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The Modeling And Screening Study Of The Anti-inflammation Traditional Chinese Medicines With AA System And T Cell

Posted on:2006-11-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:L LinFull Text:PDF
GTID:1104360152988574Subject:traditional Chinese medicine chemistry
Abstract/Summary:PDF Full Text Request
Inflammation is a common and important pathologic process. It could occur in any part of the body and is related with many kinds of diseases. Inflammation is also a kind of important protective response of the body. Were there no inflammation response, the infection can not be controlled, the damaging of the organ and the tissue will be continued. It is to say that human being can not living without infection response. Infection reaction may injury the body to a certain extent. For instance, anaphylaxis of drug and poison may endanger the life of the sicker. Acute inflammatory dropsy in laryngeal may induce asphyxiation. Inflammation of brain or meninges can oppress the life nerve centre. Serious cardiac muscle inflammation can affect the heart function. So it is important to develop some drugs to prevent or control the inflammatory injury. In the current market there are still no ideal drugs for some kind of chronic andimmunity inflammation such as atrophic arthritis, nephritis, asthma and so on. Steroidalanti-inflammatory drugs have affirmative effect, its serious side effect such as hormoneturbulence, plenilune face, osteoporosis had restricted its application. Cytotoxic immunityinhibitors have serious toxicity and could not be accepted by the patients. Some immunityregulators and inflammation factors including receptor antagonism and gene treated drugsare too expensive to be afforded. Although the traditional non-steridal anti-inflammatorydrugs have good effect on the inflammation t the side effect of stomach blooding andkidney injury is too serious. Now scientists have developed a series of new NSAIDs thattarget to COX and 5-LOX. Experiment approved that those new drugs have better effect oninflammation and fewer side effects. The latency toxic and side effect of these drugs stillshould be studied. Considering of the disadvantages many investigators begin to look upto the natural resource to screen the anti-inflammation drugs in vitro models. The plant kingdom is hitherto a practically unexplored resource of anti-inflammationdrugs. In China, there are a lot of TCMs being used to treat inflammation. While there is nota set of HTS platform with multi-targets in vitro for anti-inflammation drugs screeing, theaim of this thesis is to develop a kind of simple, quick and economic HTS method andscreen some TCMs.1. Development of 5-LOX anti-inflammation model in vitro A kind of 5-LOX anti-inflammation model in vitro was developed and optimized. NDGAwas used to validate the model's reliability and stablility. 17 TCMs and 14800 samples weretested by using this model. Seven of the seventeen TCMs tested showed moderate orstrong inhibition ability. Shamoga (herb) who showed the strongest inhibition ability duringthe sample library is 82.76%. A further research was carried out with the Xiehe samplelibrary (inhibition, >70%). Results showed that 40 samples have a good dose-effectrelationship and the hits was 0.27%.2. Optimizing of the COX-2/COX-1 anti-inflammation model in vitro COX-1 was prepared from the fresh bovine seminal vesicles and was determined bySDS-PAGE and Bradform method. The COX activity assay kit was used to measure theperoxidase activity of cyclooxygenase. The peroxidase activity is assayed colorimetricallyby monitoring the appearance of oxidized TMPD. Special inhibitor such as SC-560 (COX-1inhibitor) and Nimesulide (COX-2 inhibitor) had been used to test themodel and showed asatisfied result. Seventeen TCMs were tested by this model. Among the samples onlyDacheqianzi showed a moderate inhibition with the COX-1 model, three kinds of TCMsshowed a moderate inhibiton with the COX-2 model. They were Shahao, Dacheqianzi andXixiancao.3. Development of the mouse T lymphocyte anti-inflammation model in vitro The spleen was breaked away from the mouse with asepsis and made to single cellsuspended solution. Proliferation of the mouse T lymphocyte was stimulated with Con A.An optimal method for assessing T lymphocytic proliferation effect by MTT colorimetricassay was developed. CHX and some TCMs were tested by this...
Keywords/Search Tags:anti-inflammation, COX, 5-LOX, T lymphocyte, HTS, Shamoga
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