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Background Insulin resistance is a hallmark of type 2 diabetes mellitus (T2DM) and the underlying cause of various metabolic changes observed in type 2 diabetic patients. This study investigated the molecular basis of the anti-hyperglycemic activity of the lanosteryl triterpene (RA-3), from Protorhus longifolia stem bark, in hyperlipidemic and streptozotocin (STZ)-induced T2DM in rats. Methods The high-fat diet fed (HFD) and STZ-induced T2DM in rat model was used to evaluate the anti-hyperglycemic activity of RA-3. The hyperlipidemic rats received a single intraperitoneal injection of STZ (35 mg/kg body weight) to induce T2DM. The experimental animals received a daily oral single dose of RA-3 (100 mg/kg body) for a period of 28 days, whiles the control group received distilled water only. The animals were euthanized, and skeletal muscle was collected for protein (IRS-1, AKT, GSK and GLUT 4) expression analysis. Western blot confirmed expression of the proteins. Results Treatment of the diabetic animals with the RA-3 showed marked reduction in fasting plasma glucose levels in comparison to the untreated diabetic group animals. A significant decrease in p-GSK-3β and p-AKT expression was observed, whereas the expression of IRS-1 ser307 were increased when compared to the diabetic control group. This effect was ablated upon treatment with RA-3 and this was concomitant to an observed increase in GLUT 4 expression. Conclusions The results obtained in the present study strongly suggested that the anti-hyperglycemic effect of RA-3 could partly be associated with its ability to improve cellular glucose uptake in muscle tissue from T2DM.

BackgroundA substantial literature supports antidiabetic properties of the lanosteryl triterpene (methyl-3β-hydroxylanosta-9,24-dien-21-oate, RA-3) isolated from Protorhus longifolia stem bark. However, the molecular mechanism(s) associated with the antihyperglycemic properties of the triterpene remained to be explored. The current study aimed at investigating the molecular mechanism(s) through which RA-3 improves insulin signaling in streptozotocin-induced type 1 diabetic rats.MethodsThe type 1 diabetic rats were treated daily with a single oral dose of RA-3 (100 mg/kg) for 28 days. The rats were then sacrificed, and blood, skeletal muscle and pancreases were collected for biochemical, protein expression and histological analysis, respectively.ResultsPersistently high blood glucose levels in the diabetic control rats significantly increased expression of IRS-1Ser307 while the expression of p-Akt Ser473, p-GSK-3β Ser9, GLUT 4 and GLUT 2 were decreased. However, enhanced muscle insulin sensitivity, which was indicated by a decrease in the expression of IRS-1ser307 with a concomitant increase in the p-AktSer473, p-GSK-3β Ser9, GLUT 4 and GLUT 2 expression were observed in the diabetic rats treated with RA-3. The triterpene-treated animals also showed an improved pancreatic β-cells morphology, along with increased C-peptide levels. An increase in the levels of serum antioxidants such as catalase, superoxide dismutase, and reduced glutathione was noted in the rats treated with the triterpene, while their serum levels of interleukin-6 and malondialdehyde were reduced.ConclusionsIt is apparent that RA-3 is able to improve the insulin signaling in type 1 diabetic rats. Its beta (β)-cells protecting mechanism could be attributed to its ability to alleviate inflammation and oxidative stress in the cells.

In the study, ultraperformance liquid chromatography–quadrupole time-of-flight–mass spectrometry analysis of Leucosidea sericea leaf and stem extracts led to the identification of various classes of compounds. Further chromatographic purifications resulted in the isolation of 22 compounds that consisted of a new triterpenoid named leucosidic acid A ( 1 ), an acetophenone derivative 2 , a phloroglucinol derivative 3 , three chromones 4–6 , seven pentacyclic triterpenoids 7–13 , a phytosterol glucoside 14 , a flavonoid 15 , and seven flavonoid glycosides 16–22 . Nineteen of these compounds including the previously undescribed triterpenoid 1 are isolated for the first time from L. sericea . The structures of the isolated compounds were assigned based on their high-resolution mass spectrometry and nuclear magnetic resonance data. Some of the isolated triterpenoids were evaluated for inhibitory activity against α-amylase, α-glucosidase, and pancreatic lipase. Of the tested compounds, 1-hydroxy-2-oxopomolic acid ( 7 ) and pomolic acid ( 13 ) showed higher potency on α-glucosidase than acarbose, which is used as a positive control in this study. The two compounds inhibited α-glucosidase with IC 50 values of 192.1 ± 13.81 and 85.5 ± 6.87 μM, respectively.

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