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

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Abstract

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.

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Abbreviations

CRS:

Chronic restraint stress

Akt:

Protein kinase B

TNF-α:

Tumor necrosis factor-α

HPA:

Hypothalamic pituitary axis

IL-1β:

Interleukin-1β

IL-1α:

Interleukin-1α

IL-6:

Interleukin-6

CA:

Caffeic acid

RSV:

Resveratrol

IKK-β:

IκB kinase

NF-κβ:

Nuclear factor kappa β

IFN-β:

Interferon-β

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Acknowledgments

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

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Authors and Affiliations

  1. Pharmacology Division, UGC-Center of Advanced Study (UGC-CAS), University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India

    Suprithi Choudhary, Ashish Mourya, Swati Ahuja, Sangeeta Pilkhwal Sah & Anil Kumar

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  1. Suprithi Choudhary
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  2. Ashish Mourya
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  3. Swati Ahuja
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  4. Sangeeta Pilkhwal Sah
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  5. Anil Kumar
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Correspondence to Sangeeta Pilkhwal Sah.

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Choudhary, S., Mourya, A., Ahuja, S. et al. Plausible anti-inflammatory mechanism of resveratrol and caffeic acid against chronic stress-induced insulin resistance in mice. Inflammopharmacol 24, 347–361 (2016). https://doi.org/10.1007/s10787-016-0287-y

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