Search

Thymus praceox and Salvia triloba possess anti-inflammatory and anti-diabetic effects on type 2 diabetic ratsBackground: Thymus praceox subsp. skorpilii var. skorpilii is a species of Thymus, from Lamiaceae and have proven antioxidant effect. T.vulgaris and T.cramanicus, other thymus species, have shown antidiabetic effects in previous studies (1).In addition, previous studies have reported that salvia species have antioxidant, anti-inflammatory and hypoglycemic effects. Salvia triloba is a subspecies of Lamiaceae and there is no study have demonstrated its antidiabetic effect. The pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance are associated with inflammation as a result of immun system activation. Additionally, oxidative stress has influence cytokine mediated inflammation. Adipose tissue has been shown to act as an endocrine gland through the release of adipokines such as adiponectin, leptin and adipsin; implicated in physiological functions such as insulin sensitivity, appetite modulation and inflammatory response. Moreover, some studies suggested that adipokines may be the target molecules for treatment of T2DM. Adipose tissue caused to elevation of insulin resistance due to the indication of cytokine production which leads to inflammation in diabetic individuals (2).Aim: This study was designed to investigate the effects of Thymus praceox and Salvia triloba on adiponectin and inflammation which play roles for pathogenesis of T2DM. Furthermore, to evaluate the severity of anti-inflammatory effect, new researches will be designed regarding this study.Method: Sprague Dawley rats (200-300 g) were injected streptozotocin (STZ)/nicotinamide(NA) intraperitoneally (i.p.) to induce T2DM model. After 72 hours injection, blood glucose levels were measured and more than 200 mg/dl were determined as diabetic. Blood samples were collected weekly to determine postprandial blood glucose levels. Before starting diabetes study effective doses of Thymus praceox subsp. skorpilii var. skorpilii methanolic extract (100 mg/kg) and Salvia triloba methanolic extract (200 mg/kg) acquired from oral glucose tolerance test in normal rats. Treatments started after three days of diabetes induction and administered daily. Rats are divided into 5 groups; diabetes group, 1th therapy group, 2nd therapy group , positive control group (therapy with metformin) and control group. On day 21, all rats were decapitated and blood samples were taken for evaluating tumor necrosis factor alpha (TNF-u03b1), interleukin-6 (IL-6), interleukin-1u03b2 (IL-1u03b2), interleukin-10 (IL-10) and adiponectin levels by ELISA.Results: TNF-u03b1, IL-6 and IL-1u03b2 are pro-inflammatory cytokines and their levels increased in diabetes group compared to control group while these levels decreased in therapy groups and positive control group in this study. Controversially, adiponectin and the anti-inflammatory cytokine IL-10 levels decreased in diabetes group compared to control group while Salvia triloba extract and Thymus praceox extract prevented the decreases of IL-10 and adiponectin. At the end of experiment, it was demonstrated that both Thymus praceox extract and Salvia triloba extract performed a significant fall in blood glucose level with 58% and 45%, (p

Abstract Title: The inhibitory effects of Salvia triloba and Thymus praecox on acetylcholinesterase activity in diabetic ratsBackgroundDiabetes mellitus (DM) is a metabolic disease characterized by long-term complications including cerebrovascular injury and cognitive disorders. Acetylcholinesterase (AChE) which is involved in numerous pathways in the central nervous system regulates the level of acetylcholine (ACh) which plays vital functions such as memory, learning, modulation of cerebral blood flow, movement control, neurotransmission as well (1). Recent studies have shown that hypoinsulinemia and insulin resistance is the reason of the decreased level of ACh and contribute the possible biochemical link between DM and cognitive disorders including Alzheimeru2019s disease. Studies with plants have shed light on the correction of cognitive functions of diabetes mellitus with increased AChE activity. Some Salvia and Thymus species of the Lamiaceae family have antidiabetic effects (2). There is no study on antidiabetic activity of Salvia triloba and Thymus praecox.AimTo investigate the effects of Salvia triloba and Thymus praecox on brain acetylcholinesterase activities in diabetes mellitus. With the help of obtained results, further studies will be carried out for ameliorating cognitive dysfunction effectively and also supporting current treatments.MethodThe rats were divided into five groups (6 rats per group): Group-I: Normal control, Group-II: Diabetic control, Group-III: Treatment with Salvia triloba methanolic extract, (200 mg/kg/day, i.g.), Group-IV: Treatment with Thymus praecox methanolic extract, (100mg/kg/day, i.g.), Group-V: Treatment with Metformin (400 mg/kg/day, i.g.). Type 2 DM was induced experimentally in these groups of rats by the intraperitoneal administration of 55 mg/kg of STZ and 100 mg/kg nicotinamide, except control group. Treatments were carried out after induction of DM and lasted for 3 weeks except decapitation day. The AChE enzymatic assay was determined according to the method of Ellman et al. The reaction mixture (2 mL final volume) contained 100 mM K+-phosphate buffer, pH 7.5 and 1 mM 5,50-dithiobisnitrobenzoic acid (DTNB). The method is based on the formation of the yellow anion, 5, 50- dithio-bis-acid-nitrobenzoic, measured by absorbance at 412 nm during 2 min incubation at 25u00b0C. The enzyme (40u201350 mg of protein) was pre-incubated for 2 min. The reaction was initiated by adding 0.8 mM acetylthiocholine iodide (AcSCh). All samples were in triplicate readings and the enzyme activities were expressed in mmol AcSCh/h/mg of protein.ResultsThymus praecox and Salvia triloba in methanolic extract considerably decreased (pu02c20.0001) blood glucose levels compared to diabetic rats and performed this drop for 3 weeks. Thymus praecox extract reached its maximum hypoglycemic effect (141.83u00b17.31, pu02c20.0001) in 2 weeks. At the same time, Thymus praecox and Salvia triloba extract also showed strong hypoglycemic effect (164.83u00b113.30, pu02c20.0001). The diabetic group exhibited a significant increase (pu02c20.001) in AChE activity in prefrontal cortex compared to the control and the treatment groups. However Salvia triloba extract and Thymus praecox extract reverted this increase (pu02c20.001) in AChE activity induced by diabetes after 3 weeks of treatment. The metformin group decreased (%47, pu02c20.001) in AChE activity compared to diabetic groups. Salvia triloba extract (%37, pu02c20.001) and Thymus praecox extract group (%41, pu02c20.001) a considerably decrease in AChE activity compared to diabetic group. The metformin group did not show a significant difference in enzyme activity compared to the control group. However, Salvia triloba and Thymus praecox increased (pu02c20.05) in AChE activity compared to control groups.DiscussionOur study results showed that an increase in AChE activity in type 2 diabetic rat brains. This increase in AChE activity in the T2DM rat model can be linked to depletion in cholinergic actions leading to defective neurotransmission and cognitive dysfunction as a result of decreased levels of ACh in the synaptic cleft. We showed that the reestablishment of AChE activity by Salvia triloba extract and Thymus praecox extract which for the first time demonstrated antidiabetic activities can contribute to the maintenance of cholinergic signaling in diabetic rats. In the light of the results, these plants give a valuable direction for researchers on the future for diabetes-related cognitive disorders. 1. Jacobson AM., et al., Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group, Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007;356(18):1842u20131852.2. Davids D., et al., Ethnobotanical survey of medicinal plants used to manage High Blood Pressure and Type 2 Diabetes Mellitus in Bitterfontein, Western Cape Province, South Africa, J Ethnopharmacol. 2016 Dec 24;194:755-766.