Background
World Health Organization (WHO) demonstrated that 422 million people have diabetes in 2014. The global prevalence of diabetes among adults (>18) is 8.5%. WHO projects that diabetes mellitus will be 7th leading cause of death in 2030. Certain studies have demonstrated that the Thymus species, members of Lamiaceae, have antiinflammatory, antifungal, antiviral, antioxidant, anticancer and antidiabetic effects (1). Thymus praecox subsp. skorpilii var. skorpilii is a traditional herbal medicine has attracted considerable interest to treat type II diabetes mellitus (T2DM) in Merzifon region of Turkey.  There has not been any study that evaluates the antidiabetic effect of Thymus praecox.
Aim
This study was designed to investigate the antidiabetic effects and the mechanism of action of Thymus praecox subsp. skorpilii var. skorpilii methanol extract. The aim of this study is to support the medicinal treatment of T2DM and to reduce dose or to prevent possible side effect of likely used oral antidiabetics by the usage of extracts.
Method
Sprague Dawley rats were divided into four groups as control (distilled water, 10 ml/kg/day, i.g.), diabetes,Thymus praecox methanolic extract (100 mg/kg/day, i.g.) and Metformin (400 mg/kg/day, i.g.) (n=6). To identify effective dose of Thymus praecox extract, oral glucose tolerance test (OGTT) was performed in healthy rats. A single intraperitoneal injection of nicotinamide (100 mg/kg), followed after 15 min by STZ (55 mg/kg) were given to induce type-2 diabetes in rats (2). Afterwards, insulin tolerance test (ITT), OGTT, blood glucose levels (BGL) and animal weights were used for evaluating the antidiabetic effects. ITT and OGTT was performed for all groups after an overnight fast on day 15 and 18, respectively. On day 21, the rats were decapitated. To investigate the exact mechanism of action, several tissues such as liver, skeletal muscle, small intestine, kidney, pancreas and also serum were collected to measure the level of aspartate aminotransferase, alanine aminotransaminase (ALT), creatinin, insulin etc. by ELISA. Two-way ANOVA with Bonferroni post test was performed using GraphPad Prism version 6.00 for Mac OS X, GraphPad Software.
Results
According to the results of OGTT in healthy rats, the most effective dose was chosen as 100 mg/kg body weight for Thymus praecox extract. After first week, BGL of non-treated diabetic rats showed a significant augmentation (p<0.0001) compared to control group. Conversely, Thymus praecox extract caused a considerable fall by 47% (p<0.0001) in BGL compared with diabetic rats and it lasted for three weeks. At the end of the study, the lowest average BGL in treatment groups belongs to metformin (132.50±7.40 mg/dL), which was only 10% lower than Thymus praecox extract group. In OGTT, BGL enhanced in time and was sustained until 2 hours in diabetic rats. Unsurprisingly, metformin significantly (p<0.01) dropped BGL beginning from 30 min compared to Thymus praecox extract group. However, Thymus praecox extract exhibited an important blood glucose reduction (67%, p<0.01) compared to diabetes group and reached to that of metformin at the second hour. In ITT, BGL of diabetes group sharply decreased (p<0.001) at the end of 90 min compared to beginning. On the contrary, control and treatment groups protected their BGL during 90 min. Furthermore, Thymus praecox extract treatment decreased creatinin, alanine aminotransaminase (ALT); conversely, increased insulin level compared to diabetic rats.
Discussion
Our results showed that Thymus praecox extract not only increased glucose utilization by peripheral tissues and enhanced glycogen depots in the liver due to the repairment of postponed insulin response but also decreased ALT and creatinin levels that demonstrate impairment of the functions of liver and kidney compared to diabetic rats. Consequently, Thymus praecox extract and metformin ameliorated impaired glucose tolerance via rising plasma insulin levels. As a result, Thymus praecox extract attenuated insulin resistance and exerted potent insulin-sensitizing properties. 
1.	Iauk L, Acquaviva R, Mastrojeni S, Amodeo A, Pugliese M, Ragusa M, et al. Antibacterial, antioxidant and hypoglycemic effects of Thymus capitatus (L.) Hoffmanns. et Link leaves' fractions. Journal of enzyme inhibition and medicinal chemistry. 2015;30(3):360-5.
2.	Adam SH, Giribabu N, Rao PV, Sayem AS, Arya A, Panichayupakaranant P, et al. Rhinacanthin C ameliorates hyperglycemia, hyperlipidemia and pancreatic destruction in streptozotocin-nicotinamide induced adult male diabetic rats. European journal of pharmacology. 2016;771:173-90.

Antidiabetic effects of Thymus praecox on streptozotocin/nicotinamide-induced rat model of type II diabetes