Self-micro Emulsification For Improving Bioavailability Of The Polyphenols From Sonchus Oleraceus Linn In Vivo And The Mechanism Of Absorption Enhancement

Sonchus oleraceus Linn(SOL)is rich in polyphenols.However,the polyphenols are poorly water-soluble,have poor stability in human cell culture fluid,and have low bioavailability.Therefore,it is necessary to use a means to improve its absorption and bioavailability.In this study,the polyphenols of SOL(SP)were used as the research object,and self-micro-emusifying drug delivery system(SMEDDS)was prapared to embed SP due to solve the deficiencies of it the main results and conclusions are as follows:1.The first part of the thesis showed that: the best prescription of the SMEDDS was as follows: Isopropylmyristate(IPM,oil): Tween-20(emulsifier): Polyethylent glycol-400(PEG-400,co-emulsifier)as 1:3:1(w/w/w).The emulsification grade of this SMEDDS was recorded as B grade,the drug load was 13% of the blank SMEDDS,the droplet of SP-SMEDDS was found to be uniform spherical,the particle size of the emulsion was(183 ± 0.7 nm)and the Zeta potential was(-11.78 ± 0.16 m V).SP-SMEDDS has low viscosity and good fluidity,and it could significantly improve the release rate of SP in vitro.These results showed that the SP-SMEDDS in this study has met the design requirements.2.The in vitro simulated digestion system was used to determine theantioxidant capacity of polyphenols,flavonoids,FRAP,DPPH,ABTS and ROAC in the sample after vitro digestion,and to detect the changes of active substances in SP by HPLC.And according to the changes of active substances in SP detected by HPLC,the changes of SP and SP-SMEDDS during digestion were discussed.The results showed that,during gastric digestion,the polyphenols and flavonoids of SP was slightly changed,these results explained by the fact that SP was affected by pepsin.During intestinal digestion,while the polyphenols and flavonoids as well as antioxidant capacity and the content of each active substance in SP were decreased significantly,these results indicated that the intestinal digestion had a tremendous impact on SP.On the other hand,SP-SMEDDS has no significant changes in polyphenols and flavonoids during the gastric digestive stage,in the intestinal digestion stage,the change trend of SP-SMEDDS was similar to SP,but the degree of change was less than SP,these results were indicated that SMEDDS could enhance the stability and accessibility of SP in the intestine digestion and can promote the abosorption of SP.3.Caco-2 cell model was established to further discuss the digestion and absorption of SP-SMEDDS in human intestines.The results showed that,the optimal uptake time was 60 minutes,the optimal uptake concentration was 100 ?g/m L,while SMEDDS could significantly increase the drug uptake and enhance drug bioavailability.Regarding theeffect of P-gp on the uptake of samples,only verapamil was involved in the process of chlorogenic acid ingestion.However,cyclosporin A has no significant effect on the uptake of chlorogenic acid and rutin.And then,transport mechanism of SP-SMEDDS was studied by using Caco-2 cell monolayer model,the effects of concentration,temperature and Verapamil on the transport of SP-SMEDDS were studied.It was known from the transport test,the transport amount of chlorogenic acid in Caco-2 cell was increased with increasing concentration,the Papp value of chlorogenic acid in Caco-2 cells was not affected by the drug concentration and transport temperature.Papp value(AP?BL)of SP-SMEDDS increased about 4 times compared with SP,so the way of chlorogenic acid transport was passive transcellular transport.After adding Verapamil,the efflux rate decreased,this indicated that SMEDDS could inhibit the efflux,enhance the bioavailability of SP,and means that chlorogenic acid has P-gp mediated efflux during passive diffusion.4.Established type 2 diabetic rat model to investigate the toxicity and absorbability of SP-SMEDDS in the body.Administration SP-SMEDDS for 4 weeks,and set SP group for comparison.After 4weeks,the results showed that,the appearance of the rats in the SP-SMEDDS group was improved,their glucose tolerance and blood lipid levels were better than SP group,levels of AST and ALT in the liver were significantly lower than SP group.SP-SMEDDS was improved thedegree of liver damage and increased the level of glycogen and the expression of p-GSK3? in the liver.In addition,the expression levels of AMPK and Akt in the SP-SMEDDS group were higher than those in the SP group.These results observed that SP-SMEDDS were more effective than SP,explained SMEDDS ccould increase absorption and bioavailability of SP in vivo,normalize hepatic insulin signal in the diabetic rat liver and reduce hepatic insulin resistance.Conclusion: SMEDDS improved the stability and accessibility of SP in the simulated gastrointestinal,increased uptake and absorption of SP in Caco-2 cells,and enhanced the intervention effect of SP in type 2 diabetic rats.These results indicated that SMEDDS could increase bioavailability and promote the absorption of SP.