Diosmetin as a novel transient receptor potential vanilloid 1 antagonist with antinociceptive activity in mice
| Autor: | Sara Marchesan Oliveira, Yanka Oliveira Coelho, Gabriela Trevisan, Amanda Spring de Almeida, Mario F. C. Santos, Edinara da Silva Silveira, Rosana Casoti, Fernando Bellinaso, Gabriela de Oliveira Adamante, Flávia Karine Rigo, Camila Camponogara, Alessandra Marcone Milioli, Samira Dal-Toé De Prá, Juliano Ferreira, Alexandre Vinhal Desideri |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Resiniferatoxin Diosmin TRPV1 Pain TRPV Cation Channels Pharmacology 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Toxicity Tests medicine Animals General Pharmacology Toxicology and Pharmaceutics Pain Measurement Flavonoids Inflammation Analgesics Dose-Response Relationship Drug Antagonist General Medicine Diosmetin Disease Models Animal 030104 developmental biology Nociception Spinal Cord chemistry Mechanism of action Capsaicin Neuralgia Calcium Diterpenes medicine.symptom Synaptosomes medicine.drug |
| Zdroj: | Life Sciences. 216:215-226 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2018.11.029 |
| Popis: | Diosmetin is an O‑methylated flavone found naturally in citrus fruit, and it was identified in Amphilophium crucigerum (L.), a plant popularly used as an analgesic. This compound had different pharmacological effects and presented a chemical structure like the flavonoid eriodyctiol that exhibited antinociceptive effects by TRPV1 antagonism. However, the possible antinociceptive effect of this compound was not well documented. Thus, the goal of the present study was to evaluate the antinociceptive effect of diosmetin and its mechanism of action. The diosmetin effect on different pain models and its possible adverse effects were assessed on adult Swiss male mice (25–30 g). Mice spinal cord samples were used on calcium influx and binding assays using TRPV1 agonists. First, it was observed that the diosmetin reduced calcium influx mediated by capsaicin in synaptosomes and displace the specific binding to [3H]-resiniferatoxin in membrane fractions from the spinal cord of mice. Diosmetin (0.15 to 1.5 mg/kg, intragastric, i.g.) presented antinociceptive and antiedematogenic effect in the capsaicin intraplantar test and induced antinociception in a noxious heat test (48 °C). Also, treatment with diosmetin reduced mechanical and heat hypersensitivity observed in a model of inflammatory or neuropathic pain. Acute diosmetin administration in mice did not induce locomotor or body temperature changes, or cause liver enzyme abnormalities or alter renal function. Moreover, there were no observed changes in gastrointestinal transit or induction of ulcerogenic activity after diosmetin administration. In conclusion, our results support the antinociceptive properties of diosmetin which seems to occur via TRPV1 antagonist in mice. |
| Databáze: | OpenAIRE |
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