| Entada phaseoloides （Linn.） Merr. belongs to Entada of Leguminosae plants,which widely distributes in America and Africa, about30species exist all around theworld. Only one species exists in China. Their seeds have been long used as a folkmedicine by Dai people, one of the ethnic minorities in China, for the treatment ofstomachache, haemorrhoids, edema, and constipation. In addition, antibacterial,antioxidant, hypoglycemic, antitumor, antiinflammation and analgesia effect and otherbiological activity had been reported by researchers through Modern pharmacologicalresearch methods. The aim of the study is to evaluate the potential mechanism ofantidiabetic effect of total saponins from Entada phaseoloides （Linn.） Merr.（TSEP） intype2Diabetes mellitus （T2DM） rats, in order to better develop and utilize thismedicinal plant resources, and create more economic benefits for the society.T2DM rats were induced by high-fat diet and low-dose streptozotocin （STZ）.Forty-eight rats were randomly divided into six equal groups as follows: normalcontrol rats, T2DM rats treated with vehicle alone,200mg.kg-1of metformin,25,50and100mg.kg-1of TSEP. The body weights of rats were monitored daily during theexperimental period and the treatment was given orally using an intragastric tube oncea day.Our present study demonstrates hypoglycemic activities of various dosage ofTSEP in T2DM rats, and this effect was dose-dependently rescued by TSEP treatment.After treating these rats with TSEP at100mg.kg-1for21days, the value of plasmaglucose was9.8mmol.L-1, lower than10.1mmol.L-1of the metformin group, and thecorresponding period the plasma glucose level of T2DM rats was18.3mmol.L-1. Ininsulin tolerance test （ITT） and oral glucose tolerance test （OGTT）, the improvingeffects on insulin resistance （IR） and blood glucose regulation of TSEP to varyingdegrees were observed. In T2DM rats, dramatically increase in serum insulin levelwas observed, and after treatments with both TSEP and metformin, both of them weredecreased compared to vehicle treatment. Metabolic disorders such as dyslipidemiaand tissue steatosis have been observed in our experimental T2DM rat model, treating these rats with TSEP effectively decreased the levels of serum total cholesterol （TC）,triglyceride （TG）, free fatty acid （FFA） and low density lipoprotein cholesterol（LDL-C）, also increased the level of serum high density lipoprotein cholesterol（HDL-C）. Furthermore, both tissue steatosis and adipose degeneration were observedin the liver tissues of the T2DM rats, as shown in histological sections of rat livers,and those characteristics are obviously different from their normal counterparts.In T2DM rats, very significant increases of TC and TG levels in the liver andskeletal muscle tissues were observed in this experiment, which is decreased aftertreating these rats with TSEP and metformin. For100mg.kg-1TSEP and metformin,best therapeutic effect were obtained, which close to the normal control rats.Meanwhile, very significant decrease of phosphorylated AMP-activated protein kinase（P-AMPK） level in liver and skeletal muscle tissues were observed by using WesternBlot method, but the expression level of AMP-activated protein kinase （AMPK）showed no significant differences with the others. Treating them with metformin andTSEP resulted in increase of P-AMPK level compared to vehicle treatment. Thisobservation implied that the mechanisms of antidiabetic effect of TSEP exerted itsthrough improving the level of P-AMPK.To explore the possible mechanism underlying the antidiabetic activity of TSEP,we evaluate the potential improve effect of TSEP on oxidative stress and low-gradeinflammation of the rats. The oxidative stress and low-grade inflammation status areassociated with the development of T2DM. In this study, both increased level ofmalondialdehyde （MDA） and decreased levels of superoxide dismutase （SOD） andglutathione （GSH） in rats serum demonstrated that rats were in ststus of oxidativestress. Additionally, increased level of interleukin-6（IL-6）, tumor necrosis factor-alpha （TNF-α） and C-reactive protein （CRP） reflected that rat were in low-gradeinflammatory status. Treating them with metformin and TSEP resulted in decrease ofthose indicator level compared to vehicle treatment. In this study, analysis ofhistopathological examination of pancreatic tissue demonstrated that TSEP efficientlyprotected pancreatic tissue, and alleviated damage and apoptosis of pancreatic betacell. All of those observation implied that the mechanisms of antidiabetic effect ofTSEP exerted its through what is said above. |
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