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The Bioactivity and Toxicological Actions of Carvacrol
Abstract and Figures
ABSTRACT Carvacrol is a monoterpenic phenol produced by an abundant number of aromatic plants, including thyme and oregano. Presently, carvacrol is used in low concentrations as a food flavoring ingredient and preservative, as well as a fragrance ingredient in cosmetic formulations. In recent years, considerable research has been undertaken in an effort to establish the biological actions of carvacrol for its potential use in clinical applications. Results from in vitro and in vivo studies show that carvacrol possess a variety of biological and pharmacological properties including antioxidant, antibacterial, antifungal, anticancer, anti-inflammatory, hepatoprotective, spasmolytic, and vasorelaxant. The focus of this review is to evaluate the existing knowledge regarding the biological, pharmacological, and toxicological effects of carvacrol.
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... In our study, carvacrol, which was examined to determined its protective effect against potential ovarian injury and infertility caused by cisplatin, is a monoterpene phenol obtained from Thymus vulgaris and Origanum vulgare [9]. As a result of in vitro and in vivo investigations of carvacrol, it has been revealed that it has antioxidant, antibacterial, antifungal, anticancer, anti-inflammatory and spasmolytic effects [10]. Gursul et al. showed that carvacrol increased total glutathione (tGSH) in methanol-induced liver injury [11].It has also been reported that it has an inhibitory effect on the formation of malondialdehyde (MDA), a proinflammatory cytokine and lipid peroxidation (LPO) product [12]. ...
... In recent years, significant research has been conducted to determine the biological effects of carvacrolregarding its probable use in clinical implementations. Findings from in vitro and in vivo research have shown that carvacrol hadsa variety of biological and pharmacological features, including vasorelaxant, antibacterial, antifungal, anticancer, hepatoprotective, anti-inflammatory, antioxidant, and spasmolytic properties [10,23]. ...
Objective:
In women, agents used in chemotherapy treatment have side effects such as accelerating follicular depletion and early menopause. Thus, cytotoxic treatments may cause various effects ranging from partial damage to the ovary to premature ovarian failure (POI) and infertility. This study aimed to investigate the protective effect of carvacrol on cisplatin (CIS)-induced reproductive toxicity in female rats.
Materials and methods:
The animals were divided to four groups; a healthy group (HG), administered only cisplatin 2.5 mg/kg (CIS); cisplatin 2.5 mg/kg + carvacrol mg/kg (CC-50), and cisplatin 2.5 mg/kg + carvacrol 100 mg/kg (CC-100). In this study, the CC-50 and CC-100 groups were injected with carvacrol at 50 and 100 mg/kg intraperitoneally (IP). The CIS and HG groupswere administered normal saline as a solvent in the same way. One hour afterwardthe CC-50 and CC-100 groups were injected with cisplatin at 2.5 mg/kg IP. This procedure was continued once a day for 14 days. At the end of this period, six rats from each group were euthanized with high-dose anaesthesia. Biochemical (oxidant-antioxidant and proinflammatory cytokines) and histopathological examinations were performed on the right ovarian tissue removed from the dead rats. The remaining (n = 6 in each group) animals were kept in the laboratory with mature male rats for two months for breeding. Rats that didn't give birth within two months were considered infertile. A one-way ANOVA test was used for the biochemical analysis, the a Kruskal Wallis test was used for the histopathological analysis.
Results:
It has been observed that cisplatine causes oxidative stress and inflammatory damage in the ovarian tissue of animals and ultimately causes infertility due to this oxidative stress. While carvacrol significantly suppressed cisplatin-related oxidative stress in ovarian tissue at the 50 and 100 mg/kg doses, it could suppress proinflammatory cytokine increase only at thecytokine increase only at the 100 mg/kg dose. In addition, carvacrol significantly reduced the development of cisplatin-related infertility (from 0 to 83.3%) at a dose of 100 mg/kg.
Conclusion:
These findings suggest that carvacrol at high doses can reduce the harmful effects of cisplatin on the ovary and improve ovarian reserve in rats.
... Carvacrol is one of the main components of M. chinensis Maxim, which has analgesic, anti-inflammatory, antiviral, insecticidal, and antioxidant effects (Suntres et al., 2015). It was demonstrated that carvacrol significantly reduced the lung index and the expression levels of IFN-γ, IL-2, IL-4, IL-5, and IL-10 in the lung tissue of FM1-infected C57BL/6 mice. ...
Influenza pneumonia has challenged public health and social development. One of the hallmarks of severe influenza pneumonia is overproduction of pro-inflammatory cytokines and chemokines, which result from the continuous activation of intracellular signaling pathways, such as the NF-κB pathway, mediated by the interplay between viruses and host pattern recognition receptors (PRRs). It has been reported that traditional Chinese medicines (TCMs) can not only inhibit viral replication and inflammatory responses but also affect the expression of key components of PRRs and NF-κB signaling pathways. However, whether the antiviral and anti-inflammatory roles of TCM are related with its effects on NF-κB signaling pathway activated by PRRs remains unclear. Here, we reviewed the mechanism of PRRs-mediated activation of NF-κB signaling pathway following influenza virus infection and summarized the influence of anti-influenza TCMs on inflammatory responses and the PRRs/NF-κB signaling pathway, so as to provide better understanding of the mode of action of TCMs in the treatment of influenza pneumonia.
... Some aromatic plants, like thyme and oregano, produce carvacrol (94), a monoterpene phenol (Figure 3d). Carvacrol is an additive in foods and cosmetics (Suntres et al., 2015). One study reported that carvacrol, isolated from Satureja thymbra, showed good antimicrobial activity (MICs = 12.5-50 μg/mL) against foodborne pathogens such as S. aureus, E. coli, and B. subtilis (Giweli et al., 2012). ...
Plant byproducts and waste present enormous environmental challenges and an opportunity for valorization and industrial application. Due to consumer demands for natural compounds, the evident paucity of novel antimicrobial agents against foodborne pathogens, and the urgent need to improve the arsenal against infectious diseases and antimicrobial resistance (AMR), plant byproduct compounds have attracted significant research interest. Emerging research highlighted their promising antimicrobial activity, yet the inhibitory mechanisms remain largely unexplored. Therefore, this review summarizes the overall research on the antimicrobial activity and inhibitory mechanisms of plant byproduct compounds. A total of 315 natural antimicrobials from plant byproducts, totaling 1338 minimum inhibitory concentrations (MIC) (in μg/mL) against a broad spectrum of bacteria, were identified, and a particular emphasis was given to compounds with high or good antimicrobial activity (typically <100 μg/mL MIC). Moreover, the antimicrobial mechanisms, particularly against bacterial pathogens, were discussed in-depth, summarizing the latest research on using natural compounds to combat pathogenic microorganisms and AMR. Furthermore, safety concerns, relevant legislation, consumer perspective, and current gaps in the valorization of plant byproducts-derived compounds were comprehensively discussed. This comprehensive review covering up-to-date information on antimicrobial activity and mechanisms represents a powerful tool for screening and selecting the most promising plant byproduct compounds and sources for developing novel antimicrobial agents.
... The major components were found to be oxygenated: piperitone, (Z)davanone, and 1,8-cineole. In this study, the Gram-positive MRSA showed the strongest lack of susceptibility in the MIC assay, while other research indicated that this strain is sensitive to many EOs and the carvacrol chemotype was mentioned as significantly active [12,27,30,48]. On the other hand, in the TLC-DB assay of this work, MRSA had the largest inhibition zones at R f = 0.51, identified as carvacrol. ...
Essential oils (EOs) with established and well-known activities against human pathogens might become new therapeutics in multidrug-resistant bacterial infections, including respiratory tract infections. The aim of this study was to evaluate the antimicrobial activity of EOs obtained from several samples of Origanum vulgare, O. syriacum, and O. majorana cultivated in Poland. EOs were analyzed by GC-MS and tested against four bacterial strains: Staphylococcus aureus (MRSA), Haemophilus influenzae, Haemophilus parainfluenzae, and Pseudomonas aeruginosa. Chemical analyses showed that the Eos were characterized by a high diversity in composition. Based on the chemical data, four chemotypes of Origanum EOs were confirmed. These were carvacrol, terpineol/sabinene hydrate, caryophyllene oxide, and thymol chemotypes. Thin-layer chromatography-bioautography confirmed the presence of biologically active antibacterial components in all tested EOs. The highest number of active spots were found among EOs with cis-sabinene hydrate as the major compound. On the other hand, the largest spots of inhibition were characteristic to EOs of the carvacrol chemotype. Minimal inhibitory concentrations (MICs) were evaluated for the most active EOs: O. vulgare 'Hirtum', O. vulgare 'Margarita', O. vulgare 'Hot & Spicy', O. majorana, and O. syriacum (I) and (II); it was shown that both Haemophilus strains were the most sensitive with an MIC value of 0.15 mg/mL for all EOs. O. majorana EO was also the most active in the MIC assay and had the highest inhibitory rate in the anti-biofilm assay against all strains. The most characteristic components present in this EO were the trans-sabinene hydrate and terpinen-4-ol. The strain with the least sensitivity was the MRSA with an MIC of 0.6 mg/mL for all EOs except for O. majorana, where the MIC value reached 0.3 mg/mL. Scanning electron microscopy performed on the Haemophilus influenzae and Haemophilus parainfluenzae biofilms showed a visible decrease in the appearance of bacterial clusters under the influence of O. majorana EO.
... Carvacrol is a monoterpenic phenol with a variety of biological properties, including antioxidant, antibacterial, antifungal, anticancer, anti-inflammatory, hepatoprotective, spasmolytic, and vasorelaxant [23]. A previous study demonstrated that carvacrol at a concentration of 0.63% was able to kill Psoroptes ovis after 12 h [22]. ...
The mite Sarcoptes scabiei is responsible for the emerging or re-emerging skin disease called scabies in humans and sarcoptic mange in animals. Essential oils represent an appealing alternative strategy for the control of Sarcoptes infections, but the commercial development of essential oils may be hampered by their inconsistency in efficacy due to their varied chemical compositions. In order to address this issue, we assessed the efficacy of six components (carvacrol, eugenol, geraniol, citral, terpinen-4-ol, and linalool) against S. scabiei. At a concentration of 0.5%, carvacrol presented the best miticidal efficacy, with a median lethal time (LT50) value of 6.7 min, followed by eugenol (56.3 min), geraniol (1.8 h), citral (6.1 h), terpinen-4-ol (22.3 h), and linalool (39.9 h). The LC50 values at 30 min for carvacrol, eugenol, and geraniol were 0.24, 0.79, and 0.91%, respectively. In conclusion, carvacrol, eugenol, and geraniol represent potential complementary or alternative agents for S. scabiei infections in humans or animals. Our study provides a scientific basis for the development of scabicidal products based on essential oils.
... www.nature.com/scientificreports/ antioxidant, anticancer, antibacterial, antifungal, anti-inflammatory, and hepatoprotective effects [26][27][28] . Previous studies showed that CAR provided neuroprotection against ischemia reperfusion-induced cerebral injury 29 , spinal cord injury 30 , and neurodegenerative disease 31 . ...
Traumatic brain injury (TBI) causes progressive dysfunction that induces biochemical and metabolic changes that lead to cell death. Nevertheless, there is no definitive FDA-approved therapy for TBI treatment. Our previous immunohistochemical results indicated that the cost-effective natural Iranian medicine, Satureja khuzistanica Jamzad essential oil (SKEO), which consists of 94.16% carvacrol (CAR), has beneficial effects such as reducing neuronal death and inflammatory markers, as well as activating astrocytes and improving neurological outcomes. However, the molecular mechanisms of these neuroprotective effects have not yet been elucidated. This study investigated the possible mechanisms involved in the anti-inflammatory and anti-apoptotic properties of SKEO and CAR after TBI induction. Eighty-four male Wistar rats were randomly divided into six groups: Sham, TBI, TBI + Vehicle, TBI + CAR (100 and 200 mg/kg), and TBI + SKEO (200 mg/kg) groups. After establishing the “Marmarou” weight drop model, diffuse TBI was induced in the rat brain. Thirty minutes after TBI induction, SKEO & CAR were intraperitoneally injected. One day after TBI, injured rats exhibited significant brain edema, neurobehavioral dysfunctions, and neuronal apoptosis. Western blot results revealed upregulation of the levels of cleaved caspase-3, NFκB p65, and Bax/Bcl-2 ratio, which was attenuated by CAR and SKEO (200 mg/kg). Furthermore, the ELISA results showed that CAR treatment markedly prevents the overproduction of the brain pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6. Moreover, the neuron-specific enolase (NSE) immunohistochemistry results revealed the protective effect of CAR and SKEO on post-TBI neuronal death. The current study revealed that the possible neuroprotective mechanisms of SKEO and CAR might be related to (at least in part) modulating NF-κB regulated inflammation and caspase-3 protein expression. It also suggested that CAR exerts more potent protective effects than SKEO against TBI. Nevertheless, the administration of SKEO and CAR may express a novel therapeutic approach to ameliorate TBI-related secondary phase neuropathological outcomes.
... Among its antimicrobial mechanisms, the potential to cause cell membrane depolarization by increasing its permeability, the reduction of cytoplasmic pH, the inhibition of ATP synthesis, and the increase of K+ efflux are highlighted. Its mechanisms, which basically act on the cell membrane, can improve the response to conventional antibiotics, enhancing their influx (Suntres et al., 2015). ...
The use of reactive diluents is undeniably of paramount importance to develop epoxy resins which would meet more demanding and restrictive processes and applications in terms of viscosity and glass transition temperature. In the context of developing resins with low carbon impacts, 3 natural phenols namely carvacrol, guaiacol and thymol were selected and converted into monofunctional epoxies using a general glycidylation procedure. Without advanced purification, the developed liquid-state epoxies showed very low viscosities of 16 cPs to 55 cPs at 20°C, which could be further reduced to 12 cPs at 20 °C when purification by distillation is applied. The dilution effect of each reactive diluent on DGEBA's viscosity was also assessed for concentrations ranging from 5 to 20 wt% and compared to commercial and formulated DGEBA-based resin analogues. Interestingly, the use of these diluents reduced the initial viscosity of DGEBA by a factor of ten while maintaining glass transition temperatures above 90 °C. This article provides compelling evidence of the possibility of developing new sustainable epoxy resins with characteristics and properties that can be fine-tuned by only adjusting the reactive diluent concentration.
Although several approaches for reducing antibiotic resistance genes (ARGs) in soil have been proposed, the application of environmentally friendly approaches is now attracting much more attention. In the present study, two types of essential oils (EOs), namely lavender essential oil (LEO) and oregano essential oil (OEO), were selected to investigate their roles in regulating ARGs in soil. In a 28-day microcosm experiment, it was found that the different types and doses of EOs significantly changed the composition of microbial communities. The LEO treatments enriched more taxa belonging to Actinobacteria than the control, whereas the low dose of OEO reduced Actinobacteria enrichment. Besides, the control and the treatments with a high dose of LEO and OEO all significantly enriched the functional pathways related to Human Diseases, which were positively associated with ARGs. However, the low dose of these EOs helped to reduce the pathways. Because of inhibition of the functional pathways and ARG hosts, the low dose of OEO reduce the ARGs related to antibiotic efflux by 71.8% and the resistance genes to multidrug by 56.4%, but these roles did not occur in LEO treatments. These outcomes provide practical and theoretical support for the application of EOs in remediating ARG-contaminated soils.
8β-Hydroxy-9(11),13-abietadien-12-one (1), an abietane diterpenoid and an aryl hydrocarbon receptor (AhR) ligand, was synthesized in six steps from commercially available (+)-dehydroabietylamine (2). We used the hypervalent iodine catalyst phenyliodine dicarboxylate, a safer alternative to toxic organoselenide reagents, for the oxidative dearomatization of ferruginol (7) to compound 1. Compounds 1 and 2, as well as the synthetic intermediates (compounds 3–7), were evaluated for AhR ligand activity. Only compounds 1 and 7 were active, which suggests that AhR affinity is influenced by the steric environment around the C-18 position of these compounds.
Food preservation is becoming more complex. New food products are being introduced onto the market. Generally these require longer shelf-lives and greater assurance of freedom from foodborne pathogenic organisms. The search for new substances to be used in food preservation is hampered by regulatory restrictions. Consequently a great deal of time and money may be required to develop a new chemical preservative and to get it approved especially in view of the public pressure against chemical additives in general. Such obstacles provide new opportunities for those seeking alternative routes in the search for new food preservatives. The excessive use of chemical preservatives, some of which are suspect because of their supposed or potential toxicity, has resulted in increasing pressure on food manufacturers to either completely remove chemical preservatives from their food products or to adopt more ‘natural’ alternatives for the maintenance or extension of a product’s shelf life. There is considerable interest in the possible use of such natural alternatives as food additives either to prevent the growth of foodborne pathogens or to delay the onset of food spoilage. Many naturally occurring compounds, such as phenols (phenolic acid, polyphenols, tannins), and organic acids (acetic, lactic, citric) have been considered in this context. Many spices and herbs and extracts possess antimicrobial activity, almost invariably due to the essential oil fraction (Deans and Ritchie, 1987). Thus the essential oils of citrus fruits exhibit antibacterial activity to foodborne bacteria (Dabbah et al., 1970) and moulds (Akgul and Kivanc, 1989) so too have the essential oils of many other plants such as oregano, thyme (Salmeron et al., 1990;Paster et al., 1990), sage, rosemary, clove, coriander etc. (Farag et al., 1989; Aureli et al., 1992; Stecchini et al., 1993). The antibacterial and antimycotic effects of garlic and onion have been well documented also (Mantis et al., 1978; Sharma et al., 1979; Saleem and Al-Delaimy, 1982; Conner and Beuchat, 1984a,b).
The minimum inhibitory concentrations (MIC) of 60 terpenoids against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Candida albicans have been determined. Hierarchical cluster analysis was used to group the compounds into five groups according to their activity patterns against the four microorganisms. K-Means cluster analysis was then used to confirm these groupings and to show the differences in the activity patterns of the groups. Ten molecular properties of the terpenoids, either calculated via molecular modelling or determined by direct measurement, were then used as variables in a forward stepwise discriminant analysis to identify which variables discriminated between groups. Low water solubility of Group IV compounds, mainly hydrocarbons and acetates, was found to be associated with their relative inactivity. The remaining groups, all containing oxygenated terpenoids, showed characteristic but distinct activity patterns towards the four test organisms. Hydrogen bonding parameters were found to be associated with antimicrobial activity in all cases. Activity against Gram-negative E. coli and P. aeruginosa was associated with a combination of a hydrogen bonding and size parameters. This was not found to be the case for the Gram-positive S. aureus or the yeast C. albicans. Copyright © 1999 John Wiley & Sons, Ltd.
During human development impressive changes in drug disposition occur. An important determinant of drug clearance is metabolism, something that is not only determined by ontogenic regulation but also by genetic processes which add to the variability of drug metabolism during different stages of childhood. Therefore, an understanding of the developmental regulation of different metabolic pathways, together with information on the genetic determinants of drug metabolism, will increase the knowledge of inter- and intraindividual variability in drug disposition during childhood. Conjugation has historically received less attention than cytochrome P450 metabolism. An important group of conjugation reactions are catalysed by the uridine 5′-diphosphate (UDP)-glucuronosyltransferases (UGTs); to date at least 10 different UGT isoforms have been identified. The UGTs are not only involved in the metabolism of many drugs [e.g. morphine, paracetamol (acetaminophen)] but also capable of the biotransformation of important endogenous substrates (e.g. bilirubin, ethinylestradiol) and several xenobiotics. Isoform specificity for these substrates has, however, not been fully characterised. Serious adverse events associated with chloramphenicol toxicity in the neonate have highlighted the importance of developmental changes in UGT activity. However, isoform-specific differences preclude the generalisation of a simple developmental pattern for UGT activity. UGT2B7 is the only UGT isoform for which ontogeny has been characterised both in vitro and in vivo, using morphine as the probe drug. However, no general developmental pattern for the individual UGT isoforms which might be of value for the clinician is currently available. Genetic polymorphisms have been identified for the UGT family. Not only for the UGT1A gene, which reduces bilirubin glucuronidation, leading to genetic hyperbilirubinaemia (the Crigler-Najjar and Gilbert’s syndromes), but also for 3 other UGT isoforms. However, the impact of these genetic differences on drug metabolism remains to be established because of overlapping isoform specificity of the drugs studied, as well as a lack of specific probe substrates to test the activity of individual UGT isoforms in relation to these gene mutations. Clearly, an information gap exists regarding the developmental and genetic aspects of UGT regulation and its potential impact on therapy. More research is needed on the pharmacogenetics and ontogeny of the UGTs for effective translation of scientific information into clinically applicable knowledge.