title: Vitexin inhibits inflammatory pain in mice by targeting TRPV1, oxidative stress, and cytokines.
abstract: The flavonoid vitexin (1) is a flavone C-glycoside (apigenin-8-C-β-D-glucopyranoside) present in several medicinal and other plants. Plant extracts containing 1 are reported to possess antinociceptive, anti-inflammatory, and antioxidant activities. However, the only evidence that 1 exhibits antinociceptive activity was demonstrated in the acetic acid-induced writhing model. Therefore, the analgesic effects and mechanisms of 1 were evaluated. In the present investigation, intraperitoneal treatment with 1 dose-dependently inhibited acetic acid-induced writhing. Furthermore, treatment with 1 also inhibited pain-like behavior induced by phenyl-p-benzoquinone, complete Freund's adjuvant (CFA), capsaicin (an agonist of transient receptor potential vanilloid 1, TRPV1), and both phases of the formalin test. It was also observed that inhibition of carrageenan-, capsaicin-, and chronic CFA-induced mechanical and thermal hyperalgesia occurred. Regarding the antinociceptive mechanisms of 1, it prevented the decrease of reduced glutathione levels, ferric-reducing ability potential, and free-radical scavenger ability, inhibited the production of hyperalgesic cytokines such as TNF-α, IL-1β, IL-6, and IL-33, and up-regulated the levels of the anti-hyperalgesic cytokine IL-10. These results demonstrate that 1 exhibits an analgesic effect in a variety of inflammatory pain models by targeting TRPV1 and oxidative stress and by modulating cytokine production.
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057970 Londrina, Brazil.
authors.forename: Sergio M
authors.initials: SM
authors.lastname: Borghi
authors.forename: Thacyana T
authors.initials: TT
authors.lastname: Carvalho
authors.forename: Larissa
authors.initials: L
authors.lastname: Staurengo-Ferrari
authors.forename: Miriam S N
authors.initials: MS
authors.lastname: Hohmann
authors.forename: Phileno
authors.initials: P
authors.lastname: Pinge-Filho
authors.forename: Rubia
authors.initials: R
authors.lastname: Casagrande
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D047310:Apigenin / Q000494:pharmacology* / Q000627:therapeutic use; D016227:Benzoquinones; D002211:Capsaicin / Q000009:adverse effects / Q000627:therapeutic use; D002351:Carrageenan / Q000009:adverse effects / Q000627:therapeutic use; D016207:Cytokines / Q000009:adverse effects / Q000096:biosynthesis / Q000627:therapeutic use; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000494:pharmacology; D006027:Glycosides / Q000009:adverse effects / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D050916:TRPV Cation Channels / Q000187:drug effects*
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D016227:Benzoquinones; D016207:Cytokines; D006027:Glycosides; D010936:Plant Extracts; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C561801:apigenin-8-C-beta-D-glucopyranoside; C029322:phenylbenzoquinone; D047310:Apigenin; D002351:Carrageenan; D005620:Freund's Adjuvant; C032731:vitexin; D002211:Capsaicin