2rhyme@yahoo.com., Ayertey F; Department of Phytochemistry, Centre for Plant Medicine Research, Mampong-Akwapim. Ghana., Ohta T; Department of Pharmacognosy, Faculty of Pharmaceutical Sciences. Nagasaki International University. Nagasaki 859-3298, Japan., Uto T; Department of Pharmacognosy, Faculty of Pharmaceutical Sciences. Nagasaki International University. Nagasaki 859-3298, Japan., Tung NH; Faculty of Pharmacy, Phenikaa University, Viet Nam.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2023 Jun 12; Vol. 309, pp. 116355. Date of Electronic Publication: 2023 Mar 11.
DOI: 10.1016/j.jep.2023.116355
Abstrakt: Ethnopharmacological Relevance: Pain and inflammation are the major symptoms of almost every human disease. Herbal preparations from Morinda lucida are used to treat pain and inflammation in traditional medicine. However, the analgesic and anti-inflammatory activities of some of the plant's chemical constituents are not known.
Aim of the Study: The aim of this study is to evaluate the analgesic and anti-inflammatory activities and possible mechanisms of these activities of iridoids from Morinda lucida.
Material and Methods: The compounds were isolated using column chromatography and characterized by NMR spectroscopy and LC-MS. Anti-inflammatory activity was evaluated using carrageenan-induced paw edema. Whereas, the analgesic activity was assessed in the hot plate and acetic acid-induced writhing assays. Mechanistic studies were conducted using pharmacological blockers, determination of antioxidant enzymes, lipid peroxidation, and docking studies.
Results: The iridoid, ML2-2 exhibited inverse dose-dependent anti-inflammatory activity (42.62% maximum at 2 mg/kg p. o). ML2-3 produced dose-dependent anti-inflammatory activity (64.52% maximum at 10 mg/kg p. o.). Anti-inflammatory activity of diclofenac sodium was 58.60% at 10 mg/kg p. o. Furthermore, ML2-2 and ML2-3 produced analgesic activity (P < 0.01) of 44.44 ± 5.84 and 54.18 ± 19.01%. at 10 mg/kg p. o. respectively in the hot plate assay and 64.88 and 67.44% in the writhing assay. ML2-2 significantly elevated catalase activity. However, ML2-3 elevated SOD and catalase activity significantly. In the docking studies, both iridoids formed stable crystal complexes with delta and kappa opioid receptors, and the COX-2 enzyme with very low free binding energies (ΔG) from -11.2 to -14.0 kcal/mol. However, they did not bind with the mu opioid receptor. The lower bound RMSD of most of the poses were found to be ≤ 2. Several amino acids were involved in the interactions through various inter molecular forces.
Conclusion: These results indicate that ML2-2 and ML2-3 possessed very significant analgesic and anti-inflammatory activities via acting as both delta and kappa opioid receptor agonist, elevation of anti-oxidant activity and inhibition of COX-2.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: