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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and difficult-to-treat symptoms in cancer patients. For this reason, the explore for unused helpful choices able of filling these impediments is essential. Natural products from plants stand out as a valuable source of therapeutic agents, being options for the treatment of this growing public health problem. Therefore, the objective of this study was to report the effects of natural products from plants and the mechanisms of action involved in the reduction of neuropathy caused by chemotherapy. The search was performed in PubMed, Scopus and Web of Science in March/2021. Two reviewers independently selected the articles and extracted data on characteristics, methods, study results and methodological quality (SYRCLE). Twenty-two studies were selected, describing the potential effect of 22 different phytochemicals in the treatment of CIPN, with emphasis on terpenes, flavonoids and alkaloids. The effect of these compounds was demonstrated in different experimental protocols, with several action targets being proposed, such as modulation of inflammatory mediators and reduction of oxidative stress. The studies demonstrated a predominance of the risk of uncertain bias for randomization, baseline characteristics and concealment of the experimental groups. Our findings suggest a potential antinociceptive effect of natural products from plants on CIPN, probably acting in several places of action, being strategic for the development of new therapeutic options for this multifactorial condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Santos, Guimarães, Pina, Serafini and Guimarães.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sampaio, Pina, Serafini, Tavares and Guimarães.)