Influence of Resveratrol on the Immune Response

Abstract

Resveratrol is the most well-known polyphenolic stilbenoid, present in grapes, mulberries, peanuts, rhubarb, and in several other plants. Resveratrol can play a beneficial role in the prevention and in the progression of chronic diseases related to inflammation such as diabetes, obesity, cardiovascular diseases, neurodegeneration, and cancers among other conditions. Moreover, resveratrol regulates immunity by interfering with immune cell regulation, proinflammatory cytokines' synthesis, and gene expression. At the molecular level, it targets sirtuin, adenosine monophosphate kinase, nuclear factor-κB, inflammatory cytokines, anti-oxidant enzymes along with cellular processes such as gluconeogenesis, lipid metabolism, mitochondrial biogenesis, angiogenesis, and apoptosis. Resveratrol can suppress the toll-like receptor (TLR) and pro-inflammatory genes' expression. The antioxidant activity of resveratrol and the ability to inhibit enzymes involved in the production of eicosanoids contribute to its anti-inflammation properties. The effects of this biologically active compound on the immune system are associated with widespread health benefits for different autoimmune and chronic inflammatory diseases. This review offers a systematic understanding of how resveratrol targets multiple inflammatory components and exerts immune-regulatory effects on immune cells.

Keywords: B lymphocytes; T lymphocytes; immune response; macrophages; natural killer; resveratrol.

Figure 1

Activity of resveratrol against different human diseases based on experimental studies.

Figure 2

Resveratrol pathways in immune function: resveratrol activates Sirtuin-1 (Sirt1) inhibiting RelA acetylation and promotes inhibitor protein-κBα (IkBα) degradation, which decreases nuclear factor kappa B (NF-κB)-induced expression of tumor necrosis-alpha (TNF-α), interrleukin (IL)-1β, IL(-6), metalloproteases (MMPs), and cyclooxygenase Cox-2. Cyclic adenosine monophosphate (cAMP) levels trigger protein kinase A (PKA), which activates Sirt1. AMP-activated protein kinase (AMPK) controls the activity of Sirt1 by regulating the cellular levels of nicotinamide adenine dinucleotide (NAD⁺). In the downstream activation of AMPK, an increase of NAD⁺ levels induces Sirt1 activation, which promotes deacetylation and activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α).

Figure 3

Effects of resveratrol on immune cells: Breg, regulatory B cell; COX2, cyclooxygenase; FOXP3, forkhead box P-3; GM-CSF, granulocyte–macrophage colony-stimulating factor; IL-10, interleukin-10; IL-17, interleukin 17; IRAK, interleukin-1 receptor-associated kinase; LPS, lipopolysaccharide; MΦ, macrophage; MCP1, monocyte chemoattractant protein-1; NF-κB, nuclear factor-Kappa B; NLRP3, nod-like receptor family, pyrin domain containing 3; Nrf2, nuclear factor erythroid 2-related factor 2; RIP, receptor-interacting protein; PCs, plasma cells; PGE2, prostaglandin E2; Sirt1, silent mating type information regulation 2 homolog; STAT3, signal transducer and activator of transcription; TAMs, tumor associated macrophages; TBK1, TANK-binding kinase1; TGF-β1, transforming growth factor-β1; Treg, regulatory T cell; Th17, T helper 17; TRIF, toll-interleukin-1 receptor domain-containing adaptor inducing interferon; TLR-2, toll-like receptor-2; VEGF, vascular endothelial growth factor.