Antidiabetic potential of gallic acid from Emblica officinalis: Improved glucose transporters and insulin sensitivity through PPAR-γ and Akt signaling

Phytomedicine. 2020 Jul 15:73:152906. doi: 10.1016/j.phymed.2019.152906. Epub 2019 Apr 1.

Abstract

Background: Nature has gifted a variety of vital phytochemicals having potential therapeutic application against various ailments. Emblica officinalis (E. officinalis), an ancient plant, has long been used as a remedy for diabetes and cardiovascular complications, and presence of abundant amount of gallic acid could be accountable for its medicinal potential.

Purpose: The study was aimed to determine the in-vivo and in-vitro anti-diabetic potential of gallic acid and fruit juice of E. officinalis. Molecular mechanism of gallic acid as well as fruit juice of E. officinalis for anti-diabetic potential has also been revealed.

Experimental study design: Anti-diabetic potential of E. officinalis and gallic acid was evaluated in 3T3-L1 preadipocytes and various animal models like db/db mice and fructose administered rats. PPAR-γ expression and glucose translocation were observed using western blot and PCR techniques.

Results: Treatment of E. officinalis fruit juice and gallic acid facilitated their glucose homeostasis; improved insulin sensitivity; reduced obesity; abridged elevated blood pressure and declined cholesterol level, and also induced adipogenesis in 3T3-L1 adipocytes. Mechanistically, treatment increased expression of PPAR-γ through activation of C/EBPs and simultaneously increased Glut4 translocation in 3T3-L1 adipocytes. Moreover, gallic acid treatment increased insulin sensitivity through activation of Akt rather than AMPK signaling pathway while fruit juice of E. officinalis showed dual activation, Akt and AMPK as well.

Conclusion: These findings reveal the role of gallic acid in E. officinalis mediated antidiabetic potential, and delineate the upregulation of pAkt, PPAR-γ and Glut4 in gallic acid mediated antidiabetic activity, thus providing potential therapy for diabetes and related disorders.

Keywords: Adipogenesis; Db/db mice; Diabetes; Emblica officinalis; Gallic acid; High fructose diet; PPAR- γ.

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis / drug effects
  • Animals
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Fruit and Vegetable Juices
  • Gallic Acid / pharmacology*
  • Glucose / metabolism
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Hypoglycemic Agents / pharmacology*
  • Insulin Resistance
  • Male
  • Mice
  • Obesity / drug therapy
  • PPAR gamma / metabolism
  • Phyllanthus emblica / chemistry*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Signal Transduction / drug effects*

Substances

  • Glucose Transport Proteins, Facilitative
  • Hypoglycemic Agents
  • PPAR gamma
  • Gallic Acid
  • Proto-Oncogene Proteins c-akt
  • Glucose