Studies On Anti-Inflammatory, Analgesic And Anti-Inflammatory Mechanism Effects Of Ia And A_cO-IA

[Abstract] Objective: To evaluate the anti-inflammatory , analgesic effects , acute toxicity, the stimulation of gastrointestinal in mice and anti-inflammatory mechanism of Ilicifolius alkaloids A and its derivatives Acetyl Ilicifolius alkaloids A. Methods: The anti-inflammatory effect was observed by mouse auricle swelling test induced by xylene;analgesic effects was observed by mouse the pain threshold caused by hot-Plate test and mouse aceticacid-induced twisting test;The influence of the detervatives upon the mice coagulation-time and bleeding-time were tested with the capillary method and measuring by cutting the tail of mice. The modified Karber method was used to determine LD50 of Ilicifolius alkaloids A and its derivatives Acetyl Ilicifolius alkaloids A;to observe the stimulation of gastrointestinal in mice by continuous intragastric administration.After stimulating the lood sample of healthy volunteer with calcium ionophore A23187, concentration of thromboxane B2(TXB2) in the health volunteer,s blood was detected by enzyme-linked immunosorbent assay (ELISA) to observe the effects of IA and ACO-IA at low-and high-dose on the activity of COX-1, with aspirin as control drug.The concentration of prostaglandin I2 (PGI2) in the healthy volunteer,s blood sample, in which aspirin was added to destroy activity of COX-1 beforehand with lipopolysaccharide, was detected by ELISA mentod to observe effects of IA and ACO-IA at low-and high-dose on the activity of COX-2 with celecoxib as control drug. Results: The LD50 of IA in mice was 2198.87mg/kg , 95% confidence interval (CI) was 1690.68mg/kg～2544.46mg/kg and LD50 of ACO-IA in mice was 2009.43mg/kg, 95% confidence interval (CI) was 1113.49mg/kg～2606.47mg/kg.NSAIDs' side effect on gastrointestinal was related to the inhibition of COX-1.The study of test about IA and ACO-IA showed that 2 doses (100mg/kg,50mg/kg) of gastric mucosal injury degree were less than the equal dose of aspirin(100mg/kg).Moreover,the differences were significant(p<0.05,p<0.01).IA and ACO-IA can significantly inhibit inflammatory pain in mice that caused by the acetic acid, and the inhibition of IA and ACO-IA were 69.41% and 68.04%, which is significant difference bettween control group and treatment group (p<0.01). The four-dose of IA and ACO-IA evidently suppressing the mouse ear edema induced by dimethylbenzene,and the effect of middle-dose was similar to that of aspirin,but none of two derivative exhibited significant analgesic activities in hot-plate test.It was showed that IA and ACO-IA can prolong blood coagulation time in mice through capillary and tail-cutting methods. The human whole belood analysis test show that IA and ACO-IA can reduce elevated levels of PGI2, which demonstrated selective inhibition of COX-2 activity.Conclusion: By the grading standard of toxicity, the two compounds belong to the low toxicity of drugs. They have analgesic and anti-inflammatory effect, and are able to reduce mouse gastric mucosal damage. IA and ACO-IA can reduce the releasing of inflammatory mediators ,such as PGI2,by inhibiting the activities of COX-2.