"Ficus johannis Boiss. leaves ethanolic extract ameliorate streptozotocin-induced diabetes in rats by upregulating the expressions of GCK, GLUT4, and IGF and downregulating G6P"

Environ Sci Pollut Res Int. 2023 Apr;30(17):49108-49124. doi: 10.1007/s11356-023-25765-4. Epub 2023 Feb 11.

Abstract

The leaves of Ficus johannis Boiss (F. johannis), commonly known as Fig tree, Anjir, and Teen, are used by the folk medicinal practitioners in Iran for controlling hyperglycemia in diabetic patients. This study investigated the pharmacological basis for antidiabetic effect of the ethanolic extract of F. johannis leaves using in vitro and in vivo experimental models. Qualitative screening of phytochemicals, estimation of total phenolic and flavonoid contents, and in vitro antioxidant and α-amylase inhibition assays were performed. Moreover, the High-performance liquid chromatography (HPLC) quantification, acute toxicity, glucose tolerance, and in vivo antidiabetic effect along with the evaluation of gene expressions involved in diabetes mellitus were carried out. Significant quantities of phenolic (71.208 ± 2.89 mgg-1 GAE) and flavonoid (26.38 ± 3.53 mgg-1 QE) were present. Inhibitory concentration (IC50) of the plant extract exhibited an excellent in vitro antioxidant (IC50 = 33.81 µg/mL) and α-amylase (IC50 = 12.18 µg/mL) inhibitory potential. The HPLC analysis confirmed the gallic acid (257.79 mgg-1) as main constituent of the extract followed by kaempferol (22.86 mgg-1), myricetin (0.16 mgg-1), and quercetin (3.22 mgg-1). Ethanolic extract displayed glucose tolerance in normo-glycemic rats. Streptozotocin-induced hyperglycemia declined dose dependently in the extract treated rats with improvement in lipid profile and liver and renal function biomarkers. The F. johannis-treated groups showed an increase in mRNA expressions of glucose transporter 4 (GLUT-4), glucokinase, insulin growth like factor 1 and peroxisomal proliferator activating receptor gamma in pancreas. However, the Glucose-6-phosphatase was downregulated. Present study suggests that the ethanolic extract of F. johannis leaves demonstrates a good anti-diabetic profile by improving insulin sensitivity, GLUT-4 translocation, and carbohydrate metabolism while inhibiting lipogenesis.

Keywords: Antioxidant; Diabetes mellitus; Ficus johannis; Polymerase chain reaction; Streptozotocin.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental* / chemically induced
  • Diabetes Mellitus, Experimental* / drug therapy
  • Ethanol
  • Ficus* / chemistry
  • Ficus* / metabolism
  • Flavonoids / pharmacology
  • Germinal Center Kinases / drug effects
  • Glucose
  • Glucose Transporter Type 4 / drug effects
  • Glucose-6-Phosphatase / drug effects
  • Hyperglycemia* / drug therapy
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin-Like Growth Factor I / drug effects
  • Phenols
  • Plant Extracts* / chemistry
  • Plant Extracts* / therapeutic use
  • Rats
  • Streptozocin
  • alpha-Amylases

Substances

  • alpha-Amylases
  • Antioxidants
  • Blood Glucose
  • Ethanol
  • Flavonoids
  • Glucose
  • Hypoglycemic Agents
  • Phenols
  • Plant Extracts
  • Streptozocin
  • Germinal Center Kinases
  • Glucose Transporter Type 4
  • Insulin-Like Growth Factor I
  • Glucose-6-Phosphatase