Novel insights into the molecular mechanisms underlying anti-nociceptive effect of myricitrin against reserpine-induced fibromyalgia model in rats: Implication of SIRT1 and miRNAs.

Autor: Aboutaleb AS; Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Allam A; Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Zaky HS; Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Harras MF; Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Farag FSA; Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Abdel-Sattar SA; Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt. Electronic address: sobeh2010@yahoo.com., El-Said NT; Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Ahmed HI; Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Abd El-Mordy FM; Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Dec 05; Vol. 335, pp. 118623. Date of Electronic Publication: 2024 Jul 24.
DOI: 10.1016/j.jep.2024.118623
Abstrakt: Ethnopharmacological Relevance: Manilkara zapota (L.) P. Royen, also termed sapodilla or chikoo, is a significant plant in ethnomedicine because of its long history of traditional medical applications. In diverse cultures, sapodilla is believed to protect against oxidative stress, inflammation, and some chronic diseases because of its high antioxidant content. The naturally occurring antioxidant myricitrin (MYR) flavonoid is primarily found in the leaves and other plant parts of sapodilla and it is well-known for having therapeutic qualities and possible health advantages.
Aim of the Study: To appraise the possible impact of MYR on a rat model of reserpine-induced fibromyalgia (FM) and explore its mechanism of action.
Materials and Methods: Isolation and identification of MYR with more than 99% purity from Manilkara zapota leaves were primarily done and confirmed through chromatographic and spectrophotometric techniques. To develop FM model, reserpine (RSP) was injected daily (1 mg/kg, s.c.) for three successive days. Then, MYR (10 mg/kg, i.p.) and pregabalin (PGB, 30 mg/kg, p.o.) were given daily for another five days. Behavioral changes were assessed through open field test (OFT), hot plate test, and forced swimming test (FST). Further analyses of different brain parameters and signaling pathways were performed to assess monoamines levels, oxidative stress, inflammatory response, apoptotic changes as well as silent information regulator 1 (SIRT1) and micro RNAs (miRNAs) expressions.
Results: From High-Performance Liquid Chromatography (HPLC) analysis, the methanol extract of sapodilla leaves contains 166.17 μg/ml of MYR. Results of behavioral tests showed a significant improvement in RSP-induced nociceptive stimulation, reduced locomotion and exploration and depressive-like behavior by MYR. Biochemical analyses showed that MYR significantly ameliorated the RSP-induced imbalance in brain monoamine neurotransmitters. In addition, MYR significantly attenuated oxidative stress elicited by RSP via up-regulating nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expressions, enhancing superoxide dismutase (SOD) and catalase (CAT) activities, and reducing malondialdehyde (MDA) content in brain. The RSP-provoked inflammatory response was also diminished by MYR treatment as shown by a significant decreased NOD-like receptor protein 3 (NLRP3) inflammasome expression along with reduced levels of interleukin 1 beta (IL-1β) and nuclear factor-κB (NF-κB). Furthermore, the anti-apoptotic activity of MYR was demonstrated by a marked rise in Bcl-2-associated X protein (BAX)/B cell lymphoma-2 (Bcl-2) ratio by lowering Bcl-2 while increasing BAX levels. In addition, MYR treatment significantly boosted the expression of SIRT1 deacetylase in RSP-treated animals. Interestingly, molecular docking showed the ability of MYR to form a stable complex in the binding site of SIRT1. Regarding miRNAs, MYR effectively ameliorated RSP-induced changes in miR-320 and miR-107 gene expressions.
Conclusion: Our findings afford new insights into the anti-nociceptive profile of MYR in the RSP-induced FM model in rats. The underlying mechanisms involved direct binding and activation of SIRT1 to influence different signaling cascades, including Nrf2 and NF-κB/NLRP3 together with modulation of miRNAs. However, more in-depth studies are needed before proposing MYR as a new clinically relevant drug in the management of FM.
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 © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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