Flavonoids as Anti-Inflammatory and Analgesic Drugs: Mechanisms of Action and Perspectives in the Development of Pharmaceutical Forms

Verri, Waldiceu A.; Vicentini, Fabiana T. M. C.; Baracat, Marcela M.; Georgetti, Sandra R.; Cardoso, Renato D. R.; Cunha, Thiago M.; Ferreira, Sérgio Henrique; Cunha, Fernando Q.; Fonseca, Maria José Vieira; Casagrande, Rúbia

doi:10.1016/b978-0-444-53836-9.00026-8

Cited by 111 publications

(106 citation statements)

References 195 publications

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“…Inhibitory mechanisms of PDTC over NFkB not related to antioxidant activity include the interference with kB-dependent transactivation genes (Schreck et al, 1992), ability to translocate extracellular Zn 2þ to intracellular sites (Kim et al, 1999a;Lee et al, 2008), which has as a consequence the inhibition of NFkB activation (Bruck et al, 2002;Kim et al, 1999b), and inhibition of IkBeubiquitin ligase activity in cell-free system without extracellular stimuli-regulated production of reactive oxygen species (Hayakawa et al, 2003). Oxidative stress is an important component of pain and inflammation and treatment with antioxidants is able to reverse them (Maioli et al, 2015;Verri et al, 2012;Guazelli et al, 2013;Borghi et al, 2013). The hyperalgesic dose of jararhagin (1 mg/ paw) did not reduce the ferric reducing ability potential, the ability to scavenge the radical ABTS, and did not reduce the levels of reduced gluthathione between 0.5 and 7 h after its injection, which indicate a minor role for oxidative stress in jararhagin-induced mechanical hyperalgesia.…”

Section: Discussionmentioning

confidence: 98%

Jararhagin-induced mechanical hyperalgesia depends on TNF-α, IL-1β and NFκB in mice

Ferraz

Calixto-Campos

Manchope

et al. 2015

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Jararhagin is a hemorrhagic metalloprotease from Bothrops jararaca snake venom. The hyperalgesic mechanisms of jararhagin were investigated focusing on the role of proinflammatory cytokines (TNF-α and IL-1β) and the transcription factor NFκB. Intraplantar administration of jararhagin (1, 10, 100 and 1000 ng/paw) induced mechanical hyperalgesia, and increased TNF-α levels at 1, 3 and 5 h, and IL-1β levels at 0.5, 1 and 3 h after its injection in the paw tissue. Pre-treatment with morphine (2, 6, 12 μg/paw) inhibited jararhagin-induced mechanical hyperagesia. The systemic or local pre-treatment with etanercept (10 mg/kg and 100 μg/paw) and IL-1ra (30 mg/kg and 100 pg/paw) inhibited jararhagin-induced mechanical hyperalgesia. Co-administration of jararhagin (0.1 ng/paw) and TNF-α (0.1 pg/paw) or jararhagin (0.1 ng/paw) and IL-1β (1 pg/paw) enhanced the mechanical hyperalgesia. The systemic or local pre-treatment with PDTC (NFκB inhibitor; 100 mg/kg and 100 μg/paw) inhibited jararhagin-induced mechanical hyperalgesia as well as PDTC decreased the jararhagin-induced production of TNF-α and IL-1β. Thus, these data demonstrate the involvement of pro-inflammatory cytokines TNF-α and IL-1β and nuclear transcription factor NFκB in jararhagin-induced mechanical hyperalgesia indicating that targeting these mechanisms might contribute to reduce the pain induced by B. jararaca snake venom.

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Section: Discussionmentioning

confidence: 98%

Jararhagin-induced mechanical hyperalgesia depends on TNF-α, IL-1β and NFκB in mice

Ferraz

Calixto-Campos

Manchope

et al. 2015

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“…Statistical analysis was performed using analysis of variance followed by the Newman-Keuls test. oxidase (nicotinamide adenine dinucleotide phosphate oxidase), resulting in the production of superoxide anion, activation of NFκB, and, consequently, the production of cytokines [21,46,[49][50][51][52][53][54][55][56][57][58]. Therefore, this relationship between cytokines and oxidative stress explain the importance of oxidative stress in inflammation and hyperalgesia [55,58,59].…”

Section: Discussionmentioning

confidence: 98%

Riparin B, a Synthetic Compound Analogue of Riparin, Inhibits the Systemic Inflammatory Response and Oxidative Stress in Mice

et al. 2015

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The aim of our study was to evaluate the anti-inflammatory, anti-nociceptive, and anti-oxidant action of Riparin B in vivo. We performed experiments in which we induced paw edema by carrageenan and other mediators, carrageenan-induced peritonitis and the level of myeloperoxidase (MPO) activity, pro-inflammatory cytokines (TNF-α and IL-1β), malondialdehyde (MDA) acid, and glutathione (GSH) from the peritoneal fluid. We also performed behavior tests such as acetic acid-induced writhing, formalin-induced linking, and the hot plate test. Among the doses tested of the Riparin B (1, 3, and 10 mg/kg), the dose of 10 mg/kg showed the strongest effect, and this dose was able to reduce the paw edema induced by carrageenan, dextran, histamine serotonin, bradykinin, 48/80, and PGE2. Similarly, the Riparin B in the same dose reduced cell migration and significantly decreased the nociception induced by formalin and acetic acid and reversed the parameters of the oxidative stress. Thus, we can infer that Riparin B exhibits anti-inflammatory, anti-nociceptive, and anti-oxidant actions in vivo.

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“…These include caffeoylquinic acid derivatives, the flavonoid rutin, carotenes, diterpenoids, flavonoids, glycosides, saponins essential oils just to mention but few (Hirschmann, 1988;Tamura et al, 2009;da Silva et al, 2010). Several studies have demonstrated the anti-inflammatory, wound healing and antimicrobial effects of many of these compounds (de Paula et al, 1997;González et al, 2011;González-Gallego et al, 2010;Jin et al, 2010;Pan et al, 2010;Pelzer et al, 1998;Ríos and Recio, 2005;Verri Jr. et al, 2012).…”

Section: Phytochemical Studiesmentioning

confidence: 97%

Ethnobotanical study of medicinal plants by population of Valley of Juruena Region, Legal Amazon, Mato Grosso, Brazil

Bieski

Leonti

Arnason

et al. 2015

Journal of Ethnopharmacology

143

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Flavonoids as Anti-Inflammatory and Analgesic Drugs: Mechanisms of Action and Perspectives in the Development of Pharmaceutical Forms

Cited by 111 publications

References 195 publications

Jararhagin-induced mechanical hyperalgesia depends on TNF-α, IL-1β and NFκB in mice

Jararhagin-induced mechanical hyperalgesia depends on TNF-α, IL-1β and NFκB in mice

Riparin B, a Synthetic Compound Analogue of Riparin, Inhibits the Systemic Inflammatory Response and Oxidative Stress in Mice

Ethnobotanical study of medicinal plants by population of Valley of Juruena Region, Legal Amazon, Mato Grosso, Brazil

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