Globularia alypum Extracts Attenuate Hyperglycemia and Protect against Various Organ Toxicities in Alloxan-Induced Experimental Diabetic Rats

Abstract

In this study, we attempted for the first time to determine the phytochemical compositions and biopharmaceutical properties of Globularia alypum methanol extract (GAME) and Globularia alypum water extract (GAWE). High-performance liquid chromatography with diode array detection (HPLC-DAD) analysis was performed to establish the chemical profile of the investigated extracts. Chemical composition analysis was taken in the presence of various bioactive compounds such as quercetin 7-O-glucoside and apigenin 7-O-glucoside in GAME. In GAWE, various abundant compounds were found in the extract such as quercetin 7-O-glucoside, apigenin, quercetin, apigenin 7-O-glucoside, and cinnamic acid. This study showed that the administration of GAWE and GAME to type 1 diabetic rats decreased fasting blood glucose, protected pancreas β-cells from death and injury, increased liver glycogen rate, and ameliorated oral glucose tolerance test. Moreover, GA reduced weight loss, and diabetes decreased basic physical activity. In addition, the administration of GA extracts in diabetic rats protected from diabetes-induced liver, kidney, testes, heart, and bone toxicities. Conclusion. GAWE has possible value for antidiabetic oral medication.

Figure 1

HPLC chromatogram of water (a) and methanol (b) extracts from leaves of GA.

Figure 2

Effect of GAWE and GAME on blood glucose level, liver and muscle glycogen levels, and OGGT. The administration of GAWE or GAME to diabetic rats decreases serum glucose rate, increases the muscle and liver glycogen levels, and ameliorates the insulin sensitivity. The values are statistically presented as follows: ^@p < 0.05 as compared to normal rats; ^#p < 0.05 as compared to alloxan-induced type 1 diabetes; ^&p < 0.05 as compared to GAWE diabetic treated rats.

Figure 3

Effect of GAWE and GAME on alloxan-induced β-cells death staining by H&E (100 (X). C: normal β-cells; D: alloxan-induced severe β-cells death; (D + GAWE and D + GAME): a protective effect was shown in the pancreas of diabetic rats treated with GAWE or GAME. The protective effect was more pronounced in GAWE diabetic treated rats.

Figure 4

Effect of GAWE and GAME supplements on diabetes-induced liver injury. C: normal liver tissues and architecture. D: the liver of alloxan-induced type 1 diabetes-hyperglycemia-induced apparition lymphocytic infiltrate in the portal and sinusoidal spaces. D + GAWE and D + GAME: diabetic rats treated with GAWE or GAME; prevention of liver-infiltrating lymphocytes (H&E 100X).

Figure 5

C: normal rat kidney. D: diabetes-provoked inflammation in kidney tissues. D + GAWE and D + GAME: administration of GAWE or GAME to alloxan-induced type 1 diabetes reverted and inhibited inflammation in kidney tissues (H&E 100X).

Figure 6

Effect of type 1 diabetes on the histological morphology of rat testes (400 (X). C: control rats showing a regular development of spermatogenesis. D: diabetic rats showing decrease in sperm count in somniferous tubules. In GAME- and GAWE-treated rats, spermatogenesis proceeded normally and somniferous tubules sperm count was near to that of normal rat germ cells.

Figure 7

Effect of GAWE or GAME on type 1 diabetes cardiac injury in rats. (C) Control groups: normal cardiac architecture. D: alloxan-treated group showing anarchized myocardial fibers. D+GAWE and D+GAME: diabetic group received GAWE or GAME (200 mg/kg) showing prevention and amelioration of anarchized myocardial fibers.

Figure 8

C: bone and normocellular bone marrow. D: in diabetic rats, we showed a spongy bone is composed of a network of trabeculae separated by interconnecting spaces. In diabetic rats treated with GAME or GAWE, the bone tissues were similar to that of the control group.