Phenolic Monoterpene Research Articles

IL-17/Notch1/STAT3 Pathway Contributes to 5-Fluorouracil-Induced Intestinal Mucositis in Rats: Amelioration by Thymol Treatment.

5-Fluorouracil (5-FU) is an anticancer drug with intestinal mucositis (IM) as a deleterious side effect. Thymol is a monoterpene phenol which has been reported to possess an antioxidant and anti-inflammatory activity versus 5-FU-induced IM. The Notch pathway affects multiple cellular activities, such as cellular proliferation, in addition to inflammatory responses modulation. Accordingly, this work was carried out in order to elucidate the role of the Notch pathway in 5-FU-induced IM and to further elucidate the immunomodulatory protective mechanisms of thymol. Experimental rats were divided randomly into four groups: Control, 5-FU, 5-FU+thymol (60 mg/kg/day), and 5-FU+thymol (120 mg/kg/day). 5-FU was injected intraperitoneally at a dose of 150 mg/kg on days 6 and 7, while thymol was orally administered daily for 11 days. By the end of the study, intestinal tissues were collected for the determination of IL-17, CD4, CD8, Notch1, Hes-1, pSTAT3, and STAT-3 protein expressions. The effect of thymol on 5-FU cytotoxicity was also examined using WST1 assay. 5-FU induced a marked increase in IL-17 levels, along with a marked downregulation of CD4 and the upregulation of CD8, Notch1, Hes-1 protein expressions, and activation of STAT3 in the intestinal tissue when compared with the control group. Thymol ameliorated the changes that occurred in these parameters. Additionally, cytotoxicity testing revealed that thymol augmented the antiproliferative action of 5-FU against breast and colorectal human cancer cell lines. This study was the first to show that the IL-17/Notch1/STAT3 pathway is involved in the molecular mechanism of 5-FU-induced IM, as well as the immunomodulatory activity of thymol.

Protective Effects of Natural Antioxidants on Inflammatory Bowel Disease: Thymol and Its Pharmacological Properties.

Inflammatory bowel disease (IBD) is a gastrointestinal disease that involves chronic mucosal or submucosal lesions that affect tissue integrity. Although IBD is not life-threatening, it sometimes causes severe complications, such as colon cancer. The exact etiology of IBD remains unclear, but several risk factors, such as pathogen infection, stress, diet, age, and genetics, have been involved in the occurrence and aggravation of IBD. Immune system malfunction with the over-production of inflammatory cytokines and associated oxidative stress are the hallmarks of IBD. Dietary intervention and medical treatment suppressing abnormal inflammation and oxidative stress are recommended as potential therapies. Thymol, a natural monoterpene phenol that is mostly found in thyme, exhibits multiple biological functions as a potential adjuvant for IBD. The purpose of this review is to summarize current findings on the protective effect of thymol on intestinal health in the context of specific animal models of IBD, describe the role of thymol in the modulation of inflammation, oxidative stress, and gut microbiota against gastrointestinal disease, and discuss the potential mechanism for its pharmacological activity.

Insights on biorational potential of Ocimum gratissimum essential oil and its binary combination with monoterpene phenol for control of rice weevil (Sitophilus oryzae) and aflatoxigenic fungi.

Food grain storage is a difficult task due to insect infestation and subsequent mycotoxin contaminations which adversely affects the nutritional quality of grains and leading to economic loss. Current research focuses on contact and fumigant toxicity effects of essential oils (EO) and aroma compounds against Sitophilus oryzae and growth inhibition of aflatoxigenic fungi. The EO of Ocimum gratissimum comprised of thymol (46.8%), γ-terpinene (14.04%) along with o-cymene (11.76%). Also, Cymbopogon flexuosus rich in citral (76.3%) and geraniol (84.6%) and Cymbopogon nardus having geraniol (49.24%) and geranyl acetate (20.9%) were all evaluated using a dose of 25 μL (Conc∼833.3 μL/L air) against S. oryzae. All the compounds showed significant mortality (>95%) at 24 h of exposure. The insecticidal property of O. gratissimum oil chemotype showed a strong contact and fumigant toxicity against S. oryzae at a highest dose of 25 μL (Conc∼833.3 μL/L air) within 24 h. It has been further evaluated on three aflatoxigenic fungal strains which showed reduction in growth and aflatoxin content (Aflatoxin B and G), which was markedly reduced upon the treatment. The binary mixture interaction of O. gratissimum oil with monoterpene phenol (carvacrol) was assessed and the specific binary mixture of 80:20 ratio (having additive property) acts as a contact insecticide with 100% mortality. Hence, essential oil of less explored Ocimum species (O. gratissimum) and its binary mixture could be deployed as potential biorational for control of rice weevil (Sitophilus oryzae) and aflatoxigenic Aspergillus spp.

Beneficial Effects of Carvacrol on In Vitro Models of Metabolically-Associated Liver Steatosis and Endothelial Dysfunction: A Role for Fatty Acids in Interfering with Carvacrol Binding to Serum Albumin.

Carvacrol, a plant phenolic monoterpene, is largely employed as food additive and phytochemical. We aimed to assess the lipid lowering and protective effects of carvacrol in vitro using cellular models of hepatic steatosis and endothelial dysfunction. We also investigated if and how the binding of carvacrol to albumin, the physiological transporter for small compounds in the blood, might be altered by the presence of high levels of fatty acids (FAs). Hepatic FaO cells treated with exogenous FAs mimic hepatosteatosis; endothelial HECV cells exposed to hydrogen peroxide are a model of endothelial dysfunction. In these models, we measured spectrophotometrically lipid accumulation and release, lipoperoxidation, free radical production, and nitric oxide release before and after treatment with carvacrol. The carvacrol binding to albumin in the presence or absence of high levels of FAs was assessed by absorption and emission spectroscopies. Carvacrol counteracted lipid accumulation and oxidative stress in hepatocytes and protected endothelial cells from oxidative stress and dysfunction. Moreover, high levels of FAs reduced the binding of carvacrol to albumin. The results suggest the good potential of carvacrol in ameliorating dysfunction of hepatic and endothelial cells in vitro. High levels of circulating FAs might compete with carvacrol for binding to albumin thus influencing its transport and bio-distribution.

Antifungal activity and mechanism of thymol against Fusarium oxysporum, a pathogen of potato dry rot, and its potential application

Dry rot is a major disease of potato during storage, which is caused by several Fusarium species. Biological control based on natural bioactive compounds that inhibit tuber disease provides an attractive alternative because they are ecofriendly and low toxic. In this study, a monoterpene phenol thymol (2-isopropyl-5-methylphenol) was found to have an effective antifungal effect against Fusarium oxysporum, the pathogen of potato dry rot in vitro and in vivo. After thymol treatment, the inhibition of mycelial growth was dose-dependent with thymol concentration, and the mycelial bending was obvious. The IC50 was 26.4 mg/L, and 80 mg/L thymol almost completely inhibited the growth of F. oxysporum. At 20 and 60 mg/L thymol, the spore germination rate of F. oxysporum decreased by 40 % and 80 % respectively compared with the control group. The pathogenicity and spore viability of F. oxysporum was significantly reduced after the treatment of thymol, while thymol did not alter chitin deposition. In addition, thymol could also improve the sensitivity of F. oxysporum to environment stresses (high/low temperature, UV, etc.) and induce the potato pieces to resist F. oxysporum. Furthermore, thymol had synergistic and additive effect on F. oxysporum with chemical fungicides mancozeb and carbendazim, respectively. A total of 370 differentially expressed genes (DEGs) were obtained from F. oxysporum treated with or without thymol. The analysis of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that DEGs were mainly related to metabolism, transport, membranes, etc. In general, this study provides a new idea for the development of thymol as an eco-friendly agent for the control of potato dry rot.

Stachys pilifera Benth: A Review of Its Botany, Phytochemistry, Therapeutic Potential, and Toxicology

Background Stachys L. (Lamiaceae) includes more than 300 annual or perennial species growing in temperate regions of Southern Africa, the Mediterranean, America, and Asia. Stachys pilifera Benth (S. pilifera), also known as Marzeh Kuhi, is an endemic species from Iran. It is found in the mountainous habitats of the Zagros area. It has various traditional uses, and the phytochemical ingredients and some biological activities of this species have been examined in previous studies. Methods PubMed, Science Direct, Google Scholar, Scopus, and Science Web databases were used to gather the data. The purpose of this review is to consolidate the scattered knowledge reported in the literature about botany, traditional uses, phytochemistry, pharmacological properties, and safety of S. pilifera and suggest its potential medicinal properties. Key Findings. In traditional Iranian medicine, S. pilifera manages various illnesses, such as rheumatoid arthritis, common cold, infections, asthma, and tussive. More than 30 compounds have been identified in S. pilifera essential oil. The compounds found in S. pilifera are phenolic compounds, monoterpenes, sesquiterpenes, flavonoids, alkaloids, and terpenoids, which have various properties such as antioxidant, nephroprotective, anti-inflammatory, antimicrobial, hepatoprotective, and anticancer properties. Conclusions The literature reveals that S. pilifera is an essential source of bioactive phytochemicals and illustrates the unknown area of this plant for new investigations. Moreover, we recommend that future research focus on toxicology and quality control studies for S. pilifera to fill the knowledge gap and provide theoretical support for the plant's possible functional and clinical uses.

The protective effects of thymol and carvacrol against di (2-ethylhexyl) phthalate-induced cytotoxicity in HEK-293 cells.

The protective effects of thymol and carvacrol, two phenolic monoterpenes with a wide spectrum of pharmacological effects, against the oxidative stress produced by the di (2-ethylhexyl) phthalate (DEHP) in human embryonic kidney cells 293 cells (HEK-293 cells) were investigated in this study. The cytotoxicity was monitored by cell viability, while oxidative stress generation was assessed by reactive oxygen species (ROS) quantification, antioxidant enzyme activities measurement, glutathione concentration, and malondialdehyde (MDA) quantification. The genotoxicity was evaluated by the measurement ofDNA fragmentation through the Comet assay. Our results demonstrated that the pretreatment of HEK-293 cells with thymol or carvacrol, 2 h before DEHP exposure, significantly increased the cell viability, decreased the ROS overproduction, modulated catalase (CAT), and superoxide dismutase (SOD) activities, restored the reduced glutathione content, and reduced the MDA level. The DNA fragmentation was also decreased by thymol and carvacrol pretreatment. These findings suggest that thymol and carvacrol could protect HEK-293 cells from DEHP-induced oxidative stress.

Carvacrol Suppresses Human Osteosarcoma Cells via the Wnt/β-Catenin Signaling Pathway.

Carvacrol is a monoterpenic phenol extracted from traditional Chinese herbs, including oregano and thyme. Currently, carvacrol has been widely studied for its therapeutic role in central nervous system diseases, liver diseases and digestive system cancer. However, the role of carvacrol in osteosarcoma and its underlying molecular mechanism remain elusive. Here, we aimed to examine the anticancer effects of carvacrol on osteosarcoma. The effects of carvacrol on the osteosarcoma proliferation capacity were revealed by CCK-8 and colony formation assays. Flow cytometry and Hoechst assays were used to determine the effects of carvacrol on osteosarcoma cell apoptosis. The effect of carvacrol on migration and invasion of osteosarcoma cells was determined by wound healing and transwell tests. Protein expression was evaluated by WB assays. The suppressive effects of carvacrol on osteosarcoma in vivo were examined by a xenograft animal model, immunohistochemistry and HE staining. We demonstrated that carvacrol treatment reduced viability and inhibited the colony formation of U2OS and 143B cells in a concentration-dependent manner. Apoptotic cell number increased after exposure to carvacrol. Meanwhile, the expression of Bax increased, and that of Bcl-2 decreased by carvacrol treatment. In addition, the MMP-9 expression and migration and invasion of 143B and U2OS cells were inhibited by carvacrol. We also found that these carvacrol-induced effects on osteosarcoma are associated with the regulation of the Wnt/β-catenin signaling pathway. Our findings suggest that carvacrol suppresses proliferation, migration, invasion and promotes apoptosis in osteosarcoma cells, in part by regulating the Wnt/β-catenin signaling pathway.

GENUS MELALEUCA: PHYTOCHEMISTRY, PHARMACOLOGY AND EFFECT AGAINST COVID-19

Medicinal plants are used for the prevention and treatment of many diseases as they are rich in phytochemical constituents (like terpenes, flavonoids, and alkaloids) responsible for the pharmacological effects of these plants. Genus Melaleuca named the tea tree, belonging to the family Myrtaceae, is cultivated in Australia as well as in the Pacific and some regions of Asia. It has been employed in Australian traditional medicine for its broad antimicrobial activity because of its contents of phenolic compounds, monoterpenes, tannins, flavonoids, sesquiterpenes, and essential oils. Owing to the valuable uses of plants of genus Melaleuca, for different medical purposes, it was deemed interest to summarize the previous studies reported from 2004 to 2020 in the available literature about the phytochemistry and pharmacological potential of both volatile and non-volatile components of Melaleuca species. Accordingly, this article may help researchers work on plants of genus Melaleuca to promote clinical applications towards the development of novel drugs of diverse pharmacological activities, including inhibitory effects on COVID 19 obtained from Melaleuca species.

Plant Extract and Essential Oil Application against Food-Borne Pathogens in Raw Pork Meat.

Herbal and plant extracts are being applied for a wide range of foods against different types of food-borne pathogens. In the present study, ethanolic and aqueous extracts (2% w/v) from cranberry (Vaccinium macrocarpon) and pomegranate (Punica granatum L.) plants were applied alone or in combination with two essential oils (thyme and oregano in a concentration of 0.150 μg/g) in pork meatballs and their antimicrobial activity was estimated. The extracts exhibited promising results (aqueous and ethanolic extracts of pomegranate and cranberry in a food-compatible concentration of 2% w/v) were applied to raw pork meatball production and their antimicrobial activity was recorded versus Enterobacteriaceae, total mesophilic bacteria, yeasts/molds, Staphylococcus spp., Pseudomonas spp. and lactic acid bacteria (LAB). The outcome demonstrated that meatballs containing aqueous extracts of pomegranate were more resistant to spoilage compared to all the other samples since they were preserved for more days. The chemical profiles of plant extracts were determined through LC-QTOF/MS and the chemical composition of the essential oils applied was determined with the use of GC/MS in order to identify the substances involved in the observed antimicrobial activity. Phenolic acids (quinic acid, chlorogenic acid), monoterpenes (p-cymene, carvacrol, thymol, limonene), organic acids (citric acid) and phenols were the main constituents found in the plant extracts and essential oils applied. These extracts of plant origin could be used as natural preservatives in meat products, even in low concentrations.

Productivity and essential oil quality of Himalayan Thyme (Thymus linearis Benth.) in relation to plant densities and drying methods

ABSTRACT Thymus linearis (Benth. ex Benth), commonly known as Himalayan thyme, is used extensively in folk medicines, food-flavours due its extract and aromatic constituents. The impact of plant densities on dry herb productivity and quality essential oil of T. linearis, as well as the effect of drying procedures on essential oil quality, were investigated in this study. Six plant spacing and four drying methods were applied. The plant densities have significant effect on dry herb (p<0.1) and essential oil yield (p<0.01) of T. linearis. Total 28 compounds were identified, forming 95.1–98.9% of composition. Phenolic monoterpenoids (41.7–59.0%) and monoterpene hydrocarbons (29.8–47.5%); with thymol (36.6–53.9%), γ-terpinene (17.7–24.1%) and p-cymene (3.8–17.0%) were the major constituents. The yield of dry herb and essential oil in thyme influenced by plant densities. Results showed that narrower spacing produces higher grain and quality essential oils in thyme as compared to wider spacing.

The Beneficial Effect of Carvacrol in HL-1 Cardiomyocytes Treated with LPS-G: Anti-Inflammatory Pathway Investigations.

Carvacrol (CAR), a natural phenolic monoterpene, possesses different biological activities, such as anti-inflammatory and antioxidant activities. The current study aimed to evaluate the response of HL-1 cardiomyocytes to an inflammatory stimulus triggered by lipopolysaccharide from Porphyromonas gingivalis (LPS-G), alone or in co-treatment with CAR, to investigate the potential protective role of CAR in the inflammatory process through modulation of the TLR4/NFκB/NALP3/IL-1β pathway and ROS production. In an in vitro experiment, HL-1 cardiomyocytes were exposed to LPS-G and incubated with CAR. We evaluated the anti-inflammatory effect of CAR by the reduction in TLR4, NFκB, NALP3, and IL-1β expression using immunofluorescence staining. Western blot analysis also validated the modulation of the TLR4/NFκB/NALP3/IL-1β pathway. ROS analyses confirmed the protective effects of CAR. Our results suggest that CAR could provide a significant protection role against inflammatory stimulus generated by LPS-G, involving the suppression of the TLR4/NFκB/NALP3/IL-1β signaling pathway.

Thymol protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson\u2019s disease via inhibiting oxidative stress

BackgroundParkinson’s disease (PD) is a multifactorial movement disorder with the progressive degeneration of the nigrostriatal system that impairs patients’ movement ability. Oxidative stress has been found to affect the etiology and pathogenesis of PD. Thymol, a monoterpenic phenol, is one of the most important dietary constituents in thyme species. It has been used in traditional medicine and possesses some properties including antioxidant, free radical scavenging, anti-inflammatory. In this study, in vitro and in vivo experiments were performed with the thymol in order to investigate its potential neuroprotective effects in models of PD.MethodsThe present study aimed to evaluate the therapeutic potential of thymol in 6-hydroxydopamine (6-OHDA)-induced cellular and animal models of PD. ResultsPost-treatment with thymol in vitro was found to protect PC12 cells from toxicity induced by 6-OHDA administration in a dose-dependent manner by (1) increasing cell viability and (2) reduction in intracellular reactive oxygen species, intracellular lipid peroxidation, and annexin-positive cells. In vivo, post-treatment with thymol was protective against neurodegenerative phenotypes associated with systemic administration of 6-OHDA. Results indicated that thymol improved the locomotor activity, catalepsy, akinesia, bradykinesia, and motor coordination and reduced the apomorphine-caused rotation in 6-OHDA-stimulated rats. Increased level of reduced glutathione content and a decreased level of MDA (malondialdehyde) in striatum were observed in the 6-OHDA rats post-treated with thymol.ConclusionsCollectively, our findings suggest that thymol exerts protective effects, possibly related to an anti-oxidation mechanism, in these in vitro and in vivo models of Parkinson’s disease.

Synthesis and Evaluation of Bakuchiol Derivatives as Potent Anti-inflammatory Agents in Vitro and in Vivo.

Bakuchiol, a prenylated phenolic monoterpene derived from the fruit of Psoralen corylifolia L. (Buguzhi), is widely used to treat tumors, viruses, inflammation, and bacterial infections. In this study, we designed and synthesized 30 bakuchiol derivatives to identify new anti-inflammatory drugs. The anti-inflammatory activities of the derivatives were screened using lipopolysaccharide-induced RAW264.7 cells. To evaluate the anti-inflammatory activity of the compounds, we measured nitric oxide (NO), interleukin-6, and tumor necrosis factor-α production. Based on the screening results, compound 7a displayed more pronounced activity than bakuchiol and celecoxib. Furthermore, the mechanistic studies indicated that 7a inhibited pro-inflammatory cytokine release, which was correlated with activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway and blockade of the nuclear factor-κB/mitogen-activated protein kinase signaling pathway. The in vivo anti-inflammatory activity in zebrafish indicated that 7a inhibited NO and reactive oxygen species production in a dose-dependent manner. These results indicate that 7a is a potential candidate for development as an anti-inflammatory agent.

Supplementation of Carvacrol Attenuates Hippocampal Tumor Necrosis Factor-Alpha Level, Oxidative Stress, and Learning and Memory Dysfunction in Lipopolysaccharide-Exposed Rats

Background:Carvacrol is a natural phenolic monoterpene with anti-inflammatory and antioxidant bioactivities. Neuroinflammatory and oxidative stress responses play a crucial role in the pathogenesis of Alzheimer's disease. The present study examined the effect of carvacrol on brain tumor necrosis factor-alpha (TNF-α) level and oxidative stress as well as spatial learning and memory performances in lipopolysaccharide (LPS)-exposed rats.Materials and Methods:The rats were treated with either carvacrol (25 and 50 mg/kg) or Tween 80 for 2 weeks. Thereafter, LPS (1 mg/kg) or saline was intraperitoneally administered on days 15–19, 2 h before Morris water maze task, and treatments with carvacrol or Tween 80 were performed 30 min prior to behavioral testing. The level of TNF-α, lipid peroxidation, and total thiol concentration were measured in the hippocampus and cerebral cortex at the end of the experiment.Results:It was found that LPS-exposed rats exhibited spatial learning and memory dysfunction, which was accompanied by increased TNF-α level and lipid peroxidation, and decreased total thiol concentration in the hippocampus and/or cortex. Moreover, treatment with carvacrol at a dose of 25 mg/kg attenuated learning and memory impairments, decreased TNF-α and lipid peroxidation level in the hippocampus and cortex, and increased total thiol concentration in the cortex.Conclusion:Carvacrol exerts neuroprotective effects against LPS-induced spatial memory deficits through attenuating hippocampal TNF-α level and oxidative stress in rats.

Antifungal Carvacrol Loaded Chitosan Nanoparticles.

The increased prevalence and incidence of fungal infections, of which Candida albicans represents one of the most life-threatening organisms, is prompting the scientific community to develop novel antifungal molecules. Many essential oils components are attracting attention for their interesting antifungal activities. Given the chemical and physical characteristics of these compounds, the use of appropriate nanodelivery systems is becoming increasingly widespread. In this study, chitosan nanoparticles were prepared using an ionic gelation procedure and loaded with the phenolic monoterpene carvacrol. After a bioassay guided optimization, the best nanoparticle formulation was structurally characterized by means of different spectroscopic (UV, FTIR and DLS) and microscopy techniques (SEM) and described for their functional features (encapsulation efficiency, loading capacity and release kinetics). The antifungal activity of this formulation was assayed with different Candida spp., both in planktonic and biofilm forms. From these studies, it emerged that the carvacrol loaded nanoparticles were particularly active against planktonic forms and that the antibiofilm activity was highly dependent on the species tested, with the C. tropicalis and C. krusei strains resulting as the most susceptible.

The biosynthesis of thymol, carvacrol, and thymohydroquinone in Lamiaceae proceeds via cytochrome P450s and a short-chain dehydrogenase

Thymol and carvacrol are phenolic monoterpenes found in thyme, oregano, and several other species of the Lamiaceae. Long valued for their smell and taste, these substances also have antibacterial and anti-spasmolytic properties. They are also suggested to be precursors of thymohydroquinone and thymoquinone, monoterpenes with anti-inflammatory, antioxidant, and antitumor activities. Thymol and carvacrol biosynthesis has been proposed to proceed by the cyclization of geranyl diphosphate to γ-terpinene, followed by a series of oxidations via p-cymene. Here, we show that γ-terpinene is oxidized by cytochrome P450 monooxygenases (P450s) of the CYP71D subfamily to produce unstable cyclohexadienol intermediates, which are then dehydrogenated by a short-chain dehydrogenase/reductase (SDR) to the corresponding ketones. The subsequent formation of the aromatic compounds occurs via keto-enol tautomerisms. Combining these enzymes with γ-terpinene in invitro assays or invivo in Nicotiana benthamiana yielded thymol and carvacrol as products. In the absence of the SDRs, only p-cymene was formed by rearrangement of the cyclohexadienol intermediates. The nature of these unstable intermediates was inferred from reactions with the γ-terpinene isomer limonene and by analogy to reactions catalyzed by related enzymes. We also identified and characterized two P450s of the CYP76S and CYP736A subfamilies that catalyze the hydroxylation of thymol and carvacrol to thymohydroquinone when heterologously expressed in yeast and N. benthamiana Our findings alter previous views of thymol and carvacrol formation, identify the enzymes involved in the biosynthesis of these phenolic monoterpenes and thymohydroquinone in the Lamiaceae, and provide targets for metabolic engineering of high-value terpenes in plants.

Amelioration of oxidative damage parameters by carvacrol on methanol-induced liver injury in rats.

The methanol metabolite that causes hepatotoxicity is formic acid, generating reactive oxygen radical formation and cell damage. Carvacrol is an antioxidant monoterpenic phenol produced from Thymus vulgaris. This study aimed to investigate the effects of carvacrol on methanol-induced oxidative liver damage in rats. Eighteen rats were divided into three groups. Methotrexate was administered orally for 7 days to methotrexate+methanol (MTM) and methotrexate+methanol+carvacrol (MMC) groups. Methotrexate was given before methanol to cause methanol poisoning. Distilled water was given to the healthy group (HG) as a solvent. At the end of the 7th day, 20% methanol was administered orally at a dose of 3 g/kg to the MTM and MMC groups. Four hours after methanol administration, 50 mg/kg carvacrol was injected intraperitoneally into the MMC group. Animals were sacrificed 8 h after carvacrol injection. Biochemical markers were studied in the excised liver tissue and blood serum samples, and histopathological evaluations were made. Severe hemorrhage, hydropic degeneration, pycnosis, and mononuclear cell infiltration were observed in the liver of the MTM group. Additionally, the levels of malondialdehyde (MDA), total oxidant status (TOS), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly higher, and total glutathione (tGSH) and total antioxidant status (TAS) were significantly lower in the MTM group compared to HG (P<0.001). Carvacrol prevented the increase in MDA, TOS, ALT and AST levels with methanol and the decrease in tGSH and TAS levels (P<0.001), and alleviated the histopathological damage. Carvacrol may be useful in the treatment of methanol-induced liver damage.

Would carvacrol be a supporting treatment option effective in minimizing the deleterious effects of COVID-19?

The pathophysiological process of the disease, Covid-19, is mediated by innate immunity, with the presence of macrophages responsible for secreting type 1 and 6 interleukins (IL), tumor necrosis factor (TNF) leading to dilation of endothelial cells with a consequent increase in capillary permeability. The treatment of this disease has been much discussed, but the variability in the clinical picture, the difficulties for diagnosis and treatment, especially of those patients who have the most severe clinical condition of the disease. Immunization is an effective tool for controlling the spread and overload of health services, but its effectiveness involves high investments in the acquisition of inputs, development of vaccines, and logistics of storage and distribution. These factors can be obstacles for countries with lower economic, technological, and infrastructure indexes. Reflecting on these difficulties, we raised the possibility of adjuvant therapies with imminent research feasibility, as is the case with the use of carvacrol, a monoterpenic phenol whose has biological properties that serve as a barrier to processes mediated by free radicals, such as irritation and inflammation, due to its antioxidant action. Many authors highlighted the activity of carvacrol as a potent suppressor of COX-2 expression minimizing the acute inflammatory process, decreasing the release of some pro-inflammatory mediators such as IL-1β, TNF-α, PGE2. Anyway, the benefits of carvacrol are numerous and the therapeutic possibilities too. With this description, the question arises: would carvacrol be a supporting treatment option, effective in minimizing the deleterious effects of Covid-19? There is still a lot to discover and research.

Development and characterization of monoterpene loaded microemulsions as novel scolicidal agents.

Cystic echinococcosis (CE) is one of the most important zoonotic diseases. The primary treatment is surgery and chemical sterilization of the parasitic layers by injection of a scolicidal agent. Available scolicidals possess side effects, and may cause postoperative complications. Several studies reported the scolicidal properties of monoterpene phenols and alcohols such as carvacrol, thymol, and geraniol. The present study aimed to develop, characterize, and assess monoterpene loaded microemulsions as novel green scolicidals products. For this purpose, microemulsions composing 0.37%, 0.75%, and 1.5% of monoterpenoid(s), thymol, carvacrol, and geraniol, alone or in binary or ternary mixtures were formulated. Samples were analyzed by visual inspection, polarizing optical microscope, and dynamic light scattering (DLS). The stability of the samples was evaluated up to a 3-month storage. For the scolicidal bioassay, samples at different concentrations of 200, 100, 50, 25, and 10 μg/ml were added to wells containing 104 viable protoscoleces and mortality rates were recorded at 2, 5, 10, and 20 min after exposure. Results of the present study showed that microemulsions formulated with 0.75% of pure carvacrol or the binary mixture of thymol and carvacrol at 0.375% are promising scolicidal agents.