Study On The Safety And Mechanism Of Berberine Organic Acid Salt In Reducing Blood Sugar

Berberine hydrochloride?BH?is a plant antibiotic extracted from natural plants for the treatment of intestinal infection.It is inexpensive and relatively safe.In recent years,it has been found to be a new use of old drugs-hypoglycemic.Type 2 diabetes mellitus?T2D?is a series of metabolic disorders such as sugar,protein and electrolyte.T2 D and related complications can cause harm to health and seriously affect the quality of life of patients.The hypoglycemic effect of BH is safe and effective,but it still has the side effects of Hyperchloric acid,low bioavailability and irritation of stomach and stomach,which restricts its clinical application.Based on the above problems,we screened out the organic acids that have health function and harmLess to the human body,and converted to BH,and obtained four kinds of berberine organic acids?BOAs?:Berberine citrate?BC?,berberine?BM?,berberine succinate?BC?,and fumaric berberine?BF?.It also evaluates its safety and bioavailability,and studies the mechanism of its hypoglycemic action by biochemical,pathological,immunohistochemical and molecular biological detection methods.The main results are as follows:1.Security evaluation of BOAs T2 D model was established by feeding high fat and high sugar and intraperitoneal injection of30mg/kg STZ.After 6 weeks of gavage of 500mg/kg and D,the body weight,TC,TG,FBG,FINS and HOMA-IR of BH and BOAs groups were at normal level?p<0.01?.The levels of Na⁺,K⁺,Cl^-,HCO₃^-,pH,PCO₂ and BE in group BH were significantly different from those in normal rats?p<0.05?,but there was no difference in BOAs group.The results showed that BOAs and BH had the same hypoglycemic effect,but BOAs was better in safety.2.Pharmacokinetics and bioavailability evaluation of BOAs in vivo Oral bioavailability is relatively low,which greatly restricts the clinical application of berberine as hypoglycemic agent.Therefore,we study the pharmacokinetics of BOAs in vivo,evaluate its bioavailability,and observe its tissue distribution by living imaging system,and analyze its metabolic behavior in T2 D rats.Each group was gavaged at 0.5,1,1.5,2,3,4,6,8,12 and 24 h after 500mg/kg,and the serum concentration was detected.0.01 mol/LSDS as a sensitizer,in vivo imaging,and finally viscera imaging observation.Compared with the BH group,the Cmax of group BOAs increased significantly?group BF?,AUC_0-?increased significantly?p<0.05?,Cl/F significantly decreased?p<0.05?,and the relative bioavailability of BF,BM,BS and BC were 1.278,1.243,1.3137 and 1.1931 times respectively.BH or BF was mainly distributed in the stomach after oral administration of 1H.After 4h,it was discharged from the small intestine,cecum and rectum.Tissue imaging found that the drugs were accumulated in the liver,kidney and lungs,and were distributed in the intestines,but the stomach and heart did not observe the fluorescence.The results showed that compared with BH,the bioavailability of BOAs increased.3.Study on the hypoglycemic mechanism of BOAs T2 D is closely related to intestinal microorganism and systemic chronic inflammatory reaction.Therefore,we used proteomics and gene sequencing technology to expand the role of BOAs in intestinal flora and TLR4/JNK/PI3 K pathway in T2 D rats.The results showed that The T2 D rats had disorders of glucose and lipid metabolism,an abnormal intestinal microflora,fewer butyrate-producing and probiotic-type bacteria,larger numbers of potentially pathogenic and sulfate-reducing bacteria,and tissue inflammation.Administration of berberine fumarate significantly ameliorated the metabolic disorder,increased the populations of Bacteroidetes,Clostridia,Lactobacillales,Prevotellaceae and Alloprevotella,and reduced those of Bacteriodales,Lacnospiraceae,Rikenellaceae and Desulfovibrio.In addition,it reduced inflammation,inhibiting the overexpression of TLR4,p-JNK,and increasing the expression of PI3 K,GLUT2 and other proteins,thereby promoting the metabolism of glucose.