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Abstract

Carvacrol (CV) is a phenolic monoterpenoid found in essential oils of oregano (Origanum vulgare), thyme (Thymus vulgaris), pepperwort (Lepidium flavum), wild bergamot (Citrus aurantium bergamia), and other plants. Carvacrol possesses a wide range of bioactivities putatively useful for clinical applications such antimicrobial, antioxidant, and anticancer activities. Carvacrol antimicrobial activity is higher than that of other volatile compounds present in essential oils due to the presence of the free hydroxyl group, hydrophobicity, and the phenol moiety. The present review illustrates the state‐of‐the‐art studies on the antimicrobial, antioxidant, and anticancer properties of CV. It is particularly effective against food‐borne pathogens, including Escherichia coli, Salmonella, and Bacillus cereus. Carvacrol has high antioxidant activity and has been successfully used, mainly associated with thymol, as dietary phytoadditive to improve animal antioxidant status. The anticancer properties of CV have been reported in preclinical models of breast, liver, and lung carcinomas, acting on proapoptotic processes. Besides the interesting properties of CV and the toxicological profile becoming definite, to date, human trials on CV are still lacking, and this largely impedes any conclusions of clinical relevance.

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... [10][11][12] Carvacrol (CAR) is a liquid phenolic monoterpenoid, 2-methyl-5-(1-methylethyl) phenol and is present in essential oils obtained from different plants, such as oregano (Origanum vulgare), marjoram (Origanum majorana), and Mexican oregan (Lippia graveolens), among others. [13] CAR possess a wide range of biological activities including anti-inflammatory, antibacterial, antifungal, antioxidant, anticarcinogenic, antiplatelet, and vasorelaxant. [13,14] Despite the fact that the mechanisms of action of CAR are not well clarified and not well understood, some of them have been related to the reduction of the membrane potential which effect promoted a rise of the intracellular calcium concentration by inducing PLC-dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ entry through PKC-sensitive, non-store-operated Ca 2+ channels. ...
... [13] CAR possess a wide range of biological activities including anti-inflammatory, antibacterial, antifungal, antioxidant, anticarcinogenic, antiplatelet, and vasorelaxant. [13,14] Despite the fact that the mechanisms of action of CAR are not well clarified and not well understood, some of them have been related to the reduction of the membrane potential which effect promoted a rise of the intracellular calcium concentration by inducing PLC-dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ entry through PKC-sensitive, non-store-operated Ca 2+ channels. [15,16] Other findings have suggested that CAR possesses a vasorelaxant property that was tested in the rat aorta which effect has also been related to some mechanisms involving a transduction pathway between Ca 2+ release from sarcoplasmic reticulum and/or regulation of the Ca 2+ sensitivity of the contractile system. ...
... [18,22,23] Some aromatic plants-derived organic compounds that may be involved in the defense of plants against phytopathogenic bacteria, fungi, viruses, among others. [24] One of these compounds is CAR which can exhibit numerous bioactive properties in in vitro and in vivo models, [13] such as the neuroprotective property of CAR in conscious rodents through the activation of the receptor potential vanilloid 3 (TRPV3) channels. [25] Hence, to evaluate if the inhibition of the uterine contractions was a direct consequence of the inactivation of the receptor/voltage-operated Ca 2+ channels or of the inhibition of the synthesis of prostaglandins, controls of nifedipine, and indomethacin were used for comparison, since both tocolytic drugs inhibit the uterine contraction by blocking Ca 2+ channels and by inhibiting the cyclooxygenase, an enzyme that catalyzes the production of prostaglandins that are also known as a potent utero-tonic agent, respectively. ...
Article
Despite the wide application of carvacrol (CAR) in different biological and medical areas, there is still insufficient electrophysiological data on the mechanisms of action of CAR, particularly in the pregnant uterine function. The aim of this study was to evaluate the in vitro tocolytic effect of CAR on the contractility of isolated pregnant rat uterus in the presence of a calcium channel antagonist (nifedipine) and a cyclooxygenase inhibitor (indomethacin). The uteri were isolated from pregnant Wistar rats at 16-18 days of pregnancy and suspended in an isolated organ bath chamber containing a Ringer's physiological solution and aerated with 95% O2and 5% CO2. Samples were used in functional tests to evaluate the inhibitory effect of CAR at increasing concentrations on the rhythmic spontaneous, oxytocin-induced phasic, K+-induced tonic, and Ca2+-induced contractions. The differences in inhibitory concentration-50 and Emaxamong the compounds were determined using the one-way ANOVA followed by a post hoc Student-Newman-Keuls or Bonferroni test, in all casesP < 0.05 was considered statistically significant. Nifedipine was used as positive controls where required. CAR caused a significant concentration-dependent inhibition of the uterine contractions induced by the pharmaco- and electro-mechanic stimuli. We showed that the inhibitory effects of CAR depends on the type of muscle contraction stimuli, and that it acts stronger in spontaneous rhythmic activity and in contractions of isolated rat uterus induced by Ca2+. Nifedipine was more potent than CAR and indomethacin on the uterine contractility (P < 0.05), but none of them was more effective than nifedipine. Therefore, the tocolytic effect induced by CAR was associated with the blockade of the calcium channels in the pregnant rat uterus. This property placed CAR as a potentially safe and effective adjuvant agent in cases of preterm labor, an area of pharmacological treatment that requires urgent improvement.
... Administering more than one drug can provide many benefits: higher efficacy, lower toxicity, and at least delayed onset of acquired drug resistance [8][9][10]. Such compounds act on tumors by inducing cell death through different pathways [11,12]. Most of the studies on the cytotoxic effects of plant bioactive components are limited to the effect of single components, while their impact is normally due to the combination of multiple components. ...
... By preserving their morphology, sustaining their viability, promoting their proliferation, and protecting them from cytotoxicity and oxidative stress, PV appears to be a promising natural medicinal product for strengthening the therapeutic effects of MSCs [6]. Several studies have shown that carvacrol or thymol may individually induce, in vitro and in vivo (animal models), cancer cell death through the deregulation of different genes involved in cell proliferation and the apoptosis signaling pathway [11,12]. For leukemic cells, previous studies have shown that both carvacrol and thymol individually showed cytotoxic effects on the HL60 cell line by inducing apoptotic cell death [19,20]. ...
... In this context, carvacrol has been approved as a food additive by the Food and Drug Administration (FDA) and added in the list of chemical flavorings by the Council of Europe. It is known that carvacrol has several pharmacological properties including antioxidant, anti-inflammatory, immunomodulatory, antitumor, and antimicrobial effects [12]. A clinical study that was conducted to assess the effect of carvacrol on respiratory symptoms in the veterans exposed to sulfur mustard (SM) showed that two months of treatment with carvacrol reduced inflammatory cytokine and chemokine but increased anti-inflammatory cytokines. ...
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Acute myeloid leukemia (AML) is a cancer of the myeloid lineage of blood cells, and treatment for AML is lengthy and can be very expensive. Medicinal plants and their bioactive molecules are potential candidates for improving human health. In this work, we studied the effect of Ptychotis verticillata (PV) essential oil and its derivatives, carvacrol and thymol, in AML cell lines. We demonstrated that a combination of carvacrol and thymol induced tumor cell death with low toxicity on normal cells. Mechanistically, we highlighted that different molecular pathways, including apoptosis, oxidative, reticular stress, autophagy, and necrosis, are implicated in this potential synergistic effect. Using quantitative RT-PCR, Western blotting, and apoptosis inhibitors, we showed that cell death induced by the carvacrol and thymol combination is caspase-dependent in the HL60 cell line and caspase-independent in the other cell lines tested. Further investigations should focus on improving the manufacturing of these compounds and understanding their anti-tumoral mechanisms of action. These efforts will lead to an increase in the efficiency of the oncotherapy strategy regarding AML.
... Regular consumption of antioxidants as a part of nutraceuticals or dietary supplements at an appropriate dose helped to encounter and prevent the body from oxidative stress-related diseases [6]. Due to safety issues over long-term uses of synthetic antioxidants, the natural origin antioxidants are more preferred to formulate nutraceuticals and dietary supplements [7,8]. Therefore, identifying plants with potential antioxidant activity will significantly impact human health and economic benefit. ...
... Since plants are rich in bioactive compounds, there is a great prospect to discover new compounds or drugs having health-beneficial properties. Many phenolic and flavonoid compounds exhibiting beneficial health activities, such as antioxidant, antiinflammatory, anticancer, antihypertensive and anti-obesity, have been identified from the ethnomedicinal plants [8][9][10]. ...
... Plants are well known as a potential source of bioactive compounds, and such phytoorigin compounds are more preferred over synthetic ones [8]. Hence, researchers are looking for neglected or underutilized medicinally important edible plants to discover new bioactive compounds. ...
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Oxidative stress is the major cause of many health conditions, and regular consumption of antioxidants helped to encounter and prevent such oxidative stress-related diseases. Due to safety concerns over long-term uses of synthetic antioxidants, natural antioxidants are more preferred. The purpose of this study is to investigate the antioxidant and anticancer activities of Jussiaea repens L., a wild edible flora found in Manipur, India. The antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), Ferric reducing antioxidant power (FRAP) assay and DNA-nicking assay. The anticancer activity was tested using five cancer lines viz., SKOV3 cells (ovarian), HeLa (cervical), MDA-MB-231 (breast), PANC-1 (pancreatic), and PC3 (prostate). The toxicity, developmental effect, antiproliferative activity was further tested using zebrafish embryos. The methanolic plant extract had higher polyphenol content than flavonoids. The in vitro study demonstrated a promising antioxidant capacity and DNA protection ability of this plant. The extract also showed cytotoxic activity against SKOV3, HeLa, MDA-MB-23, and PANC-1 cancer cell lines. The in vivo studies on zebrafish embryos demonstrated the extract’s ability to suppress the developmental process and elicited more cytotoxicity to cancer cells than developing zebrafish embryos. Moreover, the in vivo studies on zebrafish embryos also indicated the antiproliferative activity of J. repens L. extract.
... The high concentrations of thymol, carvacrol, and p-cymene are consistent with the traditional uses of Monarda spp. to treat skin infections, wounds, fevers, and respiratory problems. Thymol [31], carvacrol [32], and p-cymene [33] have demonstrated antibacterial and antifungal activities [34,35], as well as wound-healing activity [36]. Thymol [37] and carvacrol [38], in addition to thymoquinone [39], have shown antitussive effects. ...
... Thymoquinone has also shown wound-healing properties [40]. Furthermore, both thymol [41] and carvacrol [32] have shown analgesic and anti-inflammatory activities [42]. ...
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The genus Monarda (family Lamiaceae) contains 22 species of which three are native to southern Alabama, M. citriodora, M. fistulosa, and M. punctata. Several species of Monarda have been used in traditional medicines of Native Americans, and this present study is part of an ongoing project to add to our understanding of Native American pharmacopeia. Plant material from M. citriodora, M. fistulosa, and M. punctata was collected in south Alabama and the essential oils obtained by hydrodistillation. The essential oils were analyzed by gas chromatographic techniques to determine the chemical compositions as well as enantiomeric distributions. The compounds thymol, carvacrol, p-cymene, and their derivatives were the primary terpenoid components found in the essential oils. The known biological activities of these compounds are consistent with the traditional uses of Monarda species to treat wounds, skin infections, colds, and fevers.
... It is found in the essential oils of many aromatic plants, including, among others, oregano, and thyme. CV is responsible for a wide range of pharmacologic activities, including antimicrobial, antioxidant, and anti-cancer activities (12). Remarkably, CV has high antioxidant activity, and numerous studies have investigated its antioxidant properties (13). ...
... It is also worth noting that CV is well known for its strong antioxidant properties compared to other essential volatile oils. The strong radical-scavenging activity of CV was proven in both in vitro and in vivo studies (12). It demonstrated a hepatoprotective effect in a hepatotoxicity study by increasing the activity of enzymatic (superoxide dismutase, catalase, and GSH peroxidase) and non-enzymatic (vitamin C and E) antioxidants (25). ...
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Objective: This study aimed to explore whether carvacrol (CV) had a protective effect on paclitaxel-induced ototoxicity from biochemical, functional, and histopathological perspectives. Methods: Forty Wistar albino male rats were randomly separated into five groups of eight rats. Group 1 was the control group, so Paclitaxel or CV was not administered. Group 2 was administered i.p. CV at 25 mg/kg once a week; Group 3, was administered i.p. paclitaxel at 5 mg/kg once a week; Group 4 was administered i.p. paclitaxel at 5 mg/kg followed (30 min later) by CV at 25 mg/kg once a week; and Group 5 was administered i.p. CV at 25 mg/kg followed (1 day later) by paclitaxel at 5 mg/kg. once a week. The drugs were administered intraperitoneally once a week for four consecutive weeks, and distortion product otoacoustic emissions (DPOAE) tests were performed at the beginning of the study before the first drug administration and at the end of the study after the last drug administration. All rats were sacrificed, and cochleae were removed for biochemical and histopathological analysis. Results: Biochemical data indicated that paclitaxel caused oxidative stress in the cochlea. Histopathological findings revealed the loss of outer hair cells in the organ of Corti (CO) and moderate degenerative changes in the stria vascularis (SV). It was observed that DPOAE measurements were significantly reduced at high frequencies. In groups which CV was administered together with paclitaxel, these biochemical, histopathological, and functional changes were favorably reversed. Conclusion: CV may have a protective effect against paclitaxel-induced ototoxicity when given.
... Trans-anethole (14), isolated from the essential oil of N. sativa seeds by thin-layer chromatography, also showed free radical scavenging properties using several methods (Burits and Bucar, 2000). Moreover, the phenolic nature of thymol (13) and carvacrol (12) makes them to possess higher antioxidant activity than other volatile constituents in oils (see reviews by (Salehi et al., 2018;Sharifi-Rad et al., 2018;Salehi et al., 2019). In an antioxidant activity guided fractionation of the essential oil from N. sativa seeds it was found that thymoquinone 11) (51%), thymol (25%) and carvacrol (8%) were the main antioxidant compounds (Kazemi, 2015). ...
... In other cases, thymoquinone in combination with anti-cancer drugs, can exhibit antagonistic and synergistic effects (Bashmil et al., 2018). Nonetheless, as shown in "Phytoconstituents" section, Nigella genus is a rich source of phytochemicals, including dithymoquinone (10), thymohydroquinone (11), carvacrol (12), thymol (13), nigellimine-N-oxide (24), nigellicine (25), nigellidine (27), which may contribute to the anticancer properties (see reviews by Majdalawieh and Fayyad, 2016;Salehi et al., 2018;Sharifi-Rad et al., 2018;Salehi et al., 2019). Edris (2009) also remarked that β-elemene (17), which is one of the most abundant compounds in Nigella species like N. orientalis, N. damascena, and N. arvensis, has also anti-cancer properties. ...
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Nigella is a small genus of the family Ranunculaceae, which includes some popular species due to their culinary and medicinal properties, especially in Eastern Europe, Middle East, Western, and Central Asia. Therefore, this review covers the traditional uses and phytochemical composition of Nigella and, in particular, Nigella sativa. The pharmacological studies reported in vitro, in vivo, and in humans have also been reviewed. One of the main strength of the use of Nigella is that the seeds are rich in the omega-6 fatty acid linoleic acid and provide an extra-source of dietary phytochemicals, including the bioactive thymoquinone, and characteristics saponins, alkaloids, and flavonoids. Among Nigella species, N. sativa L. is the most studied plant from the genus. Due to the phytochemical composition and pharmacological properties, the seed and seed oil from this plant can be considered as good candidates to formulate functional ingredients on the basis of folklore and scientific knowledge. Nonetheless, the main limations are that more studies, especially, clinical trials are required to standardize the results, e.g. to establish active molecules, dosage, chemical profile, long-term effects and impact of cooking/incorporation into foods.
... This compound is present abundantly in the EOs of many medicinal plants and well known for its numerous biological properties, such as antimicrobial, antiviral, antioxidant, antitumor, anti-inflammatory, hepatoprotective, spasmolytic, woundhealing, and vasorelaxant activities. [23][24][25][26] Comparing the literature data, our result is in agreement with a previous study by Pino et al. 27 that showed 64% carvacrol in the EO-Pa cultivated also in Havana. Nevertheless, this component has shown wide variation in concentration. ...
... First, due to the hydrophobic character and its partition coefficient in octanol-water (log P = 3.64) it can interfere with the lipid bilayer of cytoplasmic membranes bringing loss of integrity and increasing its fluidity/permeability. 25 Then, hypotheses for mechanistic action included membrane depolarization, oxidative burst, and release of DNA, proteins, and ionmediated apoptosis. 77 On the other hand, Bakkali et al. 78 demonstrated that in eukaryotic cells, carvacrol acts as a prooxidant affecting inner cell membranes and organelles such as mitochondria. ...
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Plant-derived products are employed in various public health practices and have been considered as a major source of medicines. The genus Plectranthus (Lamiaceae) has been widely respected for its nutritional properties, its essential oil, and its therapeutic values. In the present work, the chemical characterization, antimicrobial, antiparasitic, and cytotoxic properties of the essential oil from Plectranthus amboinicus (Lour.) Spreng and its main compound carvacrol were studied. Twenty-one components were identified in the oil by gas chromatography coupled with a mass spectrometric detector. In this oil, carvacrol constitutes the major compound (71%), which represented the more abundant chemotype. The essential oil did not inhibit growth of Escherichia coli, Staphylococcus aureus, Candida albicans, Trypanosoma cruzi, or Leishmania infantum, but displayed activity against Plasmodium falciparum (half-maximal inhibitory concentration [IC 50 ] = 5.9 µg/mL), Trypanosoma brucei (IC 50 = 34.9 µg/mL), and Leishmania amazonensis (IC 50 = 58.2 µg/mL), and the human tumor-derived cell lines MCF-7 (IC 50 = 29.1 µg/mL), MDA-MB-231 (IC 50 = 41.5 µg/mL), and 22Rv1 (IC 50 = 29.6 µg/mL), but no cytotoxicity was observed against nonmalignant macrophages. The antiproliferative activity of the oil could be attributed to carvacrol. However, this compound showed certain level of cytotoxicity, which suggests unspecific activity. This study provides evidence about antimicrobial and anticancer potential of the essential oil from P. amboinicus against protozoa and neoplastic diseases, particularly as an antimalarial natural product.
... Therefore, in cookies with oregano and thyme, high content of monoterpene-carvacrol was determined. This compound, except for aroma-shaping properties, has many functional values, including antimicrobial, and anticancer [23]. Carvacrol was also characterized by high antioxidant activity [23]. ...
... This compound, except for aroma-shaping properties, has many functional values, including antimicrobial, and anticancer [23]. Carvacrol was also characterized by high antioxidant activity [23]. Furthermore, monoterpene as eucalyptol was found in cookies with rosemary. ...
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Aroma plays an important role in designing innovative functional foods. This study aimed to study the influence of incorporating herbs from the Lamiaceae family (sage, mint, rosemary, oregano, thyme) on aroma compound formation and sensory properties in oat-buckwheat products. DPPH, FRAP and PCL have been used to describe possible antioxidant activity changes and reduce power of cookies after Lamiaceae Lindl. addition. The volatiles analysis by HS-SPME-GC/MS, has shown that Lamiaceae addition significantly influences the volatiles composition (29 molecules) with a predominance of molecules with a positive sensorial impression. Cookies elaborated with herbs were characterized by a greater share of monoterpenes (e.g., limonene, eucalyptol), in the volatile profile than in control cookies. These compounds’ occurrence was closely correlated with the appearance of herbal odor and taste among sensory attributes in cookies with herbs addition. In contrast, a decrease of negative oil aroma and the bitter aftertaste was noted by a sensory panel. Moreover, in cookies of mint and rosemary, hexanal share decreased about 13 and 9.7-times, respectively. Considering all presented experiments, rosemary addition was the most effective in forming a positive aroma profile with high sensory acceptance and increased functional properties.
... Bioactive compounds from plants continue to be studied for their capacity to protect cells from damage induced by OS. Carvacrol (CV) is a phenolic monoterpenoid found in the essential oil of oregano (Origanum vulgare), thyme (Thymus vulgaris), pepperweed (Lepidium flavum), wild bergamot (Citrus aurantium bergamia) and other plants (8). CV has been reported to have a number of pharmacological properties, including antioxidant, antitumor and anti-inflammatory effects (8). ...
... Carvacrol (CV) is a phenolic monoterpenoid found in the essential oil of oregano (Origanum vulgare), thyme (Thymus vulgaris), pepperweed (Lepidium flavum), wild bergamot (Citrus aurantium bergamia) and other plants (8). CV has been reported to have a number of pharmacological properties, including antioxidant, antitumor and anti-inflammatory effects (8). To our knowledge, there is no previous research regarding the potentially protective effect of CV on retinal and/or optic nerve tissues. ...
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INTRODUCTION[|]Carvacrol (CV) is a phenolic monoterpenoid found in the essential oil of a number of aromatic plants and herbs. The present study was an investigation of the potential protective effect of CV against paclitaxel (PTX)-induced retinal and optic nerve cytotoxicity in rats.[¤]METHODS[|]A total of 18 adult male Wistar albino rats (250-400g) were randomized into 3 equal groups comprising 6 animals each. Group 1 (control group) received intraperitoneal (IP) saline solution (0.5 mL/200 g) weekly for 4 weeks. Group 2 received an IP dose of PTX (5 mg/kg), and Group 3 received CV (25 mg/kg) 30 minutes after an IP dose of PTX (5 mg/kg) weekly for 4 weeks. At the conclusion of the experimental period, the retinal and optic nerve tissues of the subjects were evaluated histopathologically. [¤]RESULTS[|]All of the retinal specimens in Group 1 (control) were histopathologically normal. In Group 2 (PTX), all of the eyes (6/6) revealed increased retinal vascularity and rosette-like structures in the outer nuclear layer, and in Group 3 (PTX-CV), all of the eyes (6/6) demonstrated normal retinal vascularity and the absence of rosette-like structures. All of the optic nerve specimens in Group 1 (control) were histopathologically normal. In Group 2 (PTX), all of the eyes (6/6) demonstrated severe vacuolization and a decreased number of astrocytes and oligodendrocytes in the optic nerve specimens, while 3 eyes (3/6) showed marked single cell necrosis. None of the eyes in Group 3 (PTX-CV) demonstrated either vacuolization or a reduction in the number of astrocytes and oligodendrocytes. No remarkable single cell necrosis was observed in the optic nerve specimens of Group 3 (PTX-CV). [¤]DISCUSSION AND CONCLUSION[|]The histopathological findings indicated that CV played a protective role against PTX-induced cytotoxicity. CV might be a promising resource to counteract oxidative stress-based cytotoxicity in the field of retinal and optic nerve disorders. [¤]
... It has been approved by the Federal Drug Administration for its uses in food (Ultee et al., 1999). Carvacrol has a different bioactivities putatively useful for clinical applications (Sharifi-Rad et al., 2018). Several studies have reported that carvacrol has different bioactivities such as antibacterial (Rattanachaikunsopon & Phumkhachorn, 2010;Ravishankar et al., 2010;Rivas et al., 2010), antifungal (Chami et al., 2004), antiviral (Pilau et al., 2011), immune modülatör (Hashemipour et al., 2013) as well as antioxidant properties (Alma et al., 2003;Radonic & Milos, 2003). ...
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Diabetes mellitus, which causes many complications, also adversely affects reproductive system in men. Studies reported that natural antioxidants are effective in reducing important complication risks caused by diabetes. Carvacrol is an antioxidant phenolic monoterpene compound with therapeutic effect in various diseases found in essential oils of aromatic plants such as pepper, wild bergamot and thyme. We aimed to investigate the effects of carvacrol on diabetes‐induced reproductive damage in male rats by evaluating the Nrf2/HO‐1 pathway and Nf‐kB‐mediated apoptosis/inflammation and spermatological parameters. For this purpose, 74 Wistar albino male rats were used. The diabetes model was performed using single‐dose intraperitoneal injection of streptozotocin 55 mg/kg. Rats were fed with carvacrol 75 mg/kg/daily/gavage for 4 and 8 weeks. Rats were divided into four groups: control group, diabetic group, carvacrol group which fed with carvacrol and the diabetic group which fed with carvacrol. It was determined that carvacrol significantly decreased malondialdehyde levels, Bax,COX‐2,Nf‐kB protein expression levels, Bax/Bcl‐2 ratio and significantly increased glutathione peroxidase, catalase activities, Bcl‐2, Nrf2,HO‐1 protein expression levels and it was determined that had a positive effect on spermatological parameters. In conclusion, the negative effects of diabetes in the male reproductive system can be prevented and/or reduced by giving carvacrol.
... There are only a few previous reports that present an in-depth overview of this important field of research. Many of the preceding publications focus exclusively on the compilation of the various pharmacological activities of the secondary metabolite carvacrol for study on natural products (Mohammad et al. 2017;Sharifi-Rad et al. 2018;Bayir et al. 2019). This review looks at the pharmacology of carvacrol, and its analogs concerning their significant potential anticancer and antimicrobial functionality to become a clinical drug. ...
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Carvacrol (cymophenol) has been reported to be the major component of aromatic plant essential oils belonging to the Labiatae family, such as Origanum vulgare and Thymus vulgaris. It is a phenolic moiety containing monoterpenoid compound, chemically known as 5-isopropyl-2-methyl phenol. Carvacrol is used in food products both as a flavoring component and as preservative. Current research is being directed to establish a potent compound carvacrol with diverse pharmacological activities, such as antioxidant, antifungal, antimicrobial, anti-inflammatory, anticancer, hepatoprotective, anti-spasmodic, anti-parasitic, and insecticidal activities. There are various derivatives of carvacrol, which possess antimicrobial action against microbial pathogens. The carvacrol phenolic group does have a good antimicrobial and anti-oxidative function. Its hydrophobic nature is owing to the existence of benzene ring and methyl and isopropyl substituents helped the moiety to bind with guanine present in DNA. This review is based upon an evaluation of the existing data or knowledge regarding the extraction of carvacrol, chemical composition of the potent derivatives synthesized from carvacrol, their pharmacological and toxicological effects. This chapter documents the above-mentioned activities and strived to critically assess the molecular pathway involved in the action of carvacrol.
... The EO antibacterial activity observed in our study may be explained by the presence of high levels of several bioactive constituents. The oxygenated monoterpene carvacrol is known to exhibit a high antimicrobial activity due to the presence in its chemical structure of the free hydroxyl group characterized by hydrophobic properties (Sellam et al. 2013;Sharifi-Rad et al. 2018). In addition, camphor present in various plants has been shown to be a powerful antimicrobial agent affecting the microbial growth by destabilizing the phospholipid bilayer structure, and acting as a proton exchanger reducing the pH gradient across the membrane (Magiatis et al. 2002;Xu 2005;Soro et al. 2014). ...
Article
The aim of this study was to determine the chemical profile of the essential oils (EOs) of three Moroccan lavender species (Lavandula pedunculata, LP; Lavandula angustifolia, LA; and Lavandula maroccana, LM) and to investigate, for the first time, the synergistic effect of the optimal mixture of the EOs with conventional antibiotic ciprofloxacin against three pathogenic foodborne bacteria. Gas chromatography/mass spectrometry analysis showed that eucalyptol (39.05%), camphor (24.21%) and borneol (8.29%) were the dominant compounds of LA‐EO. LP‐EO was characterized by the abundance of camphor (74.51%) and fenchone (27.06%), whereas carvacrol (42.08%), camphor (17.95%) and fenchone (12.05%) were the main constituents of LM‐EO. EOs alone or combined showed a remarkable antimicrobial activity against the tested bacteria with minimum inhibitory concentrations (MICs) ranging from 3.53 mg/mL to 15.96 mg/mL. The optimal mixture, calculated using a mixture design, corresponded to 19% LA, 38% LP and 43% LM. All combination of the EOs and the best EO mixture with ciprofloxacin exhibited a total synergism with fractional inhibitory concentration index (FICI) values ranging from 0.27 to 0.37. The best EO mixture showed the highest gain of 128 fold, especially against Salmonella spp., more than that found testing the EOs separately. These findings should be taken into consideration for a possible application in the pharmaceutical and food industries.
... natural products, is higher than that of the other volatile compounds due to the free hydroxyl group, hydrophobicity, and the phenol moiety. In particular, it shows a great activity against Gram-food-borne pathogens [37]. ...
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Among the top five human infections requiring medical treatment is dermatitis. Treatment of bacterial and fungal skin infections is usually based on antibiotic therapy, which is often ineffective due to the involvement of antibiotic-resistant microbial strains. The aim of this study was to compare the antimicrobial activity of essential oils (EOs) and hydrolates (Hys) extracted from six aromatic plants grown in Italy (Lavandula angustifolia, Lavandula intermedia, Origanum hirtum, Satureja montana, Monarda didyma, and Monarda fistulosa) towards fungal (Candida albicans, Candida parapsilosis, Candida glabrata and Candida tropicalis; Trichophyton soudanense, Trichophyton tonsurans, Trichophyton rubrum, Trichophyton violaceum and Microsporum canis) and bacterial strains (Staphylococcus aureus MRSA, Staphylococcus aureus MSSA, Streptococcus pyogenes, E. faecalis, Enterococcus faecalis VRE, and Enterococcus faecium) potentially pathogenic for human skin. The composition and antimicrobial activity of EOs and Hys were evaluated using the Gas-chromatography mass spectrometry and micro dilution-broth test, respectively. The volatiles’ conversion factors (CFs) were calculated to compare the activity of Hys with that of the corresponding EOs. Data show that, although the minimum inhibitory concentration values of EOs are lower than the corresponding Hys, the volatiles contained in Hys are more effective at inhibiting microbial growth because they are active at lower concentrations.
... Carvacrol presents antioxidant, antimicrobial, and antiparasitic properties, as well as anti-inflammatory, antinociceptive, hepatoprotective, anticancer, pain management activity 20,21 . Due to these properties, carvacrol is used in the food industry, the beverage industry, and perfumery [20][21][22] demonstrated that the quality of S. hortensis essential oil is increasing OPEN ...
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Saturejahortensis is one of the representative plants from the Lamiaceae family, and its essential oil has been used in various applicative fields, from the food industry to aromatherapy. The changes that occur in heated samples at different temperatures (160, 175, 190 ºC) over different periods (0.5 and 2.5 h) in Saturejahortensis essential oil composition and chemical properties were evaluated. The results showed that the major chemical composition constituents of the investigated essential oil are γ-terpinene + α-terpinolene and carvacrol + p-cymene and the thermal behavior is dependent on the content. This composition drastically changes through the heating of the samples and causes significant changes in thermal behavior. The present study demonstrated that the concentration of carvacrol in S.hortensis essential oil is increasing after heating treatment, and the sample heated at 190 ºC for 2.5 h contained more than 91% carvacrol. This simple treatment is a rapid way to obtain carvacrol from the essential oil that has high potential as a natural preservative suitable for the food industry and alternative and complementary medicine.
... Origanum vulgare, Thymus vulgaris, Lepidium flavum, Citrus aurantium bergamia are the main sources of carvacrol (De Vincenzi et al. 2004;Friedman 2014;Ziyatdinova and Budnikov 2018a). Like another isopropylmethylphenol thymol, carvacrol has shown an antimicrobial, antioxidant, and anticancer activities that can provide positive health effect (Sharifi-Rad et al. 2018). These properties of carvacrol allowed its application as a natural food preservative and flavoring additive. ...
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Glassy carbon electrode (GCE) modified with multi-walled carbon nanotubes (MWNTs) dispersed in anionic surfactant sodium dodecylsulfate (MWNTs/GCE) has been developed for the carvacrol quantification. The electrode modification provides electrocatalytic effect to carvacrol oxidation (the cathodic shift of the oxidation potential on 121 mV and 1.7-fold increase of the oxidation currents vs. GCE). The electrodes are characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The 8.4-fold higher effective surface area has been obtained for the modified electrode (75 ± 2 mm2 for MWNTs/GCE vs. 8.9 ± 0.2 mm2 for GCE). EIS data have shown 6-fold lower charge transfer resistance in comparison to GCE. The irreversible diffusion-controlled oxidation of carvacrol with participation of one electron and one proton has been proved. The parameters of electrooxidation have been calculated. Differential pulse voltammetric quantification in phosphate buffer pH 6.5 can be performed in the ranges of 0.1–25 and 25–150 μM of carvacrol. The detection limit of 0.075 μM has been achieved. The method developed has been successfully applied for the determination of total isopropylmethylphenols in oregano spices. The results obtained have been compared to independent spectrophotometric method data. Graphical abstract
... Literature data about carvacrol bioactivity, one of the most abundant phenolic monoterpenoids of oregano (as also documented in the present research by GC-MS analysis, see Table 2), would support this hypothesis. Indeed, several published works showed that this compound induces apoptosis in different tumor cell lines by increasing the ROS amount and disrupting mitochondrial membrane potential [95][96][97]. ...
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Plant secondary metabolites possess chemopreventive and antineoplastic properties, but the lack of information about their exact mechanism of action in mammalian cells hinders the translation of these compounds in suitable therapies. In light of this, firstly, Origanum vulgare L. hydroalcoholic extract was chemically characterized by spectrophotometric and chromatographic analyses; then, the molecular bases underlying its antitumor activity on B16-F10 and A375 melanoma cells were investigated. Oregano extract induced oxidative stress and inhibited melanogenesis and tumor cell proliferation, triggering programmed cell death pathways (both apoptosis and necroptosis) through mitochondria and DNA damage. By contrast, oregano extract was safe on healthy tissues, revealing no cytotoxicity and mutagenicity on C2C12 myoblasts, considered as non-tumor proliferating cell model system, and on Salmonella strains, by the Ames test. All these data provide scientific evidence about the potential application of this food plant as an anticancer agent in in vivo studies and clinical trials.
... Carvacrol is a phenolic monoterpenoid found in essential oils of O. vulgare, T. vulgaris, and other plants. A recent review showed that carvacrol has antioxidants, antimicrobial, and anti-inflammatory activity [53]. The mechanism of action of TVH, OVEO is most likely due to antioxidant capacity and anti-inflammatory activity, which are dependent on their active chemical ingredients, particularly thymol, carvacrol, epicatechin galatte, and ferulic acid. ...
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Aim: The study investigated the chemical composition, antioxidant content, and antioxidant activity of Thymus vulgaris honey (TVH) and Origanum vulgare essential oil (OVEO) and their mixture effect on carbon tetrachloride (CCl4)-induced toxicity. Materials and methods: The study conducted physicochemical characterization and chemical analysis of TVH and OVEO with the use of gas chromatography-mass spectrometry and high-performance liquid chromatograph (HPLC). The antioxidant activity of TVH and OVEO was done with the use of 1,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The study used nine groups of rats to investigate the effect of TVH, OVEO, and a mixture of TVH and OVEO (HEM) on CCl4-induced toxicity. Intraperitoneal injection of CCl4 (1 mL/100 g) was used to induce toxicity. The doses of TVH and OVEO were 1 mg/kg.b.wt, and 50 mg/kg.b.wt, respectively. HEM contains TVH (1 mg/kg.b.wt) and OVEO (50 mg/kg.b.wt). Results: TVH has a high content of phenols, flavonoids, and flavanols. HPLC analysis showed that TVH contains, for the 1st time, epicatechin gallate, and at a high concentration. OVEO includes a high percentage of carvacrol and thymol. With the use of DPPH, OVEO was more potent than TVH. CCl4 caused significant liver and kidney damage and lipid disorders, which were alleviated by HVT, OVEO, and HEM. HVT was more potent than OVEO (p<0.05), and HEM was more potent than HVT and OVEO (p<0.05). Conclusion: The study identified high content of epicatechin gallate for the 1st time in TVH, and OVEO contains a high percentage of thymol and carvacrol. Epicatechin gallate might be useful as a marker for TVH. Mixing OVEO and TVH significantly potentiated their protection against CCl4-induced liver and kidney toxicity.
... Another potential bioactive functional compound is carvacrol (CV, 5-isopropyl-2-methylphenol), a phenolic compound found primarily in oils of oregano, thyme, and marjoram, and recognized as a safe food additive (Generally Recognized as Safe-GRAS) [7,[29][30][31][32][33][34][35][36]. This bioactive compound possesses antimicrobial properties, antioxidant, and a particular aroma which makes an attractive ingredient for certain types of foods [37,38]. Moreover, CV has been also reported to be used for modification of biopolymer [5,30,31,36,[39][40][41][42][43][44], and synthethic films [45,46]. ...
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Preparation of biodegradable packaging materials and valorisation of food industry residues to achieve “zero waste” goals is still a major challenge. Herein, biopolymer-based (carboxymethyl cellulose—CMC) bioactive films were prepared by the addition, alone or in combination, of carvacrol and fungal melanin isolated from champignon mushroom (Agaricus bisporus) agro-industrial residues. The mechanical, optical, thermal, water vapour, and UV-Vis barrier properties were studied. Fourier-transform infrared (FT-IR) spectroscopy studies were carried out to analyse the chemical composition of the resulting films. Antibacterial, antifungal, and antioxidant activities were also determined. Both CMC/melanin and CMC/melanin/carvacrol films showed some antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans. The addition of melanin increased the UV-blocking, mechanical, water vapour barrier, and antioxidant properties without substantially reducing the transparency of the films. The addition of carvacrol caused loss of transparency, however, composite CMC/melanin/carvacrol films showed excellent antioxidant activity and enhanced mechanical strength. The developed bioactive biopolymer films have a good potential to be green bioactive alternatives to plastic films in food packaging applications.
... The ratio of thymol/carvacrol varies according to the oregano plant's geographical location [225]. Both compounds are lipophilic, volatile, highly soluble in ethanol, and possess low densities [224,[226][227][228]. Other bioactive oregano phytochemicals include o-cymene (2-Isopropyltoluene), apigenin (4′,5,7-trihydroxyflavone), and luteolin (7,3',4',5-tetrahydroxyflavone) [229,230] [232]. ...
Preprint
Phytonutrients are plant foods that contain many natural bioactive compounds, called phytochemicals, which expose specific biological activities. These phytonutrients and their phytochemicals may play an important role in health care maintaining normal organism functions (as preventives) and fighting against diseases (as therapeutics). Phytonutrient’s components are the primary metabolites (i.e., proteins, carbohydrates, and lipids) and phytochemicals or secondary metabolites (i.e., phenolics, alkaloids, organosulfides, and terpenes). For years, several phytonutrients and their phytochemicals have demonstrated specific pharmacological and therapeutic effects in human health such as anticancer, antioxidant, antiviral, anti-inflammatory, antibacterial, antifungal, and immune response. This review summarizes the effects of the most studied or the most popular phytonutrients (i.e., turmeric, garlic, cinnamon, graviola, and oregano), and any contraindication found. This article also calculated the physicochemical properties of the main phytochemicals in the selected phytonutrients using Lipinski’s, Veber’s and Ghose’s rules. Based on our revisions for this article, all these phytonutrients have consistently shown several in vitro, in vivo, and clinical studies with great potential as preventives and therapeutics on many diseases.
... Carvacrol is reported to have a wide variety of biological properties including antimicrobial activity. In this context, two reviews on the most relevant aspect of these activities were previously reported [86,87]. Compared to other volatile compounds present in essential oils, carvacrol shows higher antimicrobial power, due to the phenol ring, which confers hydrophobicity, and the presence of the free hydroxyl group. ...
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The vegetal world constitutes the main factory of chemical products, in particular secondary metabolites like phenols, phenolic acids, terpenoids, and alkaloids. Many of these compounds are small molecules with antibacterial activity, although very few are actually in the market as antibiotics for clinical practice or as food preservers. The path from the detection of antibacterial activity in a plant extract to the practical application of the active(s) compound(s) is long, and goes through their identification, purification, in vitro and in vivo analysis of their biological and pharmacological properties, and validation in clinical trials. This review presents an update of the main contributions published on the subject, focusing on the compounds that showed activity against multidrug-resistant relevant bacterial human pathogens, paying attention to their mechanisms of action and synergism with classical antibiotics.
... In animal models, intraperitoneal fluorouracil injection and administration of octreotide, cytokines, and antioxidant agents are under evaluation. Carvacrol exhibits anti-inflammatory and antioxidant properties, and may thus prevent stenosis caused by ingestion of caustics [12]. ...
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Introduction: We investigated the therapeutic effects of carvacrol in an experimental esophageal burn rat model with immunohistochemical techniques. Materials and Methods: Three groups were included in this study, composed of eight Wistar albino rats each. The control group was given 1 mL 0.9% (wt/vol) NaCl; esophageal burns were induced in groups 2 and 3 by administration of 1 mL 40% NaOH in the distal 2 cm of the esophagus. The treatment group was administered 75 mg/kg carvacrol in 2 mL 0.9% NaCl for 10 days. After a routine histological examination of the tissues, sections were stained with vascular endothelial growth factor (VEGF) and caspase-3 for immunohistochemical analysis and were examined under a light microscope.
... From the GC-MS study, two phenol compounds, phytol and carvacrol were signified as the important chemical constituents of T. linearis which reported to have potential anti-oomycetes activities against Rhizoctonia solani, Fusarium oxysporum and Pythium aphanidermatum (Omidbeygi et al., 2007;Mostafa et al., 2012). Phytol and carvacrol are popular in phytotherapy research for their potential antimicrobial activities and used as a dietary additive to improve animal health (Islam et al., 2018;Sharifi-Rad et al., 2018). Morever, Tampieri et al. (2003) evaluated 18 essential oils, the most effective essential oils compounds carvacrol and p cymene showed inhibitory at concentrations of 50 and 100 μg ml − 1 against S. parasitica, respectively. ...
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The present investigation estimated the potential anti-oomycetes activity of Thymus linearis leaf extract and identified the phytochemical compounds by Gas chromatography-Mass spectrometry (GC-MS). Saprolegnia parasitica isolated from the golden mahseer, Tor putitora was used for efficacy study. The effect of T. linearis plant extract on hyphal growth, zoospore production was employed by a agar diffusion method and microwell plate, respectively. The ethanolic extract of T. linearis exhibited hyphal growth inhibition to 54.45 ± 0.9% at 0.32 mg ml−1 and complete inhibition (100%) at 5.12 mg ml−1. The zoospore production was ultimately arrested at 0.32 mg ml−1 against S. parasitica. A total of 18 volatile constituents were identified from the GC–MS of the whole plant extract. The major volatile constituents in the extracts were ethyl (9z, 12z)-9, 12-octadecadienoate (22.58%), palmitic acid (11.95%), ethyl palmitate (9.89%), phytol (5.03%), stigmast-5-En-3-Ol, (3.Beta.)- (4.54%), (Z, Z)-6, 9-Cis-3, 4-epoxy-nonadecadiene (3.60%), carvacrol (3.59%), cryptomeridiol (3.22%), Heptadecanoic acid, ethyl ester (2.03%) and naphthalene, decahydro-(1.28%). Molecular docking was performed by Auto Dock Vina 4.0 of the constituents for obtaining the binding mode predictions with target proteins of S. parasitica. Phytol and carvacrol were identified to interact with plasma membrane ATPase, host target protein-1 and TKL protein kinase and V-type protein ATPase. Molecular interaction of phytol was stronger to V-type protein ATPase. From the results, it is evident that T. linearis contain various natural compounds and is recommended plant of phytopharmaceutical importance. T. linearis extract could be explored as antioomycetes compounds for treating oomycetes infections, saprolegniasis in aquaculture.
... bergamia Loisel.) and other plants. Carvacrol exhibits broad-spectrum bioactivity that may be useful in pharmacology, such as antimicrobial, antioxidant and anticancer activities [14,57,58]. Recently, the anticancer properties of CV have been described in preclinical models of breast, liver and lung carcinomas as acting on proapoptotic processes. ...
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Terpenes—a diverse group of secondary metabolites—constitute the largest class of natural products abundant in almost every plant species. The properties of concrete terpenes and essential oils have been intensively studied due to their widespread use in the pharmaceutical, food and cosmetics industries. Despite the popularity of these aromatic compounds, their derivatives, terpenoids, are still not comprehensively characterized despite exhibiting potent bioactive properties. This review aims to assess the anticancer properties of selected monoterpenes including carvone, carvacrol, perillyl alcohol, perillaldehyde, limonene, menthol and their derivatives while also evaluating potential applications as novel anticancer treatments. Special attention is paid to functional groups that improve the bioactivity of monoterpene molecules. This review also covers the therapeutic potential of deep eutectic solvents that contain monoterpene substances. Taken together, the literature supports the use of monoterpene derivatives in the development of new alternatives for disease treatment and prevention.
... Thymol, carvacrol and p-cymene are the related predominant aromatic monoterpenes of the studied M. fistulosa herb possessing the proven antimicrobial, anti-inflammatory, and antioxidant properties (42)(43)(44)(45) . Thymoquinone is also a valuable terpenoid of the Monarda species with anticancer, neuroprotective and antidiabetic activities (13,(46)(47)(48) . ...
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Two different methods of chromatographic analysis have been used in this study for the phytochemical evaluation of main secondary metabolites in the aerial part of bee balm (Monarda fistulosa L.) as the non-officinal medicinal plant of the Lamiaceae Martinov family. The high performance thin layer chromatography (HPTLC) fingerprinting method was developed for the qualitative analyses of phenolic and non-polar compounds in the bee balm herb after its maceration in the solvents of different polarity. Such polyphenols as rosmarinic, caffeic and chlorogenic acids were authentically identified in the methanol extract of herb using HPTLC. Aromatic monoterpenoid thymol was identified by the HPTLC method in the extracts obtained with non-polar solvents (toluene, methylene chloride, and chloroform). 38 volatile compounds were determined in the methylene chloride extract of M. fistulosa herb by gas chromatography mass spectrometry (GC/MS); it was taken into account only components with the content more than 0.2 %. The GC/MS analysis showed that thymol (23.73 %), followed by carvacrol (10.09 %), p-cymene (9.74 %), and thymoquinone (8.52 %) were the major constituent of methylene chloride extract. Used chromatographic techniques may be recommended for the reliable phytochemical authentication of the M. fistulosa herb.
... It must be mentioned that carvacrol possesses various pharmacological properties, especially in the treatment of cardiovascular diseases and state-of-the-art studies on its antimicrobial, antioxidant, and anticancer properties were recently reviewed [111,112]. In this context were mentioned (`) the anticancer properties in preclinical models of breast, liver, and lung carcinomas, where is acting on proapoptotic processes, (``) the effectiveness against food-borne pathogens as for example Escherichia coli, Salmonella, and Bacillus cereus, (```) the high antioxidant activity especially when it is associated with thymol. ...
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The article reviews the possibilities of encapsulating essential oils EOs, due to their multiple benefits, controlled release, and in order to protect them from environmental conditions. Thus, we present the natural polymers and the synthetic macromolecular chains that are commonly used as networks for embedding EOs, owing to their biodegradability and biocompatibility, interdependent encapsulation methods, and potential applicability of bioactive blend structures. The possibilities of using artificial intelligence to evaluate the bioactivity of EOs—in direct correlation with their chemical constitutions and structures, in order to avoid complex laboratory analyses, to save money and time, and to enhance the final consistency of the products—are also presented.
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Phenolic compounds carvacrol, thymol, eugenol and vanillin are four of the most thoroughly investigated essential oil components given their relevant biological properties. These compounds are generally considered safe for consumption and have been used in a wide range of food and non-food applications. Significant biological properties, including antimicrobial, antioxidant, analgesic, anti-inflammatory, anti-mutagenic or anti-carcinogenic activity, have been described for these components. They are versatile molecules with wide-ranging potential applications whose use may substantially increase in forthcoming years. However, some in vitro and in vivo studies, and several case reports, have indicated that carvacrol, thymol and eugenol may have potential toxicological effects. Oxidative stress has been described as a main mechanism underlying their cytotoxic behavior, and mutagenic and genotoxic effects have been occasionally observed. In vivo studies show adverse effects after acute and prolonged carvacrol and thymol exposure in mice, rats and rabbits, and eugenol has caused pulmonary and renal damage in exposed frogs. In humans, exposure to these three compounds may cause different adverse reactions, including skin irritation, inflammation, ulcer formation, dermatitis or slow healing. Toxicological vanillin effects have been less reported, although reduced cell viability after exposure to high concentrations has been described. In this context, the possible risks deriving from increased exposure to these components for human health and the environment should be thoroughly revised.
Article
OBJECTIVE: The purpose of this paper is to investigate the effect of Origanum vulgare extract as a plant with high anti-oxidant components on the induction of cell death in the Molt-4 cell line. BACKGROUND: Acute lymphocytic leukemia is characterized by the accumulation of a large number of lymphoblastic cells with high oxidant levels. METHODS: MTT assay was performed to determine the effect of O.vulgare extract on Molt-4 cells viability and the amount of 50%inhibitory concentration (IC50) was calculated. Changes in the expression of BAX and BCL-2 genes as involved in apoptosis and Nrf2 gene as a transcription factor of anti-oxidant genes in O.vulgare extract-treated Molt-4 cells were measured with Real-Time PCR. Treated Molt-4 cells were used to determine the stages of early and late apoptosis, and necrosis using acridine orange/ethidium bromide double staining. RESULTS: The results suggest survival inhibition and induction of apoptosis in Molt-4 cells treated with O.vulgare extract. Against Bax and Nrf2 genes expression, the expression of Bcl-2 gene has been reduced in Molt-4 cells following1/5 IC50 concentration of O. vulgare extract treatment. CONCLUSION: Given the oxidant drugs used in ALL treatment, and increased levels of oxidative stress in leukemic cells, induction of apoptosis by an anti-oxidant plant extract seems to be a promising way in leukemia treatment.
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Carvacrol is an essential oil traditionally used in culinary processes as spice due to its aromatic nature and also known for various biological activities. In the present study, the antivirulence efficacy of carvacrol against methicillin-resistant Staphylococcus aureus (MRSA) is explored. MRSA is an opportunistic pathogen capable of causing various superficial and systemic infections in humans. Biofilm formation and virulence factors of MRSA are responsible for its pathogenesis and resistance. Hence, the aim of this study was to explore the antibiofilm and antivirulence efficacy of carvacrol against MRSA. Carvacrol at 75 μg/mL inhibited MRSA biofilm by 93%, and it also decreased the biofilm formation on polystyrene and glass surfaces. Further, microscopic analyses revealed the reduction in microcolony formation and collapsed structure of biofilm upon carvacrol treatment. The growth curve analysis and the Alamar blue assay showed the nonfatal effect of carvacrol on MRSA. Further, carvacrol significantly reduced the production of MRSA biofilm-associated slime and extracellular polysaccharide. In addition, carvacrol strongly inhibited the antioxidant pigment staphyloxanthin and its intermediates' synthesis in MRSA. Inhibition of biofilm and staphyloxanthin by carvacrol enhanced the susceptibility of MRSA to oxidants and healthy human blood. Quantitative polymerase chain reaction (qPCR) analysis unveiled the downregulation of sarA-mediated biofilm gene expression and staphyloxanthin-associated crtM gene expression. The sarA-dependent antibiofilm potential of carvacrol was validated using S. aureus Newman wild-type and isogenic ΔsarA strains. In silico molecular docking analysis showed the high binding efficacy of carvacrol with staphylococcal accessory regulator A (SarA) and 4,4′-diapophytoene synthase (CrtM) when compared to positive controls. Furthermore, the in vivo efficacy of carvacrol against MRSA infection was demonstrated using the model organism Galleria mellonella. The results revealed the nontoxic nature of carvacrol to the larvae and the rescuing potential of carvacrol against MRSA infection. Finally, the current study reveals the potential of carvacrol in inhibiting the biofilm formation and staphyloxanthin synthesis of MRSA by targeting the global regulator SarA and a novel antivirulence target CrtM.
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Carvacrol has strong antibacterial and antiinflammatory effects and has been increasingly employed in the food and pharmaceutical industries. However, carvacrol is volatile, easily oxidized, and difficult to dissolve in water. In this study, carvacrol was encapsulated with mixed cyclodextrins during enzymatic cyclodextrin synthesis and microencapsulated carvacrol was obtained by spray drying. The encapsulation efficiency and encapsulation yield of microencapsulated carvacrol were 92.16% and 72.30%, respectively. The encapsulation yield for the pure β-cyclodextrin/carvacrol inclusion complex (38.96%) was lower than that of microencapsulated carvacrol (50.44%) when the guest/host ratio was 1:4. No significant difference (P > 0.05) in the amount of encapsulated carvacrol was found when the guest/host ratio was less than 1:6. Microencapsulated carvacrol appeared in scanning electron micrographs as spherical particles with obvious invaginations. Determination of the inclusion formation constant, NMR analysis, and molecular modeling revealed that cavity size affected the ability of cyclodextrins to include carvacrol. Finally, the rate constants (k) of carvacrol release from microencapsulated carvacrol (1.09‒8.53×10⁻⁴) at various temperatures and relative humidities were systematically lower than those of β-cyclodextrin/carvacrol inclusion complexes (5.20‒199×10⁻⁴). This study transcended traditional essential oil-cyclodextrin inclusion formation by developing a mixed-cyclodextrin inclusion compound that achieved better encapsulation and superior release.
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Nowadays, almost 300 essential oils (EOs) are commonly traded in the world market, with a prediction to be worth over $14 billion in 2024. EOs are natural preservatives for food products in order to reduce the activity of pathogenic microorganisms, therefore their use as an antioxidant or a preservative in foods has been encouraged. They are not only considered as antimicrobial or flavoring agents, but are also incorporated into food packaging materials. There are several types of EOs which have been approved as food additives by the Food and Drug Administration. Hence, it is important to use safe EO products to minimize possible adverse effect risks such as nausea, vomiting, necrosis, nephropathy, mucous membrane, and skin irritation. This review article gives information about some EOs that are used in the food industries and the types of some allergenic compounds and biocides which could make the EOs hazardous or may cause allergenic reactions in the human body. Besides, some analysis techniques of possible allergenic compounds or biocides in EOs were introduced and supported with the most relevant studies. The overall conclusion from the study is that pregnant women, patients taking drugs (e.g., diabetics) or the having a history of allergy are the most prone to be affected from EO allergenic components. As regards to biocides, organochlorine and organophosphorus types of pesticides that are carried over from the plant may be found mostly in EOs. The most common allergic reaction is skin sensitization and irritation if the EO components are oxidized during storage or transportation. Moreover, drug interactions are one of the other possible adverse effect. Hence, determination of biocides and possible allergenic component concentrations is an essential factor when they are used as a preservative or flavoring agent. The most prominent analysis techniques are gas and liquid chromatography because most of the allergens and biocides are mainly composed of volatile components. Practical Application Determining of the essential oil's content will be crucial if oils are used for food preservation or flavoring because they may have some hazardous effects, such as nausea, vomiting, necrosis and nephropathy. Therefore, after applying them to the food products, consumers (especially pregnant women) should be informed about their concentration levels and their possible adverse effects are taken into account when they are consumed over toxic limit. For this reason, we reviewed in our study that some allergenic components, biocides and toxic limits of EOs to be used in food products. In addition to this, recent analytical techniques have been explained and discussed which methods are suitable for analysis.
Article
The present study evaluated the effect of yogurt-based marinade combined with active essential oil components (EOs) namely: thymol (TH), carvacrol (CA), and cinnamaldehyde (CI) on Listeria monocytogenes, Escherichia coli O157:H7 and Salmonella spp. in camel meat (CM) chunks during storage at 4 and 10 °C. Fresh cocktail mixtures of L. monocytogenes, E. coli O157:H7 and Salmonella spp. strains were inoculated on CM samples. Subsequently, a yogurt-based marinade, with or without 1% or 2% of the added EOs, was mixed with the CM chunks. After treatment, marinated camel samples were stored at 4 and 10 °C for 0, 1, 4 and 7 days. Adding yogurt-based marinade to the CM samples did not cause any significant changes in L. monocytogenes, E. coli O157:H7 and Salmonella spp. numbers at 4 °C, but at 10 °C resulted in a significant decrease in numbers on day 4 and 7 of storage by 1.4-1.5; 2.7-2.1 and 2.5-2.8 log CFU/g, respectively, compared to untreated CM samples. The incorporation of EOs into the CM with marination (CMM) further enhanced the microbial reduction of E. coli O157:H7 and Salmonella. At 10 °C, the synergistic effect of EOs with marinade was greater than at 4 °C. Increasing the concentration of the EOs used in this study from 1% to 2%, enhanced E. coli O157:H7 and Salmonella spp. reduction during storage at 4 and 10 °C while L. monocytogenes numbers were not affected. Increasing active EO component concentrations to 2% caused further significant reductions in Salmonella spp. in the CMM samples during storage by 1.0-2.7 log CFU/g (P ˂ 0.05) at 4 and 10 °C. At 10 °C, increasing the concentration of CI and TH to 2% caused a further reduction (P ˂ 0.05) of E. coli O157:H7 numbers by days 4 and 7 in the range of 3.6-4.4 log CFU/g. Among all tested EOs, 2% TH and 2% CI had the greatest effect against E. coli O157:H7 and Salmonella spp. in CMM during storage at 4 and 10 °C. In comparison to CMM, the highest scores of all examined sensory attributes were found in CMM samples with 1% and 2% CI added. Results indicate that the EO component CI can be used as an effective tool to decrease populations of E. coli O157:H7 and Salmonella spp. in CM with minor sensory changes.
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Por estar relacionado com as maiores Taxas de Mortalidade (TM) em todo mundo, o câncer representa um dos maiores problemas de saúde pública da atualidade. O presente estudo propõe-se a analisar a distribuição dos cânceres com as maiores TM feminina nas regiões brasileiras e o comportamento do câncer de maior impacto. Para tanto, foi realizada uma pesquisa documental no Atlas de Mortalidade Online do Instituto Nacional de Câncer (INCA), considerando os 5 tipos de cânceres com as maiores TM em mulheres no período de 2001-2015. Conhecendo-se o câncer de maior magnitude, foi analisada sua distribuição segundo as regiões de ocorrência e por faixa etária. Assim, os cânceres de mama, brônquios e pulmões, colo do útero, estômago e cólon demostraram as maiores TM no Brasil, sendo o câncer de mama o de maior magnitude. Em algumas regiões, surgiram situações distantes do padrão nacional, como a permanência do câncer de colo de útero na posição de segunda maior TM e o aparecimento dos cânceres de encéfalo e fígado e vias biliares intra-hepáticas entre os 5 de maior mortalidade. O câncer de mama, que possui a maior TM, aumenta seus índices medida que as faixas etárias aumentam. Conclui-se que os cânceres de mama, brônquios e pulmões, colo do útero, estômago e cólon descrevem o cenário de morbimortalidade brasileiro caracterizando um país em desenvolvimento.
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Most of approximately 1.8 billion people involved in agriculture protect their food products using pesticides especially insecticides which may remain in foods as pesticide residues. Among insecticides organophosphates such as malathion have been widely used around the world and others such as parathion has been restricted because of their toxicity. Carvacrol (CAR) is the main component of Satureja khuzestanica. Since chemical composition of foods can alter toxicity of pesticides, in this work, the effect of coadministration of CAR and organophosphates on renal function has been studied and compared with the effect of coadministration of carvacrol loaded beta cyclodextrin-alginate-chitosan (BAC) based nanoflowers. Serum levels of urea and creatinine and histological examination were analyzed after 10 days of administration of chemicals. Malathion and parathion significantly increased urea and creatinine and induced renal inflammation. However, coadministration of CAR or BAC-CAR modified urea and creatinine and improved renal inflammation. BAC-CAR modified serum levels of urea more efficient than CAR (P < 0.05). It is concluded that BAC could be considered as a carrier for drugs used to treat renal disorders. Carvacrol can be used in the formulation of organophosphate pesticides, which may control pests more efficiently than conventional organophosphate pesticides.
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Plant volatile organic compounds (volatiles) are secondary plant metabolites that play crucial roles in the reproduction, defence, and interactions with other vegetation. They have been shown to exhibit a broad range of biological properties and have been investigated for antimicrobial and anticancer activities. In addition, they are thought be more environmentally friendly than many other synthetic chemicals 1. Despite these facts, their applications in the medical, food, and agricultural fields are considerably restricted due to their volatilities, instabilities, and aqueous insolubilities. Nanoparticle encapsulation of plant volatile organic compounds is regarded as one of the best strategies that could lead to the enhancement of the bioavailability and biological activity of the volatile compounds by overcoming their physical limitations and promoting their controlled release and cellular absorption. In this review, we will discuss the biosynthesis and analysis of plant volatile organic compounds, their biological activities, and limitations. Furthermore, different types of nanoparticle platforms used to encapsulate the volatiles and the biological efficacies of nanoencapsulated volatile organic compounds will be covered.
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A taxa de mortalidade é um índice demográfico que expressa o número de mortes registradas de uma determinada região em um período de tempo. Pode ser considerada como um forte indicador social, uma vez que, quanto pior as condições de vida, maior será a taxa de mortalidade. O objetivo desta pesquisa é traçar o perfil dos óbitos infantis que ocorreram na última década (2006-2016), com enfoque no estado da Paraíba. Trata-se de uma pesquisa exploratória do tipo documental com abordagem qualitativa. Os dados foram obtidos durante setembro e outubro de 2018, através da plataforma eletrônica do Departamento de Informática do SUS (DATASUS). Apesar da redução importante da taxa de mortalidade infantil (TMI) no Brasil, um número expressivo de mortes infantis ainda faz parte da realidade social do País. Tais mortes, em sua maioria, ocorrem por causas evitáveis, principalmente no que diz respeito às ações dos serviços de saúde. Ao longo de 10 anos a Paraíba permaneceu relativamente estável no que diz respeito a redução da TMI, o que chama atenção para a efetividade das políticas públicas de promoção à saúde materno-infantil. Com relação ao perfil dos óbitos infantis da Paraíba, a prematuridade, via de parto vaginal, sexo masculino e baixo peso ao nascer caracterizam as maiores TMI. Esses fatores compilam para a iminente necessidade de revisão e aprimoramento das políticas públicas voltadas à qualidade da assistência à saúde materno-infantil na Paraíba.
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The effect of carvacrol (CAR) on oxidative stress, inflammation, and liver dysfunction induced by lipopolysaccharide (LPS) was explored. The rats (n=40) were daily injected (2 weeks) by saline as control, LPS (1 mg/kg, i.p.), and 25, 50 or 100 mg/kg CAR (i.p.) before LPS. LPS increased aspartate transaminase (AST: 162±13 U/L), alanine aminotransferase (ALT: 74.6±2.15 U/L), alkaline phosphatase (ALK-P: 811±51 U/L), interlukine-1β (IL-1β: 1254±51 pg/g tissue), malondialdehyde (MDA: 32±1.09 nM/g tissue), and nitric oxide (NO: 224±13.5 nM/g tissue) (P<0.01–P<0.001) while, decreased total protein(4.08±0.38 g/dl), albumin(2.79±0.16 g/dl), thiol (5.16±0.19 μM/g tissue), superoxide dismutase (SOD: 10.57±0.13 U/g tissue), and catalase (CAT: 0.78±0.02 U/g tissue) compared to control (P<0.001). CAR reversed the effects of LPS (P<0.05–P<0.001). In the rats treated by 100 mg/kg CAR, the indicators were as follows: AST: 118±10.1 U/L, ALT: 42.5±4.13 U/L, ALK-P: 597±39.91 U/L, IL-1β: 494±15 pg/g tissue, and NO: 141±5.35 nM/g tissue. Both 50 and 100 mg/kg CAR corrected oxidative stress indicators and in the group treated by 100 mg/kg CAR, they were: MDA: 23.4±0.91 nM/g tissue, thiol: 7.98±0.18 μM/g tissue, SOD: 21±0.8 U/g tissue, and CAT: 1.12±0.02 U/g tissue(P<0.05–P<0.001). In conclusion, CAR improved liver function, accompanied with antioxidant and antiinflammatory effects.
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Aim Cadmium (Cd) is a toxic heavy metal that causes severe toxic effects on different tissues including liver and kidney. Therefore the research for alternatives to reduce the damage caused by Cd has substantial importance. This study was performed to examine the possible modulatory effects of carvacrol (CRV) against Cd-induced hepatorenal toxicities and the possible mechanisms underlying these effects. Materials and methods In the present study, 35 male Wistar rats were randomly divided into 5 groups. The rats were treated with Cd (25 mg/kg) and treated with CRV (25 and 50 mg/kg body weight) for 7 consecutive days. Key findings CRV could modulate Cd-induced elevations of ALT, ALP, AST, urea, creatinine, MDA and enhance antioxidant enzymes' activities such as SOD, CAT, and GPx, and GSH's level. CRV also reversed the changes in levels of inflammatory biomarker and apoptotic genes that include NF-κB, Bcl-3, MAPK-14, iNOS, COX-2, MPO, PGE2, Bax, Bcl-2, P53, Caspase-9, Caspase-6 and Caspase-3 in both tissues. The levels of 8-OHdG in the Cd-induced liver and kidney tissues were modulated after CRV treatment. Furthermore, CRV treatment considerably lowered Cd, Na, Fe, and Zn content while increased K, Ca, Mg and Cu contents in both tissues as compared to the Cd-exposed rats. Significance The results of the present study revealed that CRV supplementation could be a promising strategy to protect the liver and kidney tissues against Cd-induced oxidative damage, inflammation and apoptosis.
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Decontamination of fresh meats without negatively impact on their sensory quality is a big challenge. In this study, the single or combined effect of antimicrobials (chitosan, carvacrol, tea polyphenols) and low dose gamma irradiation (≤2 kGy) against Salmonella Typhimurium and Staphylococcus aureus on fresh pork meat were assessed. The effects of these treatments on the color and lipid oxidization of pork meat were also evaluated. Irradiation at 1 kGy reduced 2.2 logs of S. Typhimurium and 1.6 logs of S. aureus, while the treatments of 1 kGy irradiation combined with chitosan (1%)-carvacrol (0.2%) or chitosan (1%)-tea polyphenols (0.5%) achieved 3.2 log reduction of S. Typhimurium and 5.1 log reductions of S. aureus. Irradiation at 2 kGy in combination with chitosan-carvacrol obtained over 5 log reductions of S. Typhimurium and S. aureus. There was no recovery/regrowth of S. Typhimurium or S. aureus in vacuum packaged meat samples throughout the 14 d storage period. There were no significant differences among all meat samples in color (L*, a*, b* values) after 7 d, while the combined treatments increased the lightness (L*) after 14 d of storage at 4 °C. The treated meat samples had lower content of malondialdehyde, indicating less lipid oxidation in pork meat during storage. This study demonstrates that the combined low dose irradiation with these antimicrobial surface treatments is promising for improving fresh pork safety and quality.
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Aims: In the age where bacterial resistance to conventional antibiotics is increasing at an alarming rate, the use of the traditional plant, herb extracts, or other bioactive constituents is gradually becoming popular as an anti-virulence agent to treat pathogenic diseases. Carvacrol, a major essential oil fraction of Oregano possesses a wide range of bioactivities. Therefore, we aimed to study the effect of sub-inhibitory concentrations of carvacrol on major virulence traits of V. cholerae. Methods and results: We have used in vitro as well as ex vivo models to access the anti-pathogenic role of carvacrol. We found that the sub-inhibitory concentration of carvacrol significantly repressed bacterial mucin penetrating ability. Carvacrol also reduced the adherence and fluid accumulation in the rabbit ileal loop model. Reduction in virulence is associated with the downregulated expression of tcpA,ctxB,hlyA, and toxT. Furthermore, carvacrol inhibits flagellar synthesis by downregulating the expression of flrC and most of the class III genes. Conclusions: Carvacrol exhibited anti-virulence activity against V. cholerae, which involved many events including the inhibition of mucin penetration, adhesion, reduced expression of virulence-associated genes culminating in reduced fluid accumulation. Significance and impact of study: These findings indicate that carvacrol possesses inhibitory activity against V. cholerae pathogenesis and might be considered as a potential bio-active therapeutic alternative to combat cholera.
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Carvacrol has shown antimicrobial activity against a wide range of Gram-positive and Gram-negative bacteria. However, its hydrophobic nature, volatility, and susceptibility to oxidation mediated by light or heat limit its use. Nanoencapsulation provides a protective barrier against degradation and volatilization processes and improves the dispersibility of bioactive compounds. A simple, rapid, and sensitive analytical method was developed and validated by UV spectrophotometry to quantify carvacrol in a nanoemulsion obtained by self-nanoemulsification, using acetonitrile as a solvent to recover the analyte from the nanoemulsion. The UV scanning spectrum of carvacrol (240–300 nm) in acetonitrile showed maximum absorbance at wavelength 275 nm, typical of this monoterpene. The calibration curve was linear from 15 to 65 μg/ml, with a determination coefficient of 0.999. The detection and quantification limits found were 1.6455 and 4.9863 μg/ml, respectively. The validation results confirmed that the method developed is specific, linear, accurate, and precise and it can be successfully applied for the determination of encapsulation efficiency and the content of carvacrol present in a nanoemulsion.Graphical abstract
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Streptococcus pyogenes is an important human pathogen worldwide. The identification of natural antibacterial phytochemicals has renewed interest due to the current scarcity of antibiotic development. Carvacrol is a monoterpenoid found in herbs. We evaluated carvacrol alone and combined with selected antibiotics against four strains of S. pyogenes in vitro. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of carvacrol against S. pyogenes were 125 µg/mL (0.53 mM) and 250 µg/mL (1.05 mM), respectively. Kill curve results showed that carvacrol exhibits instantaneous bactericidal activity against S. pyogenes. We also demonstrated the potential mechanism of action of carvacrol through compromising the cell membrane integrity. Carvacrol induced membrane integrity changes leading to leakage of cytoplasmic content such as lactate dehydrogenase enzymes and nucleic acids. We further confirmed dose-dependent rupturing of cells and cell deaths using transmission electron microscopy. The chequerboard assay results showed that carvacrol possesses an additive-synergistic effect with clindamycin or penicillin. Carvacrol alone, combined with clindamycin or penicillin, can be used as a safe and efficacious natural health product for managing streptococcal pharyngitis.
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Aim: The inhibitory and antibiofilm effects of Thymus vulgaris (EOTv) and Hyptis spicigera essential oils (EOHs) on cariogenic microorganisms were evaluated. Materials & methods: The chemical characterization of EOTv was performed by gas chromatography/mass spectrometry. Streptococcus mutans, Streptococcus gordonii, Streptococcus sanguinis, Streptococcus mitis, Streptococcus sobrinus, Lactobacillus acidophilus and Actinomyces naeslundii were used for agar diffusion assays and determination of minimal inhibitory and minimal bactericide concentrations. In addition, 20 streptococci and lactobacilli clinical isolates were also tested. The effects of essential oil on microbial initial biofilm formation and on preformed microcosm biofilm formed from human saliva were studied. Results & conclusion: Both essential oils had inhibitory effects on the cariogenic species and reduced the bacterial adherence to dental enamel. Essential oils were able to disrupt preformed microcosm biofilms. Thymus vulgaris and Hyptis spicigera essential oils have potential to be used in the development of formulations to the control of cariogenic biofilms.
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Purpose : To investigate the modulatory effect of the natural phytochemical, carvacrol, on Topotecan (TOPO) cytotoxicity and cellular uptake in different cancer cell lines. Methods : The cytotoxicity of the carvacrol/TOPO combination therapy was determined in vitro using crystal violet assay. Coomassie blue and DAPI fluorescent stains were used for cellular morphology and molecular cell death assessments, respectively. Additionally, TOPO cellular uptake after carvacrol/TOPO combination therapy was determined. Results : Treatment of HeLa and HCT116 with carvacrol/TOPO resulted in 7.70- and 5.71-fold reduction in TOPO half maximal inhibitory concentration (IC 50 ), respectively, relative to TOPO single treatment. On the other hand, treatment of MCF-7, HepG2, SKOV3, and A549 cancer cells with carvacrol/TOPO resulted in increasing the IC 50 of TOPO by 1.49-, 1.33-, 1.50- and 1.26-fold, respectively, relative to TOPO single treatment. Conclusion : Carvacrol had enhanced TOPO cytotoxicity and cellular uptake in HeLa and HCT116 cancer cells but might cause TOPO resistance in MCF-7, HepG2, SKOV3 and A549 cells.
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There is an increasing need for novel drugs and new strategies for the therapy of invasive candidiasis. This study aimed to develop and characterize liposome-based nanoparticles of carvacrol, cinnamaldehyde, citral or thymol with anti- Candida activities. Dioctadecyldimethylammonium bromide- and monoolein-based liposomes in a 1:2 molar ratio were prepared using a lipid-film hydration method. Liposomes were assembled with equal volumes of liposomal stock dispersion and stock solutions of carvacrol, cinnamaldehyde, citral or thymol in dimethyl sulfoxide. Cytotoxicity was tested on RAW 264.7 macrophages. In vitro antifungal activity of liposomes with phytocompounds was evaluated according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology using clinical isolates of Candida albicans , Candida auris , Candida dubliniensis and Candida tropicalis . Finally, the ability of macrophage cells to kill Candida after the addition of phytocompounds and their nanoparticles was determined. Nanoparticles with 64 μg/ml of cinnamaldehyde, 256 μg/ml of citral and 128 μg/ml of thymol had the best characteristics among the formulations tested. Highest encapsulation efficiencies were achieved with citral (78 to 83%) and carvacrol (66 to 71%) liposomes. Carvacrol and thymol in liposome-based nanoparticles were non-toxic regardless of the concentration. Moreover, carvacrol and thymol maintained their antifungal activity after encapsulation and there was a significant reduction (∼ 41%) of yeast survival when macrophages were incubated with carvacrol or thymol liposomes. In conclusion, carvacrol and thymol liposomes possess high stability, low cytotoxicity, and antifungal activity that acts synergistically with macrophages.
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Introduction: The scientific research in the field of api-aromatherapy is promising and aims to develop a new generation of natural products with interesting therapeutic properties, at a time when the misuse of available pharmaceutical products makes them almost no or more effective. Aromiel, a mixture of honey and essential oil, is a product that has been the subject of few studies so far and whose synergistic power of its components well documented in the literature, makes it attractive. Objectives: This work focuses on the Aromiel and has for general objectives the determination of the phytochemical profile of the mixture and the characterization of the criteria of quality and standardization of the product. A particular interest will be brought to the antioxidant power of the mixture via a thorough pharmacological study of the synergistic combination Honey-essential oil. Methods: The natural products used concern different samples of honey from Palestine and Morocco as well as Oregano essential oil. The physicochemical parameters and the phytochemical profile of these samples were determined. Antioxidant activity was evaluated by the DPPH, FRAP and molybdate tests. In vitro investigations on the effect of Aromiel on bacterial strains as well as in vivo studies were performed on rats to evaluate the antibacterial effect and the hepato-nephroprotective effect against induced toxicity by CCl4. This effect has been compared to that of honey and essential oil studied separately. Results: The quality study revealed that the honeys and essential oils used meet standards of quality and standardization and are a potential source of bioactive molecules objectified by considerable antioxidant power. On the microbiological level, the synergistic action between honeys and the essential oil of Origanum vulgare was objectified toward multidrug-resistant bacteria: Aromiel (Vs essential oil alone) was able to reduce MICs by 4 times on Gram-positive bacteria and 8-fold on Gram-negative bacteria. In addition, it has been found that the more honey is rich in tannic acid, ferulic, gallic, epicatechin galate, and melanoidin, the more it tends to synergize with the combined essential oil. Metabolically, Aromiel has a greater hepato-nephroprotective effect against CCl4- induced damage than that of honey or essential oil used separately. The administration of the mixture of Origanum vulgare essential oil and honey of Thymus vulgaris showed a potential synergistic effect. This argues for the interaction between the polyphenols identified in the two matrices (carvacrol and thymol for the essential oil and epicatchin gallate and ferulic acid for honey). Conclusion: Our results show that Aromiel, a promising natural product, has a powerful antioxidant power related to the synergistic action of the different bioactive molecules present in the mixture.
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We present the development of surfactant‐free, silica‐free and fully biobased oil‐in‐water antimicrobial Pickering emulsions, based on the self‐assembly of b ‐cyclodextrin and phytoantimicrobial oils (terpinen‐4‐ol or carvacrol). Undecylenic acid (UA), derived from castor oil, can be used as bio‐based drug to treat fungal infection, but is less effective than petroleum‐based drugs as azole derivatives. To maximize its antifungal potential, we have incorporated UA in fully biobased Pickering emulsions. These emulsions are effective against fungi, Gram‐positive and Gram‐negative bacteria. The carvacrol emulsion charged with UA is +390 % and +165 % more potent against methicillin‐resistant S. aureus (MRSA), compared to UA and azole‐based commercial formulations. Moreover, this emulsion is up to +480 % more efficient that UA ointment against C. albicans . Finally, remarkable eradication of E. coli and MRSA biofilms was obtained with this environmental‐friendly emulsion.
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Propiconazole is a broadly used fungicide that leaves residues in food and water causing severe dangerous effects on humans and animals. The current investigation was performed to evaluate the propiconazole toxicity on the liver and kidney of male albino rats and to assess the protective role of carvacrol against these adverse effects. Sixty male Wistar albino rats were used in this experiment and were divided into four equal groups: control group, propiconazole group, carvacrol group, and propiconazole + carvacrol group. Rats were treated daily by oral gavage for 60 days with propiconazole (75 mg/kg) and/or carvacrol (50 mg/kg). The results demonstrated that exposure to propiconazole resulted in a significant elevation in serum biomarkers that indicate malfunction of the liver and kidney. Additionally, exposure to propiconazole resulted in oxidative stress and lipid peroxidation manifested by a significant reduction in glutathione content and catalase activity, and a significant increase in malondialdehyde content in the liver and kidney. These toxic effects were confirmed by histopathological studies and DNA laddering assay. Conversely, carvacrol reduced propiconazole-induced detrimental effects and improved the histopathological pictures of both liver and kidney tissues. Therefore, carvacrol can be used as a prophylactic natural compound against propiconazole-induced toxic effects in the liver and kidney.Graphical abstract
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The resistance of hospital bacterial isolates against traditional germicides, which used frequently, is one of the important factors contributing to emerging nosocomial infections. Moreover, due to having the side effects of chemical substances, the development of novel low-risk natural compounds seems necessary for control the spread of resistant pathogens in hospital environments. The aim of this study was to compare the effect of carvacrol and glutaraldehyde against two common hospital acquired pathogens, including Pseudomonas aeruginosa and Staphylococcus aureus. In this study 365 samples were collected from different wards of hospitals of Khorramabad, Iran. One hundred and sixty samples were identified as P. aeruginosa and S. aureus by using standard microbiological methods. Then the antibacterial effects of four combinations including carvacrol+ethanol, carvacrol+dimethyl sulfoxide (DMSO), glutaraldehyde 2%, and pure glutaraldehyde (50%) were evaluated and determined using dilution broth and disk diffusion methods. Our results showed that the carvacrol had more antibacterial effects against selected bacteria compared to glutaraldehyde. Moreover, the optimal time and concentration of carvacrol+ethanol against hospital isolates of P. aeruginosa and S. aureus was determined after 1 h at concentration of 64 μl/ml and 8 μl/ml, respectively. In conclusion by comparing the results of carvacrol and glutaraldehyde, seem that carvacrol, as an herbal and natural agent, may be a suitable alternative to glutaraldehyde in hospital equipment’s’ sterilization.
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Thymol and carvacrol are phenolic isomers with the potential developmental toxicity and endocrine disruptions (ED) at low concentrations. However, few reports estimated their toxicity and ED below 10⁻⁶ M (150 μg/L) (MW of thymol and carvacrol: 150 g/mol). In this study, both chemicals were determined for the developmental toxicity and potential ED at 500 μg/kg and 50 μg/kg using the chicken embryonic assay, potential estrogenic activity (EA) at 10⁻¹² to 10⁻⁷ M (1.5×10⁻⁴ to 15 μg/L) by the MCF-7 cell proliferation assay, mutagenicity at 10⁻¹² to 10⁻⁶ M (1.5×10⁻⁴ to 150 μg/L) by the Ames test, and an in silico method for ED. Carvacrol showed mutagenic risks at 10⁻⁷, 10⁻⁸, and 10⁻¹¹ M (15, 1.5, and 0.0015 μg/L) while thymol at 10⁻⁶ and 10⁻⁸ M (150 and 1.5 μg/L). Carvacrol negatively impacted embryonic growth at 50 μg/kg, with weak EA at 10⁻⁸ M (1.5 μg/L). Carvacrol but not thymol had weak EA at 10⁻¹² M (1.5×10⁻⁴ μg/L). Molecular docking to 14 types of hormone-related receptors revealed that carvacrol had higher binding affinities to two estrogen receptors and the mineralocorticoid receptor than those to thymol. Carvacrol and thymol varied in toxicities due to a different location of one phenolic hydroxyl group.
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In the present study, antibacterial efficiency of Carvacrol was studied on nine types of pathogenic bacteria isolated from different clinical samples, S. aureus, S. epidermidis, St. pneumonia, E. coli, Klebsiella pneumonia, Proteus mirabilis, Pseudomonas aeroginosa, Enterobacter spp. and Serratia spp. the inhibitory effects of this oil were compared with standard antibiotics, ciprofloxacin. The inhibition effect of Carvacrol in different concentration of bacterial growth were studied, the results showed that there is a great inhibition growth on all studied bacterial isolates except Pseudomonas aeroginosa.
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Plants of the genus Zingiber (Family Zingiberaceae) are widely used throughout the world as food and medicinal plants. They represent very popular herbal remedies in various traditional healing systems; in particular, rhizome of Zingiber spp. plants has a long history of ethnobotanical uses because of a plethora of curative properties. Antimicrobial activity of rhizome essential oil has been extensively confirmed in vitro and attributed to its chemical components, mainly consisting of monoterpene and sesquiterpene hydrocarbons such as α-zingiberene, ar-curcumene, β-bisabolene and β-sesquiphellandrene. In addition, gingerols have been identified as the major active components in the fresh rhizome, whereas shogaols, dehydrated gingerol derivatives, are the predominant pungent constituents in dried rhizome. Zingiber spp. may thus represent a promising and innovative source of natural alternatives to chemical food preservatives. This approach would meet the increasing concern of consumers aware of the potential health risks associated with the conventional antimicrobial agents in food. This narrative review aims at providing a literature overview on Zingiber spp. plants, their cultivation, traditional uses, phytochemical constituents and biological activities.
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Zataria multiflora Boiss (Z. multiflora) belongs to the Lamiaceae family, is used traditionally for culinary and medicinal purposes. Different pharmacological effects have been described for the plant including; bronchodilation, vasodilation and effect on lung inflammation. The plant is also used as a remedy against cough in the traditional medicine. In this article, "pharmacological effects of Z. multiflora and its constituents focusing on their anti-inflammatory, antioxidant and immunomodulatory properties were reviewed" by searching various databases until "June" 2016. The anti-inflammatory effects of the plant such as decreased total white blood cell (WBC), neutrophils and eosinophils counts were demonstrated. The protective effects of Z. multiflora on serum levels of phospholipase A2 (PLA2) and total protein were showed. In addition, constituents of the plant, such as flavonoids and carvacrol also showed anti-inflammatory effects. Z. multiflora also reduced oxidative stress by scavenging free radicals and can be used in the therapy of oxidative damage. Decreased level of malondialdehyde (MDA) and protective effects of Z. multiflora on serum levels of nitric oxide (NO) were also shown. Improvement of the serum levels of IgE, reduction of pro-inflammatory cytokine (IL-4, TGF-β and IL-17), and increased anti-inflammatory cytokines (IFN-γ and FOXP3), were shown for Z. multiflora and its constituents, carvacrol and thymol. These results indicated that carvacrol and thymol could be used for treatment of inflammatory diseases as new anti-inflammatory agents. Therefore, Z. multiflora showed anti-inflammatory, anti-oxidant and immunomodulatory effects which could be used for treatment of inflammatory and immune-dysregulation diseases or disorders associated with increased oxidative stress. This article is protected by copyright. All rights reserved.
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Carvacrol, thymol and eugenol belong to a class of naturally presenting phenols with a ten-carbon unit, which are present in essential oils of many plants. These versatile molecules are incorporated as useful ingredients in many food products and find applications in agricultural, pharmaceutical, fragrance, cosmetic, flavor and other industries. They are wide ranging of biological and pharmaceutical activities: anti-inflammatory, antimicrobial, analgesic, anticancer and antioxidant. This review summarizes pharmacological and medicinal activities of these phytochemicals and their synthetic hybrids. Graphical Abstract
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The potential of plant essential oils (EOs) in anticancer treatment has recently received many research efforts to overcome the development of multidrug resistance and their negative side effects. The aims of the current research are to study (i) the cytotoxic effect of the crude EO extracted from Origanum vulgare subsp hirtum and its main constituents (carvacrol, thymol, citral and limonene) on hepatocarcinoma HepG2 and healthy human renal cells HEK293; (ii) the antibacterial and phytotoxic activities of the above EO and its main constituents. Results showed that cell viability percentage of treated HepG2 by EO and its main constituents was significantly decreased when compared to untreated cells. The calculated inhibition concentration (IC50) values for HepG2 were lower than healthy renal cells, indicating the sort of selectivity of the studied substances. Citral is not potentially recommended as an anticancer therapeutic agent, since there are no significant differences between IC50 values against both tested cell lines. Results showed also that oregano EO and its main constituents have a significant antibacterial activity and a moderate phytotoxic effect. The current research verified that oregano EO and its main constituents could be potentially utilized as anticancer therapeutic agents.
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Tuberculosis is a highly infectious disease declared a global health emergency by the World Health Organization, with approximately one third of the world's population being latently infected with Mycobacterium tuberculosis. Tuberculosis treatment consists in an intensive phase and a continuation phase. Unfortunately, the appearance of multi drug-resistant tuberculosis, mainly due to low adherence to prescribed therapies or inefficient healthcare structures, requires at least 20 months of treatment with second-line, more toxic and less efficient drugs, i.e., capreomycin, kanamycin, amikacin and fluoroquinolones. Therefore, there exists an urgent need for discovery and development of new drugs to reduce the global burden of this disease, including the multi-drug-resistant tuberculosis. To this end, many plant species, as well as marine organisms and fungi have been and continue to be used in various traditional healing systems around the world to treat tuberculosis, thus representing a nearly unlimited source of active ingredients. Besides their antimycobacterial activity, natural products can be useful in adjuvant therapy to improve the efficacy of conventional antimycobacterial therapies, to decrease their adverse effects and to reverse mycobacterial multi-drug resistance due to the genetic plasticity and environmental adaptability of Mycobacterium. However, even if some natural products have still been investigated in preclinical and clinical studies, the validation of their efficacy and safety as antituberculosis agents is far from being reached, and, therefore, according to an evidence-based approach, more high-level randomized clinical trials are urgently needed.
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Nutritional strategies focused on the use of phytochemicals as modulators of immunological and physiological responses, as well as antistress and antioxidant therapies and health promoters of the gastrointestinal tract have attracted increased interest in animal production. Over the past two decades, several studies have reported positive results of using plant essential oils (EOs) as dietary additive in several farm animal species. Recently, these nutritional alternatives have been evaluated and reported in fish production in order to enhance the resistance to diseases and prevent outbreaks, as well as to improve fish growth, animal welfare and feed utilization. However, despite the diverse and relevant biological activities reported, these phytochemicals are composed of often unstable and volatile molecules, which makes the chemical and physical characteristics of the EOs important aspects to be considered in fish nutrition research. This review summarizes the current knowledge regarding the use of plant EOs as fish dietary additives, focusing on their potential as modulators of the gut bacterial community and discussing some aspects regarding their stability in feeds.
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Essential oils are complex mixtures of hydrocarbons and their oxygenated derivatives arising from two different isoprenoid pathways. Essential oils are produced by glandular trichomes and other secretory structures, specialized secretory tissues mainly diffused onto the surface of plant organs, particularly flowers and leaves, thus exerting a pivotal ecological role in plant. In addition, essential oils have been used, since ancient times, in many different traditional healing systems all over the world, because of their biological activities. Many preclinical studies have documented antimicrobial, antioxidant, anti-inflammatory and anticancer activities of essential oils in a number of cell and animal models, also elucidating their mechanism of action and pharmacological targets, though the paucity of in human studies limits the potential of essential oils as effective and safe phytotherapeutic agents. More well-designed clinical trials are needed in order to ascertain the real efficacy and safety of these plant products.
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Aim: The biopotential of the essential oils of the Greek aromatic plants Satureja thymbra and Satureja parnassica were investigated, together with their major components carvacrol, thymol, γ-terpinene and p-cymene. Materials and methods: Antioxidant and cancer cell cytotoxic properties were determined using 2,2-diphenyl-1-picrylhydrazyl and sulforhodamine B assays, respectively. The antiproliferative potential was studied against the MCF-7, A549, HepG2 and Hep3B cell lines. Results: S. thymbra oil possessed stronger antioxidant and antiproliferative capacity when tested on MCF-7 cells compared to S. parnassica oil. Thymol exhibited two-fold greater antioxidant potency than carvacrol, whereas γ-terpinene and p-cymene had no significant effect. Carvacrol was the most potent antiproliferative agent against A549 cells, while Hep3B cells were most sensitive to thymol. p-Cymene and γ-terpinene demonstrated negligible bioactivity. Conclusion: S. thymbra and S. parnassica essential oils exhibit significant but diverse antioxidant and antiproliferative activities, mainly attributed to their main components, carvacrol and thymol.
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A study was conducted to evaluate the efficacy of supplementation of carvacrol (CL), a phytochemical, in ameliorating changes in growth performance and oxidative stress induced by aflatoxin B1 in male broiler chicken fed with maize-soy based diets. The feeding trial of five week duration was conducted with 120 chicks which were divided into 5 dietary treatments with 3 replicates having 8 chicks in each following a completely randomized design. The dietary treatments consisted of: basal diet without any supplement (G1), basal diet supplemented with 1.0% CL (G2), diet contaminated with 1.0 ppm toxin (G3), diet contaminated with 1.0 ppm toxin and supplemented with 1.0% CL (G4), and diet contaminated with 1.0 ppm toxin and supplemented with 0.5% each of CL and HSCAS (G5). The growth performance and FCR of broiler chicken supplemented with CL was poor than birds fed basal diet and AFB1 contaminated feed. The weight of liver in AFB1 group of birds showed an increase while in CL supplemented groups it was comparatively low. Activity of serum enzymes ALT, AST were observed to be high and activity of the oxidative stress marker enzymes CAT, SOD and GSR low in AFB1 group birds. A reverse trend in activity of these enzymes was obtained in CL and binder supplemented groups which was not significant in case of GSR. CL supplemented group of birds recorded higher TAC, protein and glucose and lower MDA, TC and triglyceride compared to AFB1 group birds. The severity and degree of the liver lesions obtained in microscopic observation in CL supplemented birds was far less compared to livers of birds fed aflatoxin contaminated feed. It can be concluded that CL is effective in ameliorating aflatoxin induced changes with regard to oxidative stress in broiler chickens but had no positive impact on growth performance.
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Plants belonging to the genus Allium are widely cultivated and used all over the world as food and medicinal plants. Since ancient times, these plants, particularly garlic (Allium sativum L.) and onion (Allium cepa L.), have represented important components of typical recipes and traditional healing systems. Not the least of which, their use as food biopreservatives is well documented, due to the relevant antibacterial activity of their extracts and essential oils. In addition to garlic and onion, this review article deals with the main members of the genus Allium, including A. ampeloprasum (Leek), A. schoenoprasum (Chive) and A. ascalonicum (Shallot), focusing both on their ethnonutritional uses and potential as promising food biopreservative agents. Noteworthy, recent research has demonstrated Allium derivatives to be novel components in active edible coatings as well as nanoformulates.
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Biofilms are complex communities of microorganisms, responsible for more than 60% of the chronic human infections and they represent one of the leading concerns in medicine. Pseudomonas aeruginosa is human pathogenic bacteria which causes numerous diseases and is known for its ability to produce biofilm. Ocimum basilicum L. (basil) and Salvia officinalis L. (sage) are widely used plants in traditional medicine for the treatment of different conditions. Therefore, the aim of this study was to investigate the potential of basil and sage essential oils against P. aeruginosa biofilm producing strains. The efficacy of two essential oils on P. aeruginosa biofilm forming ability was determined using crystal violet method. Out of 15 strains isolated from different clinical biological samples, two were strong, 11 moderate and one weak biofilm producer. Good efficacy of sage essential oil towards strong and weak biofilm producers, but not of basil essential oil, was observed. In the case of moderate biofilm producers, 81.8% showed lower biofilm production after incubation with the sage oil, while 63.6% showed the reduction of biofilm production after basil essential oil treatment. The obtained results showed high potential of both oils for the treatment of persistent infections caused by Pseudomonas aeruginosa biofilms.
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Essential oils and organic acids are used as feed additives to improve health status and reduce colonization with pathogens. Although bactericidal in vitro, concentrations achieved in the animal gut are probably not lethal to pathogens. The aim of this study was to investigate the effects of cinnamaldehyde, carvacrol and cinnamic, lactic and propionic acids on the ability of Salmonella typhimurium ATCC 14028 (ST) to invade intestinal epithelial cells (IPEC-J2) and on the expression levels of immune related genes in the cells. The minimum inhibitory concentration (MIC) and non-inhibitory concentration (NIC) were determined and influence on the invasion capacity of ST was investigated. The structure of fimbriae and flagella was analysed by electron microscopy, and expression levels of HSP70, IkBa, IL-8 and IL-10 in the IPEC-J2 cells were carried out by q-PCR. Cinnamaldehyde, carvacrol and cinnamic and propionic acids inhibited ST invasion but not cell viability, bacterial viability and motility or the development of flagella. Propionic acid and cinnamaldehyde in combination with cinnamic acid caused structural impairment of fimbriae. Cinnamaldehyde up-regulated expression of HSP70 irrespective of the presence of organic acids or ST; exposure to carvacrol induced HSP70 only in the presence of propionic acid and ST.
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Recent studies indicate that intestinal oxidative stress and microbiota imbalance is involved in weaning-induced intestinal dysfunction in piglets. We have investigated the effect of feeding a carvacrol-thymol blend supplemented diet on intestinal redox status, selected microbial populations and the intestinal barrier in weaning piglets. The piglets (weaned at 21 days of age) were randomly allocated to two groups with six pens per treatment and 10 piglets per pen. At weaning day (21 days of age), six piglets were sacrificed before weaning to serve as the preweaning group. The weaned group was fed with a basal diet, while the weaned-CB group was fed with the basal diet supplemented with 100 mg/kg carvacrol-thymol (1 : 1) blend for 14 days. On day 7 post-weaning, six piglets from each group were sacrificed to determine intestinal redox status, selected microbial populations, messenger RNA (mRNA) transcript levels of proinflammatory cytokines and biomarkers of intestinal barrier function. Weaning resulted in intestinal oxidative stress, indicated by the increased concentration of reactive oxygen species and thiobarbituric acid-reactive substances present in the intestine. Weaning also reduced the population of Lactobacillus genus and increased the populations of Enterococcus genus and Escherichia coli in the jejunum, and increased mRNA levels of tumor necrosis factor α (TNF-α), interleukin 1β and interleukin 6 (IL-6). In addition, decreased mRNA levels of zonula occludens and occludin in the jejunal mucosa and increased plasma diamine oxidase concentrations indicated that weaning induced dysfunction of the intestinal barrier. On day 7 post-weaning, supplementation with the carvacrol-thymol blend restored weaning-induced intestinal oxidative stress. Compared with the weaned group, the weaned-CB group had an increased population of Lactobacillus genus but reduced populations of Enterococcus genus and E. coli in the jejunum and decreased mRNA levels of TNF-α. The results indicated that weaning induced intestinal oxidative stress and dysfunction of the intestinal barrier. Dietary supplementation with 100 mg/kg carvacrol-thymol (1 : 1) decreased the intestinal oxidative stress and influenced selected microbial populations without changing the biomarkers of intestinal barrier in weaning piglets.
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Oregano is a perennial shrub that grows in the mountains of the Mediterranean and Euro/Irano-Siberian regions. This study was conducted to identify the major constituents of the ethanolic Origanum vulgare extract and examine the cytotoxic, antioxidant, and antibacterial properties of the extract but more importantly the contribution of its specific major constituent(s) or their combination to the overall extract biological activity. Gas chromatography/mass spectroscopy analysis showed that the extract contained monoterpene hydrocarbons and phenolic compounds, the major ones being carvacrol and thymol and to a lesser extent p-cymene, 1-octacosanol, creosol, and phytol. A549 epithelial cells challenged with the extract showed a concentration-dependent increase in cytotoxicity. A combination of thymol and carvacrol at equimolar concentrations to those present in the extract was less cytotoxic. The A549 cells pretreated with nonlethal extract concentrations protected against hydrogen-peroxide-induced cytotoxicity, an antioxidant effect more effective than the combination of equimolar concentrations of thymol/carvacrol. Inclusion of p-cymene and/or 1-octacosanol did not alter the synergistic antioxidant effects of the carvacrol/thymol mixture. The extract also exhibited antimicrobial properties against Gram-positive and Gram-negative bacterial strains including clinical isolates. In conclusion, the oregano extract has cytotoxic, antioxidant, and antibacterial activities mostly attributed to carvacrol and thymol.
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Restraint stress may be associated with elevated free radicals, and thus, chronic exposure to oxidative stress may cause tissue damage. Several studies have reported that carvacrol (CAR) has a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CAR on restraint stress induced oxidative stress damage in the brain, liver, and kidney. For chronic restraint stress, rats were kept in the restrainers for 6 h every day, for 21 consecutive days. The animals received systemic administrations of CAR daily for 21 days. To evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) activities were measured in the brain, liver, and kidney. In the stressed animals that received vehicle, the MDA level was significantly higher ( P < 0.001 ) and the levels of GSH and antioxidant enzymes were significantly lower than the nonstressed animals ( P < 0.001 ). CAR ameliorated the changes in the stressed animals as compared with the control group ( P < 0.001 ). This study indicates that CAR can prevent restraint stress induced oxidative damage.
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Background: Nowadays more than half of the populations in the world are suffering from dandruff. Malassezia fungus is an important factor in causing dandruff as it may stimulate cytokine production by keratinocytes (epidermal cells that synthesize keratin) and inflammatory pathways. As dandruff is a hurting issue for people, a lot of efforts are being done for treatment. Many reports based on medicinal plants, seem to be more effective in curing mentioned concern. Objectives: The aim of this research was to investigate a clinical trial for dandruff therapy by Zinc L-pyrrolidone carboxylic acid (Zinc-PCA) and pirocton olamine in combination with six medicinal plant extracts. Patients and Methods: In this study, the combination of Punica granatum L, Rosmarinus officinalis L, Matricaria chamomilla L, Urtica dioica L, Mentha piperita L., and Salvia officinalis L. methanolic extracts with Pirocton Olamine and Zinc-PCA in the shampoo form were tested on 30 patients with dandruff on hair within a period of two months. Chronic dandruff of 15 patients were highly removed in the second week, 12 other patients suffering from dandruff were seen with dandruff removal after 28 days, while remaining sufferers expressed satisfaction at the end of the fifth week. Results: Based on the results, medicinal plant extracts have marvelous effects on dandruff removal with fewer side effects, though it takes long time to treat the mentioned concern. Conclusions: The results show that applying the combination of medicinal plant extracts and natural ingredients with chemical compounds in pharmaceutical industry can optimize treatment.
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Aflatoxins (AF) are toxic metabolites primarily produced by molds, Aspergillus flavus and As-pergillus parasiticus. Contamination of poultry feed with AF is a major concern to the poultry industry due to severe economic losses stemming from poor performance , reduced egg production, and diminished egg hatchability. This study investigated the inhibitory effect of 2 generally regarded as safe (GRAS), natural plant compounds, namely carvacrol (CR) and trans-cinnamaldehyde (TC), on A. flavus and A. parasiticus growth and AF production in potato dextrose broth (PDB) and in poultry feed. In broth culture, PDB supplemented with CR (0%, 0.02%, 0.04% and 0.08%) or TC (0%, 0.005%, 0.01% and 0.02%) was inoculated with A. flavus or A. parasiticus (6 log CFU/mL), and mold counts and AF production were determined on days 0, 1, 3, and 5. Similarly, 200 g portions of poultry feed supplemented with CR or TC (0%, 0.4%, 0.8%, and 1.0%) were inoculated with each mold, and their counts and AF concentrations in the feed were determined at 0, 1, 2, 3, 4, 8, and 12 weeks of storage. Moreover, the effect of CR and TC on the expression of AF synthesis genes in A. flavus and A. parasiticus (aflC, nor1, norA, and ver1) was determined using real-time quantitative PCR (RT-qPCR). All experiments had duplicate samples and were replicated 3 times. Results indicated that CR and TC reduced A. flavus and A. parasiticus growth and AF production in broth culture and chicken feed (P < 0.05). All tested concentrations of CR and TC decreased AF production in broth culture and chicken feed by at least 60% when compared to controls (P < 0.05). In addition, CR and TC down-regulated the expression of major genes associated with AF synthesis in the molds (P < 0.05). Results suggest the potential use of CR and TC as feed additives to control AF contamination in poultry feed.
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Aflatoxins (AF) are toxic metabolites primarily produced by molds, Aspergillus flavus and Aspergillus parasiticus. Contamination of poultry feed with AF is a major concern to the poultry industry due to severe economic losses stemming from poor performance, reduced egg production, and diminished egg hatchability. This study investigated the inhibitory effect of 2 generally regarded as safe (GRAS), natural plant compounds, namely carvacrol (CR) and trans-cinnamaldehyde (TC), on A. flavus and A. parasiticus growth and AF production in potato dextrose broth (PDB) and in poultry feed. In broth culture, PDB supplemented with CR (0%, 0.02%, 0.04% and 0.08%) or TC (0%, 0.005%, 0.01% and 0.02%) was inoculated with A. flavus or A. parasiticus (6 log CFU/mL), and mold counts and AF production were determined on days 0, 1, 3, and 5. Similarly, 200 g portions of poultry feed supplemented with CR or TC (0%, 0.4%, 0.8%, and 1.0%) were inoculated with each mold, and their counts and AF concentrations in the feed were determined at 0, 1, 2, 3, 4, 8, and 12 weeks of storage. Moreover, the effect of CR and TC on the expression of AF synthesis genes in A. flavus and A. parasiticus (aflC, nor1, norA, and ver1) was determined using real-time quantitative PCR (RT-qPCR). All experiments had duplicate samples and were replicated 3 times. Results indicated that CR and TC reduced A. flavus and A. parasiticus growth and AF production in broth culture and chicken feed (P < 0.05). All tested concentrations of CR and TC decreased AF production in broth culture and chicken feed by at least 60% when compared to controls (P < 0.05). In addition, CR and TC down-regulated the expression of major genes associated with AF synthesis in the molds (P < 0.05). Results suggest the potential use of CR and TC as feed additives to control AF contamination in poultry feed.
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Microorganisms within a biofilm have a distinct phenotype from planktonic cells and generally show higher tolerance to antimicrobial agents. Due to these properties of biofilm-associated cells there is a great interest to finding substances, which inhibit specific processes in the initial phase of biofilm formation and therefore prevent the formation of mature biofilms. Hence, the purpose of this study was to examine the influence of thymol and carvacrol on the planktonic population, initial adhesion and preformed C. albicans biofilms, in vitro. Results for antifungal activity of essential oil components (EOC’s) against planctonic population of C. albicans were identical for both tested EOC’s (MIC/MFC=0.156/0.3125 μL/mL). In order to understand the anti-biofilm action of EOC’s, their effect was tested on both the initial cell attachment by planktonic cells as well as on preformed biofilms. Obtained results indicated that the effect of EOC’s on initial cell attachment was dosage dependent manner, although even at 1×MIC biomass attachment was reduced by 61.3 % for thymol and 58.9 % for carvacrol. Using 2×MIC, biomass attachment was reduced for 81.7 % for thymol and 80.9 % for carvacrol. When the same EOC’s were tested against a preformed biofilm, their inhibitory effect was reduced greatly.
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Chlorhexidine (CHX), one of the most effective drugs administered for periodontal treatment, presents collateral effects including toxicity when used for prolonged periods; here, we have evaluated the bactericidal potency and the cytocompatibility of Juniperus excelsa M. Bieb essential oil (EO) in comparison with 0.05% CHX. The EO was extracted from berries by hydrodistillation and components identified by gas chromatography and mass spectrometry. Bacterial inhibition halo analysis, quantitative cell viability 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino) carbonyl]-2H-tetrazolium hydroxide assay (XTT), and colony forming unit (CFU) count were evaluated against the two biofilm formers Aggregatibacter actinomycetemcomitans and Streptococcus mutans. Finally, cytocompatibility was assessed with human primary gingival fibroblasts (HGF) and mucosal keratinocytes (HK). The resulting EO was mainly composed of monoterpene hydrocarbons and oxygenated monoterpenes. An inhibition halo test demonstrated that both bacteria were sensitive to the EO; XTT analysis and CFU counts confirmed that 10-fold-diluted EO determined a statistically significant (p < 0.05) reduction in bacteria count and viability towards both biofilm and planktonic forms in a comparable manner to those obtained with CHX. Moreover, EO displayed higher cytocompatibility than CHX (p < 0.05). In conclusion, EO exhibited bactericidal activity similar to CHX, but a superior cytocompatibility, making it a promising antiseptic alternative to CHX.
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Objective: The increasing prevalence of antibiotic-resistant bacterial infections led to identify alternative strategies for a novel therapeutic approach. In this study, we synthesized ten carvacrol codrugs - obtained linking the carvacrol hydroxyl group to the carboxyl moiety of sulphur-containing amino acids via an ester bond - to develop novel compounds with improved antimicrobial and antibiofilm activities and reduced toxicity respect to carvacrol alone. Method: All carvacrol codrugs were screened against a representative panel of Gram positive (S. aureus and S. epidermidis), Gram negative (E. coli and P. aeruginosa) bacterial strains and C. albicans, using broth microdilution assays. Findings: Results showed that carvacrol codrug 4 possesses the most notable enhancement in the anti-bacterial activity displaying MIC and MBC values equal to 2.5 mg/mL for all bacterial strains, except for P. aeruginosa ATCC 9027 (MIC and MBC values equal to 5 mg/mL and 10 mg/mL, respectively). All carvacrol codrugs 1-10 revealed good antifungal activity against C. albicans ATCC 10231. The cytotoxicity assay showed that the novel carvacrol codrugs did not produce human blood hemolysis at their MIC values except for codrugs 8 and 9. In particular, deepened experiments performed on carvacrol codrug 4 showed an interesting antimicrobial effect on the mature biofilm produced by E. coli ATCC 8739, respect to the carvacrol alone. The antimicrobial effects of carvacrol codrug 4 were also analyzed by TEM evidencing morphological modifications in S. aureus, E. coli, and C. albicans. Conclusion: The current study presents an insight into the use of codrug strategy for developing carvacrol derivatives with antibacterial and antibiofilm potentials, and reduced cytotoxicity.
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The genus Echinacea consists of 11 taxa of herbaceous and perennial flowering plants. In particular, Echinacea purpurea (L.) Moench is widely cultivated all over the United States, Canada, and in Europe, exclusively in Germany, for its beauty and reported medicinal properties. Echinacea extracts have been used traditionally as wound healing to improve the immune system and to treat respiratory symptoms caused by bacterial infections. Echinacea extracts have demonstrated antioxidant and antimicrobial activities, and to be safe. This survey aims at reviewing the medicinal properties of Echinacea species, their cultivation, chemical composition, and the potential uses of these plants as antioxidant and antibacterial agents in foods and in a clinical context. Moreover, the factors affecting the chemical composition of Echinacea spp. are also covered.
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Thymol is a naturally occurring phenol monoterpene derivative of cymene and isomer of carvacrol. Thymol (10–64%) is one of the major constituent of essential oils of thyme (Thymus vulgaris L., Lamiaceae), a medicinal plant with several therapeutic properties. This plant, native to Mediterranean regions, is commonly used as a culinary herb and also with a long history of use for different medicinal purposes. Nowadays, thymol and thyme present a wide range of functional possibilities in pharmacy, food, and cosmetic industry. The interest in the formulation of pharmaceuticals, nutraceuticals, and cosmeceuticals based on thymol is due to several studies that have evaluated the potential therapeutic uses of this compound for the treatment of disorders affecting the respiratory, nervous, and cardiovascular systems. Moreover, this compound also exhibits antimicrobial, antioxidant, anticarcinogenesis, antiinflammatory, and antispasmodic activities, as well as a potential as a growth enhancer and immunomodulator. In the present review, these bioactivities have been covered because some of them can contribute to explain the ethnopharmacology of thymol and its main source, T. vulgaris. Other important aspects about thymol are discussed: its toxicity and bioavailability, metabolism, and distribution in animals and humans.
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Cancer is a multifactorial disease, and therefore, a multitarget approach is needed to face the complex cancer biology, based on the combined use of different natural and synthetic anticancer agents able to target synergistically multiple signaling pathways involved in carcinogenesis, including angiogenesis and metastasis. In this view, the plant kingdom represents an unlimited source of phytotherapeutics with promising perspectives in the field of anticancer drug discovery. This narrative review aims to provide an updated overview on the bioactive phytochemicals exhibiting a promising potential as adjuvants in conventional anticancer therapies, with emphasis on antiangiogenic and antimetastatic activities.
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Programmed cell death (PCD) is probably the most widely discussed subject among the topics of cancer therapy. Over the last 2 decades an astonishing boost in our perception of cell death has been seen, and its role in cancer and cancer therapy has been thoroughly investigated. A number of discoveries have clarified the molecular mechanism of PCD, thus expounding the link between PCD and therapeutic tools. Even though PCD is assumed to play a major role in anticancer therapy, the clinical relevance of its induction remains uncertain. Since PCD involves multiple death programs including programmed necrosis and autophagic cell death, it has contributed to our better understanding of cancer pathogenesis and therapeutics. In this review, we discuss a brief outline of PCD types as well as their role in cancer therapeutics. Since irregularities in the cell death process are frequently found in various cancers, key proteins governing cell death type could be used as therapeutic targets for a wide range of cancer.
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Nepeta schiraziana Boiss. (Lamiaceae) is a species endemic of Iran used in traditional medicine to treat a number of ailments. This study investigates the chemical composition as well as the cytotoxic, antimicrobial, acetylcholinesterase (AChE) inhibitory and antioxidant activities of N. schiraziana essential oil (EO). EO chemical composition was analysed by GC-MS. Cytotoxicity was evaluated against MCF-7 and Hep-G2 cancer cells, while antimicrobial activity was assessed against fungi (Candida albicans, Aspergillus niger), Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gramnegative (Klebsiella pneumonia, Pseudomonas aeruginosa) bacteria. Forty-four compounds were identified; the main constituents were 1,8-cineole (33.67%), germacrene D (11.45%), β-caryophyllene (9.88%), caryophyllene oxide (7.34%). N. schiraziana EO showed a concentration-dependent cytotoxicity against both cancer cell lines. It also significantly inhibited the growth of A. niger (MIC 1.85 ± 1.12) and C. albicans (MIC 4.94 ± 3.07 μg/mL). MIC for S. aureus, B. subtilis, K. pneumoniae and P. aeruginosa were 16.37 ± 1.23, 168.22 ± 2.14, 180.99 ± 4.67 and 248.74 ± 5.12 μg/mL, respectively. Slight antiradical and AChE inhibitory activities were measured. This is the first report on the chemical composition and bioactivities of N. schiraziana EO. The antibacterial, antifungal and anticancer properties were confirmed in vitro. © 2017, Romanian Society for Pharmaceutical Sciences. All rights reserved.
The genus Eremurus is native to Eastern Europe and temperate Asia. Particularly, Eremurus persicus (Joub. & Spach) Boiss. is highly valued in traditional foods and medicine. Scientific knowledge about E. persicus chemical composition and bioactivity is required. Therefore, the present study is aimed to determine the volatile composition of E. persicus essential oil (EO) by means of gas chromatography coupled to flame ionization/mass spectrometry detection. Moreover , the antioxidant, antimicrobial, anticancer, and acetylcholinesterase inhibitory activities of the EO were tested. Interestingly, the anti-dermatophyte potency was close to that of the drug griseofulvin, with minimum fungicidal concentration ranging between 0.7 and 4.5% depending on the fungi strain. The EO was also effective against hepatocellular carcinoma (Hep-G2) and breast adenocarcinoma (MCF-7) human cancer cell lines in a concentration (200-1500 ng/mL)-dependent manner, with a decrease of the cell viability up to 65% and 52%, respectively. The E. persicus EO was rich in terpenes and oxygenated terpene derivatives. Individually , limonene (16.25%), geranylgeraniol (15.23%), n-nonanal (9.48%), geranyl acetone (9.12%), benzene acetaldehyde (8.51%), linalool (7.93%), α-pinene (6.89%), and 1,8-cineol (5.22%) were the most abundant volatile compounds and could be chosen as analytical markers of this essential oil. In conclusion, our results suggested that this EO possesses a wide range of bioactive properties that could be useful in nutraceutical, functional foods and cosmeceutical formulations.
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Carvacrol, a major monoterpenoid phenol from Origanum and Thymus species, has been shown to exhibit antiproliferative and anticancer properties in a few recent studies. Nevertheless, detailed mechanism of the action of this compound in prostate cancer has not been elucidated yet. Therefore, in the current study, we examined the anticancer activity and mechanism of the action of carvacrol against human prostate cancer cells. It was found that the treatment of DU145 cells with carvacrol decreased cell viability in a concentration and time-dependent manner. The antiproliferative action of carvacrol leads to induction of apoptosis as confirmed by nuclear condensation, Annexin V-FITC/PI positive cells, and caspase-3 activation. In addition, carvacrol augmented reactive oxygen species generation and disruption in the mitochondrial membrane potential which has not been reported in the previous studies of carvacrol with prostate cancer. Moreover, carvacrol-induced apoptosis of prostate cancer cells was also accompanied by significant amount of growth arrest at the G0/G1 phase of the cell cycle which has also not been documented previously. To sum up, this study has established that carvacrol could be a promising chemotherapeutic agent and could have a direct practical implication and translational relevance to prostate cancer patients as Origanum consumption may retard prostate cancer progression.
In recent years, with increased the prevalence of viral infections and having no specific for their treatment and also the continuous appearance of resistant viral strains, the finding of novel antiviral agents is necessary. In this study, monoterpenes of thymol, carvacrol, p-cymene and essential oils from Sinapis arvensis L., Lallemantia royleana Benth. and Pulicaria vulgaris Gaertn. were screened for their inhibitory effect against herpes simplex virus type 1 (HSV-1) in vitro on Vero cell line CCL-81-ATCC using a plaque reduction assay. The antiviral activity of three monoterpenes (thymol, carvacrol and p-cymene) and three essential oils were evaluated by cytotoxicity assay, direct plaque test. In addition, the modes of antiviral action of these compounds were investigated during the viral infection cycle. Results showed that the inhibitory concentrations (IC50) were determined at 0.002%, 0.037%, >0.1%, 0.035%, 0.018% and 0.001% for thymol, carvacrol, p-cymene, S. arvensis oil, L. royleana oil and P. vulgaris oil, respectively. A manifestly dose-dependent virucidal activity against HSV-1 could be exhibited for compounds tested. In order to determine the mode of the inhibitory effect, compounds were added at different stages during the viral infection cycle. At maximum noncytotoxic concentrations of the compounds, plaque formation was significantly reduced by more than 80% when HSV-1 was preincubated with p-cymene. However, no inhibitory effect could be observed when the compounds were added to the cells prior to infection with HSV-1 or after the adsorption period. Conclusion: These results indicate that compounds affected HSV-1 mostly before adsorption and might interact with the viral envelope. Thymol exhibited a high selectivity index and seems to be a promising candidate for topical therapeutic application as antiviral agent for treatment of herpetic infections.
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The aim of this study was to evaluate concentration-dependent antioxidant and anticancer activities of CA and RA in ethanol extracts of three different Oregano species (Origanum onites L., Origanum vulgare L. and Origanum vulgare ssp. hirtum). The study revealed the highest RA antioxidant activity in O. vulgare ssp. hirtum (9550± 95 mmol/g) and the lowest in O. vulgare L. (2605± 52 mmol/g) (p<0.05). The highest CA amount was present in O. onites L., which was 1.8 and 4.7 times higher (p<0.05) than in O. vulgare ssp. hirtum and O.vulgare L., respectively. The anticancer activity was evaluated on human glioblastoma (U87) and triple negative breast cancer (MDA-MB231) cell lines in vitro. RA anticancer activity was negligible. CA and the extracts were about 1.5 2 times more active against MDA-MB231 cell line (p<0.05) compared to U87 cell line. The anticancer activities of three tested extracts were similar against U87 cell line (p>0.05) but they had different activities against MDA-MB231 cell line.
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Plants belonging to Melaleuca genus (Myrtaceae family) are native to Oceania, where they have been used for ages by Aborigine people in Australian traditional medicine, mainly because of their broad-spectrum antimicrobial activity. Although, M. linariifolia, M. dissitiflora, and other species of Melaleuca can also be used, the tea tree oil, an essential oil obtained from M. alternifolia shows the longest history of medicinal uses. Tea tree oil contains for the 80–90% several monoterpenes (terpinen-4-ol, α-terpinene, 1,8-cineol, p-cymene, α-terpineol, α-pinene, terpinolene, limonene, and sabinene). Sesquiterpenes and aromatic compounds further compose this oil. The essential oil of Melaleuca spp. has been reported to possess effective antibacterial and antifungal properties in vitro. In particular, data show that 1,8-cineol, terpinen-4-ol and methyl eugenol play the key role in mediating this oil’s antimicrobial activity.