poncirin and Disease-Models--Animal

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.. 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.. 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.. 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.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Chronic Pain; Disease Models, Animal; Flavonoids; Formaldehyde; Hyperalgesia; Inflammation; Male; Mice; Mice, Inbred BALB C; Respiratory Hypersensitivity

The fruit of Poncirus trifoliate, which contains poncirin as a main constituent, is frequently used in the traditional Chinese medicine for inflammation, asthma, and infection diseases.. To examine anti-colitic effects of poncirin and ponciretin, a metabolite of poncirin by gut microbiota.. Colitis was induced in mice by the intrarectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Inflammatory markers were analyzed by enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, confocal microscopy, and flow cytometry. Peritoneal macrophages were isolated from mice stimulated with 4% thioglycolate.. Poncirin was metabolized to ponciretin in vitro and in vivo by gut microbiota of mice. Orally administered poncirin and ponciretin suppressed TNBS-induced colitis in mice: these inhibited colon shortening, myeloperoxidase activity, NF-κB activation, and Th17 cell differentiation, but increased occludin, claudin-1, and ZO-1 expressions and Treg cell differentiation. Poncirin and ponciretin suppressed the differentiation of splenocytes into Th17 cells and expression of IL-17 and Foxp3 in vitro, as well as the activation of macrophages stimulated with lipopolysaccharide (LPS) by inhibiting the binding of LPS on TLR4 of macrophages. These increased the differentiation of splenocytes into Treg cells. The ant-inflammatory effect of ponciretin was superior to that of poncirin.. Orally administered poncirin is metabolized to ponciretin by gut microbiota and poncirin and ponciretin attenuates colitis by suppressing NF-κB activation through the inhibition of LPS binding on macrophages and correcting Th17/Treg cell imbalance.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Bacteria; Biotransformation; Cells, Cultured; Colitis; Colon; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Flavonoids; Gastrointestinal Agents; Gastrointestinal Microbiome; Inflammation Mediators; Lipopolysaccharides; Macrophage Activation; Macrophages, Peritoneal; Male; Mice, Inbred C57BL; NF-kappa B; Signal Transduction; Spleen; T-Lymphocytes, Regulatory; Th17 Cells; Time Factors; Toll-Like Receptor 4; Trinitrobenzenesulfonic Acid