The methanolic extract of Thymus praecox subsp. skorpilii var. skorpilii restores glucose homeostasis, ameliorates insulin resistance and improves pancreatic β-cell function on streptozotocin/nicotinamide-induced type 2 diabetic rats

J Ethnopharmacol. 2019 Mar 1;231:29-38. doi: 10.1016/j.jep.2018.10.028. Epub 2018 Nov 3.

Abstract

Ethnopharmacological relevance: Thymus praecox subsp. skorpilii var. skorpilii (syn. Thymus praecox subsp. jankae (Celak.) Jalas) is consumed as a Turkish folk medicine for the treatment of spasm, sore throat and shortness of breath, also having strong antioxidant activity and the leaves of the plant have been utilized for the treatment of diabetes as the decoction in Turkey.

Aim of the study: In the present study, we aimed to investigate the potential mechanism of antidiabetic action of Thymus praecox subsp. skorpilii var. skorpilii methanolic extract (TPSE) on streptozotocin (STZ)/nicotinamide (NA)-induced type 2 diabetic rats.

Materials and methods: Sprague Dawley rats were randomly divided into four groups; control, diabetes, TPSE (100 mg/kg b.w, p.o.) and metformin group (400 mg/kg b.w, p.o.). Diabetes was established in all groups except control group by 55 mg/kg STZ (i.p.) for once 15 min after 100 mg/kg NA injection. 3 days after STZ/NA injection, treatments were administered for three weeks and then rats were decapitated; tissue and blood samples were obtained for measuring the level of glucose transporters (both GLUTs and sodium glucose co-transporters (SGLTs)), enzymes related to glucose (Hexokinase (HK), phosphoenolpyruvate carboxykinase (PEPCK), α-glucosidase) and lipid metabolism (Acetyl-coenzyme carboxylase (ACC)), AST, ALT, creatinine, insulin, anti-inflammatory (IL-10) and inflammatory (TNF-α, IL-1β, IL-6) cytokines, AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPAR-γ) and glucagon like peptide-1 (GLP-1). Histopathological alterations of the pancreas were examined.

Results: After three weeks of treatment, TPSE has exhibited a significant reduction of plasma levels of the proinflammatory cytokines. Besides, TPSE treatment elevated plasma insulin levels and normalized blood glucose levels. Moreover, it improved the values of AMPK in liver and GLP-1 in pancreas. Increased α-glucosidase, PEPCK, GLUT-2 and SGLTs levels with the induction of diabetes considerably lowered with TPSE treatment. Especially on SGLT-2, TPSE achieved a more prominent decrease. After the atrophy in Langerhans islets due to diabetes induction, treatment was found to prevent the damage of islets.

Conclusions: Based on the findings presented here, it has been concluded that TPSE has marked antidiabetic effects through various pathways on STZ/NA-induced diabetic rats and it may potentially be used as an effective treatment for type 2 diabetes mellitus (T2DM). Further research on isolation of the bioactive components is underway.

Keywords: AMPK; Diabetes; GLUTs; Inflammation; Medicinal plants; Metabolism; SGLTs; STZ/NA; Thymus praecox.

MeSH terms

  • Animals
  • Cytokines / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glucose / metabolism
  • Homeostasis / drug effects
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance
  • Insulin-Secreting Cells / drug effects
  • Methanol / chemistry
  • Phytotherapy
  • Plant Components, Aerial / chemistry
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use*
  • Rats, Sprague-Dawley
  • Solvents / chemistry
  • Thymus Plant*

Substances

  • Cytokines
  • Hypoglycemic Agents
  • Plant Extracts
  • Solvents
  • Glucose
  • Methanol