Carvacrol attenuates mechanical hypernociception and inflammatory response

Abstract

Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 μg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.

Carvacrol protects neuroblastoma SH-SY5Y cells against Fe2+-induced apoptosis by suppressing activation of MAPK/JNK-NF-κB signaling pathway

“…Recently, an increasing number of studies have focused on its therapeutic potential in different diseases. It has been reported that carvacrol has a wide range of protective properties, including anti-inflammatory, antioxidant, antimicrobial, antitumor, and anti-hepatotoxic activities [23][24][25][26] . For example, studies have reported that carvacrol has the ability to protect the liver and brain against ischemia/reperfusion (I/R) injury in in vivo studies [27][28][29] .…”

The Effect of Carvacrol on Inflammatory Pain and Motor Coordination in Rats

“…In our study, carvacrol applied in the maximal tested dose of 100 mg /kg, did not disturb motor coordination in rats, and the applied dose did not produces visible clinical depression of the CNS. Similarly, the spontaneous locomotor activity of mice exposed to carvacrol (100 mg/ kg, IP) was not affected in the experiments performed by Guimarăes et al [12]. If it is known that the oral LD 50 of carvacrol in the rat is 810 mg /kg BW, and that the major toxic effects of monoterpenes are related to the disorder of CNS (20), it was expected that carvacrol in the highest tested dose (100 mg/kg) in our experiments is not able to alter the motor coordination in rats.…”

“…It has been shown that carvacrol administered orally in mice reduces formalin-induced nociception, mechanical hyperalgesia and infl ammation in damaged tissues [11]. Also, Guimaraes et al [12] demonstrated that carvacrol administered orally in mice exhibits signifi cant antinociceptive and anti-edematous activity on hyperalgesia and edema caused by carrageenan and tumor necrosis factor-alpha (TNF-α). However, carvacrol exhibits no effect on the hyperalgesia induced by prostaglandin E2 (PGE2) and dopamine.…”

Modulation of Cytokine Production and Transcription Factors Activities in Human Jurkat T Cells by Thymol and Carvacrol

“…8 In other studies administration of carvacrol or thymol has reduced TNF-α levels in pleural lavage, decreased the lipopolysaccharide (LPS)-induced nitrite production and suppressed autoimmune arthritis in experimental models. 9 The combination of carvacrol with methotrexate has also suppressed complete Freund's adjuvant induced synovial inflammation with reduced hepatotoxicity in rats. 10 Inflammatory responses are mainly controlled by T lymphocytes.…”