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Study On The Effect Of Dendrobium Huoshanense Grown In Three Modes On The Expression Of CYP450 Enzymes In The Liver Of Mice And The Differences In Its Protective Effects On Liver Injury

Posted on:2020-10-18Degree:MasterType:Thesis
Country:ChinaCandidate:W LiuFull Text:PDF
GTID:2434330596496956Subject:Pharmacy
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Dendrobium is a valuable Chinese herbal medicine with a long history.D.huoshanenese is the finest of Dendrobium,which has the functions of protecting the liver and stomach,strengthening immunity,anti-oxidation,anti-tumor,anti-cataract and a variety of biological activities such as lowering blood glucose.However,the effects of different planting methods on the pharmacological effects of Dendrobium have not been reported.In this study,the effects of D.huoshanenese planted in different ways on cytochrome P450 enzyme expression were studied by western blot analysis using wild growth mode planting,under the forest planting and greenhouse cultivation of D.huoshanenese.Three liver injury models including CCl4 liver injury,acetaminophen(APAP)liver injury and cyclophosphamide liver injury were established to study the differences in hepatoprotective activities of D.huoshanenese,providing a basis for the industrial development,clinical safety and rational use of D.huoshanenese.The mainly research contents and conclusions are as follows:1.The protective effects of D.huoshanenese planting in three different ways on acute liver injury induced by carbon tetrachloride.A classic CCl4 liver injury model was used to evaluate the hepatoprotective activity of D.huoshanenese planting in three different ways.The results showed that the high and low doses of Dendrobium can reduce the levels of alanine aminotransferase(ALT)and alanine aminotransferase(AST)in serum,increase the activity of superoxide dismutase(SOD)and inhibit malondialdehyde(MDA)The hepatoprotective effects of D.huoshanenese planted in different ways were different.The wild growth mode planting and under the forest planting of D.huoshanenese was better in liver protection,but the effect of D.huoshanenese planted under the forest was the best.2.The protective effects of D.huoshanenese planting in three different ways on acute liver injury induced by acetaminophen.APAP is an analgesic antipyretic and anti-inflammatory drug commonly used in clinical practice,but long-term use,combination or large dose of drugs can cause liver toxicity,even acute liver failure,and its damage mechanism is related to the irreversible binding of metabolites to macromolecules.This chapter establishes the APAP liver injury model to evaluate the hepatoprotective activity of D.huoshanenese planting in three different ways in different mechanisms.The results showed that D.huoshanenese obtained from three different planting methods could inhibit the increase of ALT,AST and MDA,and increase the activity of SOD and glutathione(GSH)in the liver of mice.Among them,D.huoshanenese,which was planted in wild growth mode and under the forest,had better hepatoprotective activity in mice to the APAP-induced liver injury,but the effect of D.huoshanenese planting under the forest was the best.3.The protective effects of D.huoshanenese planting in three different ways on liver injury induced by cyclophosphamide.Cyclophosphamide is the most commonly used immunosuppressant and antitumor drug for the treatment of malignant tumors.It is also a representative agent for alkylating agents and has a broad-spectrum anti-cancer effect.However,because it is a non-cell cycle-specific drug,intermediate metabolites also damage normal cell DNA and induce the production of a large number of toxic radicals.The cyclophosphamide liver injury model was used to further evaluate the D.huoshanenese planting in three different ways.The experimental results show that D.huoshanenese planted in three different ways can reduce the content of ALT and AST and increase the activity of SOD in liver of mice.However,only the D.huoshanenese planting in wild growth mode can significantly inhibit the increase of MDA activity,which may be related to the fact that some of the components of it are higher than that of the other Dendrobium planting under the forest and greenhouse,but further research is needed.4.Effects of D.huoshanenese planting in three different ways on the expression of major cytochrome P450 enzymes in mouse liver.Previous studies by our group showed that D.huoshanenese had no toxic effects on mice.Western blot was used to study the effects of D.huoshanenese planting in three different ways on the expression of five major cytochrome P450 enzymes,including CYP1A2,CYP2 B,CYP2C19,CYP2E1 and CYP3 A.The results of Western blot showed that the D.huoshanenese planting in wild growth mode had a significant dose-dependent induction of CYP1A2 and CYP3 A,and the high dose group significantly induced CYP2 B.The high-dose group of D.huoshanenese planted under the forest had significant induction of CYP1A2 and CYP2 B,while the low dose group had no significant Induction.D.huoshanenese planted in greenhouses induced a significant dose-dependent induction of CYP1A2 and CYP2B.
Keywords/Search Tags:D. huoshanenese, cytochrome P450, carbon tetrachloride, acetaminophen, cyclophosphamide
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