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Studies on Anti-Inflammatory, Analgesic and Anti-Inflammatory Mechanism Effects of Ia and A_cO-IA

Author: WangZongYing
Tutor: LongShengJing
School: Guangxi Medical University
Course: Pharmacology
Keywords: Acanthus alkaloid A (IA) The acetyl A. ilicifolius alkaloid A (ACO-IA) Median lethal dose Anti-inflammatory Analgesic Gastric irritation Cyclooxygenase
CLC: R285.5
Type: Master's thesis
Year: 2011
Downloads: 86
Quote: 1
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Abstract


Objective: To study the the Acanthus alkaloid A (4 - hydroxyphenyl oxazole -2 - one ,4-hydroxy-2-benzoxazolone HBOA) English name: Ilicifolius alkaloids A (IA) and its derivatives acetyl Acanthus biological alkali A (4 - the acetoxy benzoxazole -2 - one ,4-Acetoxy-2-benzoxazolone referred to ACO-BOA) English name: Acetyl Ilicifolius alkaloids A (ACO-IA), anti-inflammatory and analgesic effects acute toxicity, gastrointestinal stimulation, and preliminary studies of its anti-inflammatory mechanism of action, both a good pharmacodynamic reduced toxicity, but also at least striving to find new anti-inflammatory drugs. Method: the improved Karber law in the mice LD50 observed toxic effects, using xylene-induced mouse ear edema, hot plate method in mice by intraperitoneal injection of acetic acid-induced writhing in mice to observe the anti-inflammatory and analgesic effects capillary method and tails observed two compounds on mice bleeding - blood clotting time, and observe the consecutive treatment of mouse gastrointestinal. Measured using in vitro human whole blood analysis methods in the study of the test of the anti-inflammatory mechanism in the Acanthus alkaloid A and its derivatives acetyl Acanthus A COX-1 and COX-2 activity. Extract the whole blood samples of healthy volunteers with calcium ionophore A23187 stimulation with aspirin is controlled by ELISA (enzyme-linked immunosorbent assay, ELISA) method to detect thromboxane B2 (thromboxane, TXB2) content to examine different concentration Acanthus alkaloids A and its derivatives acetyl Acanthus A; extraction volunteer whole blood COX-1 activity after aspirin inactivation of COX-1 after to lipopolysaccharide (lipopolysaccharide, LPS) stimulation, celecoxib cloth examine different concentration levels of prostacyclin I2 (postaglandinI2, PGI2) by ELISA Acanthus alkaloids A and its derivatives as control acetyl Acanthus A COX-2 activity affect the results: IA, half of the mice lethal dose that LD50 values ??2198.87mg/kg, 95% confidence interval from as 1690.68mg/kg to 2544.46mg/kg; the ACO-IA mice the LD50 value 2009.43mg/kg, its 95% confidence interval for the 1113.49mg/kg ~ 2606.47mg/kg. Gastrointestinal side effects of NSAIDs and its inhibition of COX-1. This study shows that the IA and the ACO-IA of 100mg/kg, 50mg/kg degree of gastric mucosal injury in both dose groups with the same dose of aspirin (100mg/kg) compared to less than aspirin, and the difference was significant (p lt; 0.05, p lt; 0.01). IA and ACO-IA intragastric administration significantly inhibited the inflammatory pain in mice caused by glacial acetic acid, two compounds of the high-dose group 400mg/kg pain inhibition rates were 69.41% and 68.04% CMC-Na control group compared to the highly significant difference (p lt; 0.01). The degree of swelling of mouse ear induced by xylene, IA and ACO-IA 4 dose groups could significantly inhibit the middle dose group (100mg/kg) inhibition similar to aspirin. From the mouse hot plate test results to see the role of the two compounds are basically no inhibition hot plate stimulus-induced pain response in mice. Capillary method and tails Determination clotting - bleeding time experiment, IA and ACO-IA, exhibit anticoagulant phenomenon, serve to extend the role of clotting and bleeding time. Human whole blood analysis of the experimental results show that IA and ACO-IA, effectively suppressed PGI2 increased whole blood, and a concentration-dependent manner. Expression or activity of COX-1 inhibition experiments, only a high concentration of ACO-IA group compared with the blank control group, the difference was significant (P lt; 0.05), inhibition of COX-1 activity or expression not very strong. Conclusion: The toxicity grading standard two compounds belonging to the low toxicity of the drug, and has anti-inflammatory and analgesic effects, can reduce the degree of damage of the gastric membrane. IA and ACO-IA, by inhibiting COX-2 activity, reducing the release of PGI2 inflammatory mediators.

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