Bioactivity-guided isolation of the antidiabetic principle in Pterocarpus Santalinoides leaf extract

Abstract Pterocarpus santalinoides is used in Nigerian ethnomedicine to treat diabetes mellitus. This study aimed to establish the antidiabetic property of the plant, and isolate and characterize its active principle. Dried and pulverized leaves (500 g) of P. santalinoides were extracted with 1.8 L of 80 % hydromethanol by cold maceration. The dried extract (10 g) was partitioned into n-hexane, ethyl acetate (EtOAc), n-butanol, and water. Antidiabetic activitiy-guided isolation by column chromatographic separation of the EtOAc soluble and purification of the sub-fractions by repeated preparative thin layer chromatography (pTLC) yielded a C-glycosyl flavonoid, identified as isovitexin. The chemical structure was elucidated based on high-resolution mass spectroscopy, 1D, and 2D nuclear magnetic resonance spectroscopic analyses. Alloxan-induced diabetic rat model was adopted for antidiabetic screening. The extract of P. santalinoides (100-200 mg/kg), fraction F4 (50 mg/kg), sub-fraction F4.3 (10 mg/kg), and the semi-purified compound F4.3.2 (5 mg/kg) significantly (p<0.05) reduced the fasting blood glucose of alloxan-induced diabetic rats, causing 48.4, 69.4, 57.7 and 64.5 % antidiabetic activity respectively, compared with > 68 % recorded in glibenclamide (2 mg/kg) control. These results reveal that isovitexin is the antidiabetic principle in P. santalinoides

Antidiabetic, antilipidemic, and antioxidant activities of Gouania longipetala methanol leaf extract in alloxan-induced diabetic rats.

CONTEXT: Gouania longipetala Hemsl. (Rhamnaceae) is used in folkloric medicine for treating diabetes mellitus and its associated symptoms. OBJECTIVE: This study evaluated the antidiabetic antilipidemic and antioxidant activities of the plant methanol leaf extract. MATERIALS AND METHODS: Diabetes was induced in rats by intraperitoneal injection of alloxan monohydrate (160 mg/kg). Three test doses (50, 100, and 150 mg/kg) of G. longipetala extract (GLE) were administered orally and the effects were compared with glibenclamide (2 mg/kg). The effect of GLE on hyperglycemia and sub-acute study for 21 d were carried out using its effect on fasting blood sugar (FBS) level. Serum biochemistry and antioxidant activity were evaluated. Histopathological evaluation of the pancreas was also done. RESULTS: The LD50 of G. longipetala was found to be >4000 mg/kg. The extract significantly (p < 0.0001) decreased the FBS levels of treated rats from 16.2 ± 2.03 to 6.5 ± 1.52 mM/L at 150 mg/kg within 24 h. The extract decreased FBS levels of rats by 62.0, 74.8, and 75.0% on day 21 at 50, 100, and 150 mg/kg, respectively. GLE reduced the level of malondiadehyde from 23.0 ± 1.34 to 10.3 ± 0.43 mg/dL, increased superoxide dismutase activities from 2.97 ± 0.34 to 5.80 ± 0.53 IU/L at 150 mg/kg, and improved the serum lipid profile of treated rats. GLE also caused restoration of the altered histopathological changes of the pancreas. DISCUSSION AND CONCLUSION: Gouania longipetala demonstrated significant antidiabetic, antilipidemic, and antioxidant activities that may be due to its multiple effects involving both pancreatic and extra-pancreatic mechanisms.

Antihyperglycemic effects of the methanol leaf extract of Diaphananthe bidens in normoglycemic and streptozotocin-induced hyperglycemic rats

OBJECTIVE@#To evaluate the methanol leaf extract of Diaphanathe bidens (D. bidens) (AFZEL. EX SW) SCHLTR for antihyperglycemic activity in order to confirm it antidiabetic potential.@*METHODS@#D. bidens was extracted by cold maceration for 48 h and concentrated in vacuo to yield D. bidens extract (DBE). Hyperglycemia was induced by intraperitoneal administration of streptozotocin (75 mg/kg). Oral glucose tolerance test was done with 2 g/kg glucose load in normal rats. DBE (150, 300 and 600 mg/kg) was administered orally, while tolbutamide (100 mg/kg, p.o.) was used as the standard reference drug. Blood glucose levels determined using ACCUCHEK glucose auto-analyzer. The acute toxicity and phytochemical studies were also carried out.@*RESULTS@#DBE (600 mg/kg) and tolbutamide (100 mg/kg) significantly (P<0.05, 0.005) reduced blood glucose levels of rats between 120 and 480 min post administration in normal rats. In the streptozotocin- induced hyperglycemic rats, DBE (150, 300, 600 mg/kg) caused significant (P<0.001) dose- and time- dependent reduction in the blood glucose levels by 1.7%, 22.8% and 43.4%, respectively at 480 min compared to the negative control group. DBE (600 mg/kg) reduced the blood glucose level of rats by 1.2% in the oral glucose tolerance test when compared with the normal saline treated group. The acute toxicity test showed that DBE was safe at the doses used and the phytochemical screening revealed the presence of saponins, steroids, tannins and terpernoids.@*CONCLUSIONS@#D. bidens extract possess antihyperglycemic activity which may be mediated through pancreatic and extra-pancreatic pathways, thereby justifying it folkloric use.

Glucose uptake-enhancing activity of the ethyl acetate extract of Dennettia tripetala in 3T3-L1 adipocytes.

Glucose uptake-enhancing activity of the ethyl acetate extract of Dennettia tripetala (EDT) was investigated using 3T3-L1 adipocytes. EDT yielded 4.43 percent w/w dry matter, showed the presence of alkaloids and flavonoids, contained calcium, iron, zinc, magnesium, copper and manganese. Out of the five extracts of D. tripetala, EDT gave the highest activity (75 percent) in enhancing glucose uptake in 3T3-L1 adipocytes, which was not significantly (p > 0.05) different from insulin (340 nM), the standard drug. EDT caused concentration-dependent increase in glucose uptake with maximal effect at 5 µg/ml, but further increase beyond 10 µg/ml caused a shut down in glucose uptake. Optimal effect was achieved at 16 h post incubation. There was no synergistic effect with increasing doses (2.5, 5.0, 10 µg/ml) of sub maximal concentrations of insulin, rather there was significant (p < 0.05) decrease compared with insulin (340 nM) alone. Unlike other protein inhibitors used, brefeldin significantly (p < 0.05) inhibited EDT-induced glucose uptake by more than 40 percent. In conclusion, EDT enhanced glucose uptake partly by the mobilization of glucose uptake proteins from the interior of the cell to plasma membrane via the Golgi apparatus. Therefore, this mechanism may be responsible for the antihyperglycaemic effect of EDT reported in our previous study.