, Volume 24, Issue 6, pp 347–361 | Cite as

Plausible anti-inflammatory mechanism of resveratrol and caffeic acid against chronic stress-induced insulin resistance in mice

  • Suprithi Choudhary
  • Ashish Mourya
  • Swati Ahuja
  • Sangeeta Pilkhwal Sah
  • Anil Kumar
Original Article


Stress is associated with many diseases and dysfunctions, such as depression, cardiovascular alterations, immunological function disorder, inflammation, obesity, and insulin resistance. Stress-induced inflammation is associated with the genesis of insulin resistance. Stress activates hypothalamic pituitary adrenal axis, Renin Angiotensin System pathway, and sympatho-adrenal system, all of which are involved in the production of cytokines, causing the negative downregulation of insulin signaling either by phosphorylating serine residues of IRS or by inhibiting the activity of Akt leading to insulin resistance. In this study, male LACA mice (20–30 g) were subjected to 2 h of chronic restraint stress daily for 30 days at variable time. Resveratrol, caffeic acid, glibenclamide, and their combinations were administered 45 min prior to restraint stress daily for 30 days and their anti-inflammatory effect was examined on CRS-induced behavioral, biochemical, and metabolic alterations. Induction of stress in mice was evident by increased corticosterone and decreased bodyweight. Chronic restraint stress for 30 days developed insulin resistance characterized by hyperglycemia, hyperinsulinemia, increased glycosylated haemoglobin (HbA1c), and homeostasis model assessment of insulin resistance index, hyperlipidemia, increased inflammatory cytokines, and TNF-α. Treatment with resveratrol, caffeic acid, and their combinations has attenuated stress-induced insulin resistance by reducing inflammation.


Chronic restraint stress Insulin resistance Resveratrol Caffeic acid Glibenclamide 



Chronic restraint stress


Protein kinase B


Tumor necrosis factor-α


Hypothalamic pituitary axis








Caffeic acid




IκB kinase


Nuclear factor kappa β





Funding was provided by University Grants Commission (Grant No. F.20-33(12)/2012(BSR), New Delhi, India.


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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Suprithi Choudhary
    • 1
  • Ashish Mourya
    • 1
  • Swati Ahuja
    • 1
  • Sangeeta Pilkhwal Sah
    • 1
  • Anil Kumar
    • 1
  1. 1.Pharmacology Division, UGC-Center of Advanced Study (UGC-CAS)University Institute of Pharmaceutical Sciences, Panjab UniversityChandigarhIndia

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