Vanillic Acid Inhibits Inflammatory Pain by Inhibiting Neutrophil Recruitment, Oxidative Stress, Cytokine Production, and NFκB Activation in Mice

Abstract

Vanillic acid (1) is a flavoring agent found in edible plants and fruits. It is an oxidized form of vanillin. Phenolic compounds form a substantial part of plant foods used as antioxidants with beneficial biological activities. These compounds have received considerable attention because of their role in preventing human diseases. Especially, 1 presents antibacterial, antimicrobial, and chemopreventive effects. However, the mechanisms by which 1 exerts its anti-inflammatory effects in vivo are incompletely understood. Thus, the effect of 1 was evaluated in murine models of inflammatory pain. Treatment with 1 inhibited the overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone, the second phase of the formalin test, and complete Freund's adjuvant (CFA). Treatment with 1 also inhibited carrageenan- and CFA-induced mechanical hyperalgesia, paw edema, myeloperoxidase activity, and N-acetyl-β-D-glucosaminidase activity. The anti-inflammatory mechanisms of 1 involved the inhibition of oxidative stress, pro-inflammatory cytokine production, and NFκB activation in the carrageenan model. The present study demonstrated 1 presents analgesic and anti-inflammatory effects in a wide range of murine inflammation models, and its mechanisms of action involves antioxidant effects and NFκB-related inhibition of pro-inflammatory cytokine production.

Pyruvate dehydrogenase kinase 2 and 4 gene deficiency attenuates nociceptive behaviors in a mouse model of acute inflammatory pain

“…In conclusion, our findings suggest that PDK2 and PDK4 are indispensable in the pathogenesis of acute inflammation and subsequent nociception. At the site of inflammation, significantly enhanced expression of Pdk2 and Pdk4 mediates plasma extravasation and the activation and recruitment of neutrophils that can amplify inflammation and subsequent nociception via production of proinflammatory mediators (Liou et al, 2013;Jha et al, 2014;Tecchio et al, 2014;Calixto-Campos et al, 2015) and lactic acid (Sheikh et al, 2000;Bensel et al, 2011;Jha et al, 2015b), as reported earlier. As a consequence of peripheral noxious stimulation, the spinal dorsal horn displays glial activation as well as neuronal excitability, thereby leading to the central sensitization that amplifies nociceptive behaviors.…”

Vanillic acid attenuates obesity via activation of the AMPK pathway and thermogenic factors in vivo and in vitro

“…VA is also a constituent of wine, vinegar, and argan oil (20). It has antioxidant, antiinflammatory, and anticancer pharmacologic properties (21,22). A study by Hsu and Yen (23) showed that VA caused inhibition of intracellular TG in 3T3-L1 adipocytes.…”

The Effects and Mechanisms of Cyanidin-3-Glucoside and Its Phenolic Metabolites in Maintaining Intestinal Integrity

“…VA and FA represent the bioactive phenolic metabolites based on recent studies. VA may suppress the generation of reactive oxygen species (ROS) [42] and lipid peroxidation [32], potentially by increasing the activity of antioxidant enzymes such as SOD, CAT, and GPx [43,44], as well as the level of antioxidants such as vitamin E [43,44], vitamin C [43,44], and glutathione (GSH) [45] in mice, hamster, and diabetic hypertensive rats. Additionally, VA can inhibit the production of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, and IL-33 by down-regulating caspase-1 and NF-κB pathways [45][46][47] in mice or mouse peritoneal macrophages and mast cells.…”