Antitumor Effects of Carvacrol and Thymol: A Systematic Review

Abstract

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.

Antinociceptive effect of plant-based natural products in chemotherapy-induced peripheral neuropathies: A systematic review

“…In contrast, eight studies mentioned that a random allocation of animals was made and that investigators were blinded (n = 8, 36.36%) (Figure 3). Similar to our results, Toro et al (2019), Sampaio et al (2021), andPina et al (2021) demonstrated that preclinical studies in animals present insufficient information that Frontiers in Pharmacology frontiersin.org implies judgment of domains. In contrast, domains that include allocation and blinding of investigators are reported in most studies included in systematic reviews (Toro et al, 2019;Pina et al, 2021;Sampaio et al, 2021).…”

Ileum transcriptional response to prolonged supplementation with phytogenic product containing menthol, carvacrol and carvone

“…DNA topoisomerase II alpha (TOP2A) is associated with more than 200 cancer categories, and more than 100 registered drugs target this protein as inhibitors or chain breakers. Cancer is characterised with out of control cell growth cycle, and inhibition of these 7 cell cycle associated genes that already have a range of anticancer inhibitors developed, is in support of anticancer effects reported for all 3 major ingredients of the phytogenic product [ 13 , 27 , 45 ].…”

“…Carvacrol also has a range of benefits in addition to well documented antibacterial [ 17 ], anti–biofilm [ 18 , 19 ], antifungal [ 20 ], anticoccidial [ 21 ], anti-parasitic [ 22 ], antimalarial [ 23 ] and insecticide [ 24 , 25 , 26 ] abilities. In addition, carvacrol is a strong antitumor agent [ 27 ], especially against tumours related to sex hormones such as breast [ 28 ], cervical [ 29 ] and prostate. It alleviates oxidative and LPS induced stress [ 30 , 31 ], it is an anti-inflammatory and antioxidant in the respiratory system [ 32 ], strongly liver protective by slowing down liver fibrosis [ 33 ] and healing liver injury [ 34 ].…”

Status and Prospects of Botanical Biopesticides in Europe and Mediterranean Countries

“…The monoterpenes carvacrol, γ-terpinene, and thymol are known to disrupt the cell membrane and to influence several metabolic pathways, photosynthesis, cell respiration and mitosis [ 171 , 206 ]. However, there is not much known about the exact mechanism of carvacrol in plant metabolism [ 137 ], but it seems that this monoterpene deploys cytotoxic effects [ 191 , 207 ] that harm several plants. Similar to other monoterpenes, carvacrol has intense inhibitory effects on germination and seedling growth [ 179 ], suggesting that pathways other than photosynthesis are induced by carvacrol.…”