Protective Effect of Cichorium Intybus Root Extract and Esculetin on Lipopolysaccharide-Induced Pain and Inflammation in Male Mice: A Potential Role for Tumor Necrosis Factor-α and Interleukin-1β

Abstract Lipopolysaccharide (LPS) has been widely used in animal modeling of inflammation-induced hyperalgesia. Proinflammatory cytokines (TNF-α, IL-1β) are involved in the pathogenesis of pain. Cichorium intybus (CI) contains many compounds which inhibit inflammatory mediators. The present study was designed to evaluate the effect of CI root hydro-alcoholic extract (CE) and Esculetin (ESC) - a bioactive coumarin compound of CI- on LPS-induced pain and inflammation in male mice. CE constituents were evaluated by GC-MS. Two different concentration of CE (300 and 500 mg/kg/p.o.) and ESC (40 mg/kg/i.p.,o.) were used for experiments. Drugs were administered once daily for 7 days. On day 7, LPS (0.83 mg/kg/i.p.) was injected 30 min after the last drug administration. Blood samples were collected 90 min after LPS injection. Hot plate and formalin tests were performed 24 hours after LPS injection. Serum TNF-α and IL-1β levels were measured using ELISA. LPS significantly increased the response time of animals in hot plate and both phases of formalin tests. CE (300 and 500 mg/kg/p.o.) significantly reduced the response time in comparison with the LPS group in hot plate and both phases of formalin tests. CE (500 mg/kg/p.o.) reduced serum TNF-α and IL-1β levels. Esculetin increased the response time in hot plate and the second phase of formalin test compared to the LPS group and also decreased IL-1β level, significantly. Our results demonstrated that CE exhibited anti-nociceptive and anti-inflammatory effects better than esculetin. The probable mechanism of anti-hyperalgesic effect of CE is related to inhibition of inflammatory cytokines IL-1β and TNF-α.