Studies On The Effective Substances And Mechanism For Anti-CINV Of Ginger

Ginger is a traditional Chinese medicine which is used to treat vomit.For chemotherapy vomiting treatment,no matter whether acute or delayed emesis or vomiting,ginger was effecteive in treatment by using with other Chinese medicine.At the same time,fewer adverse reactions during the treat of CINV caused by ginger,also,ginger was quite cheap and easy to get.Therefore ginger was easy to be accepted by patients in clinically.Recent years,more and more foreign scholars pay attention on the anti-vomiting effects of ginger with the in-depth research on natural medicine.It has been demonstrated that the gastrointestinal tract to exert antiemetic effects could be effected by ginger.In many European and American countries,ginger has been used as a drug in the treatment for a variety causes of vomiting（such as motion vomiting,pregnancy vomiting）.But for the treatment for CINV,the foreigners prefer to use the western medicine,such as 5-HT3 receptor antagonists,cortisol,and other sub-thiazide.There are not so much reports about the ginger to treat such diseases in clinical which was related to the reason of Chinese medicine did not enter the international market,on the other hand,the most important reason is that the mechanism of the anti-CINV action of ginger has not been fully elucidated so far.In accordance with the theory and method of Chemical substances,the decoction was studied.In vivo animal model was applied,and the effective extractions were screened out.Mordern technology of analysis and separation was used,and the compounds was identified,screened with organ in vitro,Asisted with serum pharmacochemistry,verified by experiment in vivo,based on5-HT3 receptor,the effective substances in ginger were elucidated at last.The content and results of this paper were as follows:1.Research on the screening out the effective extraction in gingerThe systematic extraction and separation methods were used,and ginger was separated into three sections,the oils essentials,deposition,and upper-liquid.Pharmaceutical models in vivo were used,Gastric emptying in cisplatin-treated mice and pica mode of rats were applied to select the active anti-CINV extract of the three sections.The upper-liquid was the anti-CINV extraction in ginger.The composition of the upper-liquid was complex,so it was separated into two extractions:fat-soluble extraction（ginger ether extracts,GEE）and water-soluble extraction.The same pharmaceutical models in vivo were used,Gastric emptying in cisplatin-treated mice and pica mode of rats were applied to select the active anti-CINV extract of the two sections.GEE was the anti-CINV extractions in ginger.2.Research on the chemical compounds in gingerThe main components in GEE were detected by RP-HPLC and 6-gingerol、8-gingerol、6-shogaol、10-gingerol were detected.Meantime,the crude ginger from different habitats in China were detected with the same method,determination on the content of the 6-gingerol、8-gingerol、6-shogaol、10-gingerol in crude ginger,and the result showed that the content of 6-gingerol、8-gingerol、6-shogaol、10-gingerol were about 0.070%～0.12%、0.0050%～0.0099%、0.00070%～0.0024%、0.0047～0.0079%.Taking Shandong Tancheng as an example,the ratio of content was about 100:7:2:5.3.Studies on the Effective Substances for Anti-CINV of GingerGEE and the compatibility of 6-gingerol、8-gingerol、6-shogaol、10-gingerol（mix with the ratio in the formula）.With the experiments of the effect on kaolin and food consumption in cisplatin-treated rats,meantime the changes of related index components（SOD,MAO,5-HT,EGF,Gas）were also detected,and the result showed that the amount of Kaolin consumed by rats were declined significantly,the activity of SOD and MAO in the duodenum of rats and the contents of EGF and Gas in serum were improved,the content of 5-HT in duodenum and serum were decreased.Experimental results validated that the GEE was the effective part of the anti-CINV of ginger,also,it suggests that the compatibility of 6-gingerol、8-gingerol、6-shogaol、10-gingerol may be the effect material of the anti-CINV of ginger.4.Studies on the Mechanism for Anti-CINV of GingerThe antagonist effect of GEE and the four components（6-gingerol、8-gingerol、6-shogaol、10-gingerol）in it were explored by the contraction of guinea-pig ileum induced by SR57227A The results show that the maximum contraction of isolated guinea-pig ileum could be reduced by addition of GEE(2.3,4.6,11.5 mg·L^-1),6-gingerol,8-gingerol,10-gingerol or 6-shogaol(1,2,5μmol·L^-1)when the concentration of SR5727A was 10-5 mol·L^-1.With the same method,The antagonist effect of GEE and the four components（6-gingerol、8-gingerol、6-shogaol、10-gingerol）in it were explored by the contraction of guinea-pig ileum induced by carbachol,the results shou that the maximum contraction of isolated guinea-pig ileum could be reduced by addition of GEE(2.3,4.6,11.5 mg·L^-1),6-gingerol,8-gingerol,10-gingerol or 6-shogaol(1,2,5μmol·L^-1)when the concentration of carbachol was 10^-4 mol·L^-1.The conclusion is that 5-HT3 could be antagonized by GEE,6-gingerol,8-gingerol,10-gingerol and 6-shogaol.The antiemetic mechanism of ginger maybe related to it.At the same time,the research of M3 cholinergic receptor can provide the data basis for the follow-up study.