Resveratrol is a polyphenolic compound widely found in grapes, tiger nuts, peanuts and other plants. Its anti-inflammatory effects are mainly realized through the following mechanisms:
1. Inhibition of inflammatory signaling pathways
NF-κB signaling pathway:
Resveratrol prevents the degradation of IκBα by inhibiting the activity of IκB kinase (IKK), thus inhibiting the nuclear translocation and transcriptional activity of NF-κB, and reducing the expression of pro-inflammatory genes (e.g., TNF-α, IL-6. COX-2).
MAPK signaling pathway:
Resveratrol can inhibit the activity of MAPK kinases (e.g. MEK) and block the phosphorylation of MAPK isoforms such as p38. ERK1/2. and thus inhibit the production of pro-inflammatory cytokines.
JAK/STAT signaling pathway:
Resveratrol reduces the production of pro-inflammatory cytokines such as IFN-γ and IL-12 by inhibiting the activity of JAK kinase and blocking the phosphorylation and nuclear translocation of STAT protein.
2. Regulation of inflammatory mediators
Inhibit nitric oxide (NO) and iNOS:
Resveratrol inhibits lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) in macrophages and reduces NO production, thereby reducing inflammatory responses.
Inhibition of cyclooxygenase-2 (COX-2):
Resveratrol reduces the production of inflammatory mediators such as prostaglandin E2 (PGE2) by inhibiting the expression of COX-2.
3. Inhibition of inflammatory cytokines
Reduce the production of pro-inflammatory cytokines:
Resveratrol can significantly reduce the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6. etc. and inhibit the inflammatory cascade response.
Promote the production of anti-inflammatory cytokines:
Resveratrol can up-regulate the expression of anti-inflammatory cytokines such as IL-10 to balance the inflammatory response.
4. Inhibit inflammasome activation
NLRP3 inflammasome:
Resveratrol can inhibit the assembly and activation of NLRP3 inflammasome and reduce the secretion of IL-1β and IL-18. thus reducing the inflammatory response.
5. Regulation of oxidative stress
Scavenging free radicals:
Resveratrol has powerful antioxidant activity, which can scavenge hydroxyl radicals, superoxide anion and other reactive oxygen species (ROS), and reduce cell damage caused by oxidative stress.
Enhancement of antioxidant enzyme activity:
Resveratrol can increase the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), enhancing the antioxidant capacity of cells.
6. Inhibit inflammatory cell activation and infiltration
Inhibit neutrophil and macrophage chemotaxis:
Resveratrol can inhibit the migration of inflammatory cells to the site of inflammation and reduce cellular infiltration at the site of inflammation.
Inhibition of macrophage phagocytosis:
Resveratrol can inhibit the phagocytosis of macrophages and reduce the release of pro-inflammatory factors.
7. Regulation of immune cell function
Inhibition of T-cell activation:
Resveratrol can inhibit the proliferation and activation of T cells and reduce the differentiation of Th1/Th17 cells, thus attenuating immune-mediated inflammatory responses.
Regulation of dendritic cell (DC) function:
Resveratrol inhibits the maturation and antigen presentation function of DCs and reduces T cell activation.
8. Activation of anti-inflammatory signaling pathways
PPARγ receptor:
Resveratrol can act as an agonist of PPARγ, promoting the expression of anti-inflammatory genes and inhibiting the transcription of pro-inflammatory genes.
Nrf2 signaling pathway:
Resveratrol can activate the Nrf2 signaling pathway, up-regulate the expression of antioxidant genes (e.g. HO-1. NQO1), and enhance the antioxidant and anti-inflammatory capacity of cells.
9. Inhibit the activity of inflammation-related enzymes
Lipoxygenase (LOX):
Resveratrol can inhibit the activity of 5-LOX and 12-LOX and reduce the production of inflammatory mediators such as leukotrienes.
Phospholipase A2 (PLA2):
Resveratrol can inhibit the activity of PLA2. reduce the release of arachidonic acid, and thus inhibit the production of inflammatory mediators.
10. Regulation of inflammation-related microenvironment
Inhibit angiogenesis:
Resveratrol can inhibit the expression of angiogenic factors such as VEGF and reduce neovascularization at the site of inflammation, thus limiting the spread of inflammation.
Inhibition of extracellular matrix degradation:
Resveratrol can inhibit the activity of matrix metalloproteinases (MMPs), protect the integrity of the extracellular matrix, and reduce tissue damage caused by inflammation.