Antidiabetic with antilipidemic and antioxidant effects of flindersine by enhanced glucose uptake through GLUT4 translocation and PPARγ agonism in type 2 diabetic rats

J Ethnopharmacol. 2022 Mar 1:285:114883. doi: 10.1016/j.jep.2021.114883. Epub 2021 Nov 30.

Abstract

Ethnopharmacological relevance: Medicinal plants have been used by the people of developing countries to treat various diseases. WHO also recommends the use of medicines from plants source. In that, diabetes also one of the diseases that have been treated traditionally by several people all over the world. In India, Toddalia asiatica (L.) Lam. (Rutaceae) is also a medicinal plant used traditionally for the treatment of diabetes in Ayurveda. Moreover, T. asiatica is also used in a polyherbal formulation to treat diabetes.

Aim of the study: This study examined the antidiabetic with antilipidemic and antioxidant effects of flindersine isolated from T. asiatica leaves.

Materials and methods: Diabetes was induced in Wistar rats by feeding a high-fat diet (HFD) for 15 days and injecting a single dose of 40 mg/kg b. wt. of Streptozotocin (STZ). Five days post-injection, the grouped diabetic rats were treated with 20 and 40 mg/kg of flindersine.

Results: Flindersine resulted in a clear decline of blood glucose levels during 28 days of treatment in two different doses. Flindersine also significantly (P ≤ 0.05; P ≤ 0.005) reduced the body weight gain, plasma insulin concentration, urea, creatinine, total cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) levels and significantly increased (P ≤ 0.05; P ≤ 0.005) the total protein level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities compared to the standard drug, pioglitazone. Additionally, flindersine restored the glucose transporter protein 4 (GLUT4), adenosine monophosphate protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) expressions in adipose tissues and skeletal muscles.

Conclusion: It has been found that flindersine has potent antilipidemic and antidiabetic activities by improving insulin sensitivity by enhancing the phosphorylation of AMPK, GLUT4 translocation, and PPARγ agonism on adipose tissue and skeletal muscles of diabetic rats.

Keywords: AMPK; Antidiabetic; Flindersine; GLUT4; PPARγ; Pioglitazone; Streptozotocin.

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Blood Glucose / drug effects
  • Catalase
  • Diabetes Mellitus, Experimental
  • Diabetes Mellitus, Type 2 / chemically induced*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diet, High-Fat / adverse effects
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Glucose / metabolism
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism*
  • Glutathione Peroxidase
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Heterocyclic Compounds, 3-Ring / pharmacology*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Hypolipidemic Agents / chemistry
  • Hypolipidemic Agents / pharmacology
  • Male
  • Molecular Structure
  • PPAR gamma / agonists*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Phytotherapy
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Rats
  • Rats, Wistar
  • Rutaceae / chemistry
  • Superoxide Dismutase

Substances

  • Antioxidants
  • Blood Glucose
  • Glucose Transporter Type 4
  • Heterocyclic Compounds, 3-Ring
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • PPAR gamma
  • Plant Extracts
  • Slc2a4 protein, rat
  • flindersine
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glucose