Abstract
Fibromyalgia is a potentially disabling idiopathic disease characterized by widespread chronic pain associated with comorbidities such as fatigue, anxiety, and depression. Current therapeutic approaches present adverse effects that limit adherence to therapy. Diosmetin, an aglycone of the flavonoid glycoside diosmin found in citrus fruits and the leaves of Olea europaea L., has antinociceptive, anti-inflammatory, and antioxidant properties. Here, we investigated the effect of diosmetin on nociceptive behaviors and comorbidities in an experimental fibromyalgia model induced by reserpine in mice. To induce the experimental fibromyalgia model, a protocol of subcutaneous injections of reserpine (1 mg/kg) was used once a day for three consecutive days in adult male Swiss mice. Mice received oral diosmetin on the fourth day after the first reserpine injection. Nociceptive (mechanical allodynia, muscle strength, and thermal hyperalgesia) and comorbid (depressive-like and anxiety behavior) parameters were evaluated. Potential adverse effects associated with diosmetin plus reserpine (locomotor alteration, cataleptic behavior, and body weight and temperature changes) were also evaluated. Oral diosmetin (0.015–1.5 mg/kg) reduced the mechanical allodynia, thermal hyperalgesia, and loss of muscle strength induced by reserpine. Diosmetin (0.15 mg/kg) also attenuated depressive-like and anxiety behaviors without causing locomotor alteration, cataleptic behavior, and alteration in weight and body temperature of mice. Overall, diosmetin can be an effective and safe therapeutic alternative to treat fibromyalgia symptoms, such as pain, depression and anxiety.
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Abbreviations
- B1:
-
Baseline 1
- B2:
-
Baseline 2
- DMSO:
-
Dimethylsulfoxide
- I max :
-
Maximum inhibition
- Nrf2:
-
Nuclear factor erythroid 2-related factor 2
- NF-κB:
-
Nuclear factor kappa B
- Keap1:
-
Kelch-like epichlorohydrin-associated protein 1
- p62:
-
Ubiquitin-binding protein p62
- PWT:
-
Paw withdrawal threshold
- SIRT1:
-
Silent information regulator 1
- TRPV1:
-
Transient potential vanilloid receptor subtype 1
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Acknowledgements
We thank the Program in Biological Sciences: Toxicological Biochemistry of the Federal University of Santa Maria, and we thank the Federal University of Santa Maria. We thank you for the financial support given by FAPERGS, CAPES/PROEX, and CNPq. We thank CNPq, PIBITI/CNPq, CAPES/PROEX and PROBIC/FAPERGS for their fellowship support.
Funding
Funding support for this project was provided in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001; by the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul-FAPERGS (Grant #21/2551–0001966-2) (Brazil); and by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). CAPES/Programa de Excelência Acadêmica (PROEX) (process #88881.844988/2023-01, Grant #1333/2023). This study is part of the National Institute of Science and Technology in 3D printing and Advanced Materials Applied to Human and Veterinary Health (INCT_3D-Saúde) funded by CNPq, Brazil (grant #406436/2022–3). S.M.O. and D.B.R. are recipient of fellowship from CNPq (Grants #309404/2023–1 and #307690/2021–0, respectively). M.F.P.F. is recipient of fellowship from CAPES/PROEX (process #88882.182170/2018–01), L.P.M. is recipient of fellowship from Programa Institucional de Bolsas de Iniciação Científica (PROBIC)/FAPERGS, and A.F. is recipient of fellowship from Programa Institucional de Bolsas de Iniciação em Desenvolvimento Tecnológico e Inovação (PIBITI)/CNPq. We thank CNPq, PIBITI/CNPq, CAPES/PROEX and PROBIC/FAPERGS for their fellowship support.
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Participated in research design: [Lara P. Marquezin; Maria Fernanda P. Fialho; Sara M. Oliveira]. Conducted experiments: [Lara P. Marquezin; Maria Fernanda P. Fialho; Amanda Favarin; Jéssica D. Lara; Michele M. Pillat]. Performed data analysis: [Lara P. Marquezin; Maria Fernanda P. Fialho; Denis B. Rosemberg; Sara M. Oliveira]. Wrote or contributed to the writing of the manuscript: [Lara P. Marquezin; Maria Fernanda P. Fialho; Amanda Favarin; Jéssica D. Lara; Michele M. Pillat; Denis B. Rosemberg; Sara M. Oliveira]. All authors read and approved the final manuscript.
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Marquezin, L.P., Fialho, M.F.P., Favarin, A. et al. Diosmetin attenuates fibromyalgia-like symptoms in a reserpine-induced model in mice. Inflammopharmacol (2024). https://doi.org/10.1007/s10787-024-01473-4
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DOI: https://doi.org/10.1007/s10787-024-01473-4