RETRACTED ARTICLE: Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice

Abstract

Background Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain. Methods The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freund’s Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes. Results Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model. Conclusion The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.

Poncirin attenuates CCL4-induced liver injury through inhibition of oxidative stress and inflammatory cytokines in mice

“…All the animals experiments were performed in the Quaid-i-Azam University Islamabad, Pakistan (Department of Pharmacy, Faculty of biological sciences) pathogen free area (BEC-FBS-QAU2018-90) according to the guidelines issued for the experimental purposes by Quaid-i-Azam University, Islamabad,. The temperature was maintained at 23 ± 0.5°C, with 12 h light/dark cycle and free excess to water and food [16,17]. All the animals used in the present study were of healthy nature and no abnormalities/pathology was observed [16,17].…”

“…The temperature was maintained at 23 ± 0.5°C, with 12 h light/dark cycle and free excess to water and food [16,17]. All the animals used in the present study were of healthy nature and no abnormalities/pathology was observed [16,17].…”

Leaves Aqueous Extract of <i>Boerhavia coccinea</i> Induces Antinociceptive Effect but Increases Nitric Oxide Production in Macrophages

“…Its intraplantar injection produces a distinct two-phase response. The first phase called neurogenic or non-inflammatory pain results from immediate activation nociceptive receptors including transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vaniloid 1 (TRPV1) [16] [17] [18]. In this early phase of formalin-induced pain behavior, surface nociceptors can also be activated by the bradykinin, serotonin and substances released by resident cells.…”

Flavonoids from Aurantii Fructus Immaturus and Aurantii Fructus: promising phytomedicines for the treatment of liver diseases

“…Findings suggest that poncirin treatment attenuates extrinsic pathway-mediated apoptosis, possibly making it a hepatoprotective agent against toxins. It has also been reported that poncirin (30 mg/kg) significantly attenuates hepatic inflammation and liver injury in complete freund’s adjuvant (CFA)-induced pain mouse model by inhibiting the production of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, and enhancing the activation of anti-oxidant pathways including Nrf2 and HO-1 [ 141 ]. Park et al reported that narirutin alleviated alcohol-induced liver damage in mice through the prevention of lipid droplet formation, inhibition of NF-κB pathways, and suppression of pro-inflammatory cytokines, TNF-α and IL-1β [ 142 ].…”