β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo

Abstract

Inflammation is a complex biological response involving the immune, autonomic, vascular, and somatosensory systems that occurs through the synthesis of inflammatory mediators and pain induction by the activation of nociceptors. Staphylococcus aureus, the main cause of bacteremia, is one of the most common and potent causes of inflammation in public health, with worse clinical outcomes in hospitals. Antioxidant substances have been evaluated as alternative therapeutic analgesics, antioxidants, anti-inflammatory agents, antitumor agents, and bactericides. Among these, we highlight the essential oils of aromatic plants, such as β-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The objective of this study was to evaluate the biological activities of BCP–DHA association in in vitro and in vivo experimental models of antinociception and inflammation. To determine the anti-inflammatory effects, monocytes isolated from the peripheral blood of adult male volunteers were infected with methicillin-resistant S. aureus and incubated with treatment for cytokine dosage and gene expression analysis. Antinociceptive effects were observed in the three models when comparing the control (saline) and the BCP-DHA treatment groups. For this purpose, the antinociceptive effects were evaluated in animal models using the following tests: acetic acid-induced abdominal writhing, paw edema induced by formalin intraplantar injection, and von Frey hypernociception. There was a significant reduction in the GM-CSF, TNFα, IL-1, IL-6, and IL-12 levels and an increase in IL-10 levels in the BCP-DHA treatment groups, in addition to negative regulation of the expression of the genes involved in the intracellular inflammatory signaling cascade (IL-2, IL-6, IRF7, NLRP3, and TYK2) in all groups receiving treatment, regardless of the presence of infection. Statistically significant results (p < 0.05) were obtained in the acetic acid-induced abdominal writhing test, evaluation of paw edema, evaluation of paw flinching and licking in the formalin intraplantar injection model, and the von Frey hypernociception test. Therefore, BCP and DHA, either administered individually or combined, demonstrate potent anti-inflammatory and antinociceptive effects.

Advances in the Phytochemical Characterisation and Bioactivities of Salvia aurea L. Essential Oil

“…β-Caryophyllene also exerted anti-inflammatory effects in colitis [ 79 ], skin wound excisions [ 80 ], and sepsis [ 81 ] in animal models. Other in vitro and in vivo approaches highlight the anti-inflammatory action of this sesquiterpene [ 82 , 83 ]. The results suggest that the activity observed in S. aurea could be due to the presence of these compounds, which might act synergistically.…”

β-Caryophyllene Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis through the Downregulation of Mitogen-Activated Protein Kinase/EGR1/TSLP Signaling Axis

“…Previous studies have demonstrated that BCP inhibits lipopolysaccharide-induced IL-1β, IL-6, and TNFα production in THP-1 human monocytic cells [ 34 ] and prevents high glucose-induced oxidative stress and inflammation through the inhibition of NF-κB and Nrf2 in mesangial cells [ 35 ]. Moreover, BCP reduces proinflammatory cytokine TNFα, IL-6, and IL-12 production through the inhibition of NLRP3 inflammasome in human peripheral blood mononuclear cells [ 36 ], and alleviated lipopolysaccharide-induced lung inflammation through the inhibition of transforming growth factor β-activated kinase 1 (TAK1)/MAPK-mediated signaling pathways [ 20 ]. These findings suggest that BCP exhibits anti-inflammatory features in various cells and tissues by targeting NF-κB-mediated pathways.…”