The Extraction, Structural Analysis And Effect Of Hypoglycemic Fraction Screened From Ganoderma Lucidum

Ganoderma lucidum has traditionally been used for the treatment of diabetes in Chinese medicine, however, its anti-diabetic potency and mechanism in vivo is still unclear. Protein tyrosine phosphatase1B (PTP1B), as a typical non-receptor type member of the family of PTPs (protein tyrosine phosphatases, PTP), is a key negative regulator in insulin signaling pathway a novel drugtarget for diabetes and obesity. Discovery for highly effective inhibitors of PTP1B has a promising application in diabetes and obesity therapy.PTP1B inhibitors were screened from the fruiting bodies of G. lucidum by a series of modern extraction technology. As a result, a PTP1B inhibitor was screened from G. lucidum and named FYGL. FYGL has an efficient PTP1B inhibitory potency with IC50value of5.12±0.05μg/mL in a competitive inhibition kinetics mechanism. It was demonstrated that FYGL is a water soluble proteoglycan with protein to polysaccharide ratio of17:77, and a viscosity-average molecular weight of2.6×105. In addition, FYGL can inhibite the activity of α-glucosidase, α-amylase and free radical in vitro while it has low inhibition on T-cell protein tyrosine phosphatase (TC-PTP), which suggests that FYGL has the multiple target point function and good selection on PTPs.Treatment of FYGL for the STZ-induced type2diabetes mice, rats and db/db mice significantly decreased the fasting plasma glucose level, respectively, compared to the diabetic control group. The decrease in the plasma glucose for the FYGL treatment group is comparable with that for metformin and rosiglitazone treatment group. The FYGL does lead to the dose-and time-dependent decrease in the fasting plasma glucose. FYGL could decrease the insulin insistant of T2DM rats and db/db mice and promote the insulin release of T2DM rats. Furthermore, the toxicity of FYGL was preliminarily evaluated as LD50=6g/kg with95%confidence limits of4.8-7.4g/kg. Pharmacology research indicated that FYGL decreased the PTP1B expression and activity in the insulin sensitive tissues of T2DM rats and db/db mice, consequently, increased the tyrosine phosphorylation level of the IR β-subunit in these tissues. At last, FYGL significantly decreased the levels of plasma biochemistry indexes such as free fatty acid, triglyceride, total cholesterol and low density lipoprotein-cholesterol as well as increased the level of high density lipoprotein-cholesterol in T2DM rats. Similar results were found in serum and hepatic lipid profiles in db/db miceIn this work, FYGL decrease the plasma glucose level on the mechanism of inhibiting the PTP1B expression, activity and relative active ratio, consequently, regulating the tyrosine phosphorylation level of the IR β-subunit and the level of hepatic glycogen, thus, resulting in the improvement of insulin sensitivity. As those results, FYGL can also control the biochemistry indexes relative to the type2diabetes with metabolic disorders. Therefore, FYGL is promising as an insulin sensitizer for therapy of diabetes and accompanied dyslipdemia.