Abstract: We examined the antioxidant propertiesin vitroand the antinociceptive effect of carvacrol (CARV) in several models of pain in mice. CARV presented a strong antioxidant potential according to the TRAP/TAR evaluation; it also presented scavenger activity against nitric oxide and prevented lipid peroxidationin vitro. In mice, when evaluated against acetic acid‐induced abdominal writhing, CARV (25, 50 and 100 mg/kg, i.p.) reduced (p < 0.001) the number of writhing compared to the control group, without opioid participation. In the formalin test, CARV also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin‐induced licking, with inhibition percentage values of 56.8% (100 mg/kg) for the neurogenic phase and 41.2% (25 mg/kg), 73.8% (50 mg/kg) and 99.7% (100 mg/kg) for the inflammatory phase. CARV also produced a significant inhibition of the pain caused by capsaicin (63.1, 67.1 and 95.8%,p < 0.001) and glutamate (46.4, 61.4 and 97.9%,p < 0.01). When assessed in a thermal model of pain, CARV (100 mg/kg, i.p.) caused a significant increase (p < 0.05) in the latency response on the hot‐plate test. Such results were unlikely to be provoked by motor abnormality. Together, these results indicate that the properties of CARV should be more thoroughly examined in order to achieve newer tools for management and/or treatment of painful conditions, including those related to pro‐oxidant states.

Background: It is estimated that one in five people worldwide faces a diagnosis of a malignant neoplasm during their lifetime. Carvacrol and its isomer, thymol, are natural compounds that act against several diseases, including cancer. Thus, this systematic review aimed to examine and synthesize the knowledge on the antitumor effects of carvacrol and thymol.Methods: A systematic literature search was carried out in the PubMed, Web of Science, Scopus and Lilacs databases in April 2020 (updated in March 2021) based on the PRISMA 2020 guidelines. The following combination of health descriptors, MeSH terms and their synonyms were used: carvacrol, thymol, antitumor, antineoplastic, anticancer, cytotoxicity, apoptosis, cell proliferation, in vitro and in vivo. To assess the risk of bias in in vivo studies, the SYRCLE Risk of Bias tool was used, and for in vitro studies, a modified version was used.Results: A total of 1,170 records were identified, with 77 meeting the established criteria. The studies were published between 2003 and 2021, with 69 being in vitro and 10 in vivo. Forty-three used carvacrol, 19 thymol, and 15 studies tested both monoterpenes. It was attested that carvacrol and thymol induced apoptosis, cytotoxicity, cell cycle arrest, antimetastatic activity, and also displayed different antiproliferative effects and inhibition of signaling pathways (MAPKs and PI3K/AKT/mTOR).Conclusions: Carvacrol and thymol exhibited antitumor and antiproliferative activity through several signaling pathways. In vitro, carvacrol appears to be more potent than thymol. However, further in vivo studies with robust methodology are required to define a standard and safe dose, determine their toxic or side effects, and clarify its exact mechanisms of action.This systematic review was registered in the PROSPERO database (CRD42020176736) and the protocol is available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176736.

Objectives: The treatment of wounds accounts for a considerable fraction of health expenses as well as serious socioeconomic problems. The use of natural substances stands out as a source of new therapeutic discoveries for the wound healing. Thus, this review compiled scientific findings on the applicability of carvacrol and thymol, or essential oils containing at least one of these compounds, for the treatment of wounds. Methods: This review was performed at PubMed, SCOPUS, Web of Science databases using keywords as wound healing, thymol/carvacrol and essential oils. Thirteen studies were selected for discussion. Key findings: Thymol/carvacrol was able to act in the three phases of wound healing. In the first phase, they showed modulatory effect of the inflammatory cytokines, oxidative stress and antimicrobial power. In the second phase, they promoted re-epithelialization, angiogenesis and development of granulation tissue. Finally, in the third phase, they improve the collagen deposition and modulated the growth of fibroblasts and keratinocytes. Conclusions: These compounds present a high potential for the development of new therapeutic for wound repair. However, dose, efficacy and safety of these compounds for the treatment of wounds, as well as the mechanisms by which those effects can be observed, are challenges for future studies.

Terpenes are natural compounds found in several organisms belonging to the animal and plant kingdoms. They constitute the largest class of natural products with > 55,000 known compounds structurally diversified. Several studies have attributed to this big family of compounds a range of pharmacological properties, such as anticancer, antimicrobial, antifungal, antiviral, antihyperglycemic, analgesic, anti-inflammatory and antiparasitic. In this review, the authors summarize therapeutic patent applications concerning the employment of terpenes for pain relief, focusing on the perspective for these compounds to become candidates for new drugs intended to control painful syndromes. Over years of tremendous academic and industrial investment in the characterization of the analgesic action of terpenes, there was the development of a successful product that has been well-accepted clinically. Furthermore, there is still hope that new therapeutic options for the control of painful syndromes will be developed from terpenes, which have been shown to be great candidates for this purpose because of the range of pharmacological mechanisms in important target sites.