Protective effects of the flavonoid hesperidin methyl chalcone in inflammation and pain in mice: Role of TRPV1, oxidative stress, cytokines and NF-κB

Abstract

Cytokines and reactive oxygen species are inflammatory mediators that lead to increased sensitivity to painful stimuli, and their inhibition represents a therapeutic approach in controlling acute and chronic pain. The water-soluble flavonone hesperidin methyl chalcone (HMC) is used in the treatment of venous diseases, but its bioactivity as anti-inflammatory and analgesic is poorly understood. The present study evaluated the protective effects of HMC in widely used mouse models of acute and prolonged inflammation and pain. Male Swiss mice were treated with HMC (3-100 or 30 mg/kg, intraperitoneally) or vehicle (saline) 1h before inflammatory stimuli. In overt pain-like behavior tests, HMC inhibited acetic acid- and phenyl-p-benzoquinone-induced writhing, and capsaicin-, Complete Freund's Adjuvant (CFA)- and formalin-induced paw flinching and licking. HMC also inhibited carrageenan-, capsaicin- and CFA-induced mechanical and thermal hyperalgesia. Mechanistically, HMC inhibited carrageenan-induced cytokine (TNF-α, IL-1β, IL-6, and IL-10) production, oxidative stress and NF-κB activation. Furthermore, HMC did not cause gastric or hepatic injury in a 7 days treatment protocol. Thus, this is the first report that HMC reduces inflammation and inflammatory pain by targeting TRPV1 (transient receptor potential vanilloid type 1) receptor activity, oxidative stress, cytokine production, and NF-κB activity, which suggests its potential applicability in inflammatory diseases.

Ameliorative effect of hesperidin on ligation‐induced periodontitis in rats

“…Recently, the anti‐inflammatory effects of HES have also been examined in carrageenan‐induced mechanical and thermal hyperalgesia in a paw model of rats. In that study, HES inhibited the production of IL‐1β and IL‐6 and reduced the oxidative stress in the rat paw exudates . These limited findings in the current studies support and are consistent with results of the present investigation.…”

Superoxide anion-induced pain and inflammation depends on TNFα/TNFR1 signaling in mice

“…stimulus with KO 2 (30 µg, 25 µL) by the nitroblue tetrazolium (NBT) assay adapted to a microplate [18]. NBT reduction was measured at 600 nm (Multiskan GO, Thermo Scientific).…”

“…Furthermore, superoxide anion also contributes to pain and hyperalgesia [13,17]. In fact, superoxide anion up-regulates TNFR1 expression in nociceptive neurons and increases TNFα production [18,20]. It is not known, however, whether TNFα signaling represents a crucial step in pain transmission and hyperalgesia induced by superoxide anion.…”

Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice

“…After 5 min of incubation at room temperature, the absorbance was measured at 412 nm. A standard curve of GSH was performed (Pinho-Ribeiro et al 2015). Protein concentration was determined by the Lowry method (Lowry et al 1951).…”