Behavioral and electrophysiological responses of the male medfly, Ceratitis capitata, to thymol and carvacrol ethers.

BACKGROUND: The Mediterranean fruit fly, Ceratitis capitata, is one of the most economically important insect pests attacking fruits and vegetables in tropical and subtropical areas of the world. Semiochemical-based pest management programs are being used to provide environmentally friendly control methods for medflies. The goals of the current study were to discover potential new, attractive, kairomones by designing, synthesizing, and testing simplified ethers of thymol and carvacrol along with their ether derivatives in short-range attraction assays and electroantennogram (EAG) assays with male C. capitata. To the best of our knowledge, this study represents the first investigation of thymol and carvacrol, and their respective ethers for attractancy to C. capitata, a major agricultural pest worldwide. RESULTS: In short-range attraction bioassays, parent compounds, thymol and carvacrol, along with their propyl, butyl, benzyl, and octyl ethers captured the most male C. capitata. The attraction patterns changed over time and captures were only significant if they were greater than the positive control tea tree oil (TTO) at 90 min. In EAG assays, thymol benzyl, octyl ethers, and carvacrol benzyl ether evoked significantly greater antennal responses than their parent compounds. The EAG responses did not correlate with short-range male attraction. The aliphatic side chains of thymol and carvacrol had a small effect on the activity. Future studies will investigate the long-range attraction of the ethers that elicited large EAG responses. CONCLUSION: This report provides new information for discovering potential kairomones through synthesis and structure-activity studies for sterile male medflies. Thymol, carvacrol, and several of their ether derivatives displayed improved longevity of attraction compared with TTO (a strong medfly attractant), with significantly higher captures than TTO observed at 90 min in laboratory bioassays. Further chemical synthesis of thymol and carvacrol ethers within this series may lead to the development of ethers that are more attractive or persistent than their parent compounds, thymol and carvacrol. © 2024 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Carvacrol ameliorates skin allograft rejection through modulating macrophage polarization by activating the Wnt signalling pathway.

Post-transplantation immune rejection remains an important factor for transplant patients. However, conventional immunosuppressants are associated with substantial adverse effects. Natural immunosuppressants present a promising alternative to conventional counterparts, boasting exceptional biological activity, minimal toxicity and reduced side effects. We identified carvacrol as a prospective immunosuppressive agent following T cell proliferation experiment and validated carvacrol's immunosuppressive efficacy in the murine allogeneic skin graft model. T cell proliferation assay was used to screen natural small molecule compounds and the immunosuppressive effect of compounds was evaluated in MHC-mismatched murine allogeneic skin graft model. H&E and immunohistochemical staining were applied to evaluate the pathological grade. Furthermore, flow cytometry was uitlized to analyse the immunophenotype changes of immune cells. Western blotting and q-PCR were used to detect the expression of key molecules in macrophages. In vitro, carvacrol demonstrates significant inhibition of the proliferation of CD4+ T and CD8+ T cells. It notably reduces inflammatory factor expression within the allografts, suppresses T cell differentiation toward Th1 phenotype and expansion. Furthermore, carvacrol prominently hinders M1-type macrophages polarization by activating Wnt signaling. Notably, the anti-rejection efficacy of carvacrol was significantly weakened upon the removal of macrophages in mice using chlorophosphate liposomes. Carvacrol could significantly inhibit T cell proliferation, alleviate graft rejection and has outstanding toxicological safety. The molecular mechanism of the anti-rejection effect of carvacrol is closely related to its mediating activation of macrophage Wnt pathway, inhibiting M1 polarization and inducing T cell differentiation.

Analytical and Antimicrobial Characterization of Zn-Modified Clays Embedding Thymol or Carvacrol.

Carvacrol and thymol are broad-spectrum natural antimicrobial agents. To reduce their volatility and improve their antimicrobial performance, synergistic systems were prepared loading the active molecules in zinc-modified clays. Montmorillonite (MMT) and zeolite (ZEO) were modified with zinc ions (ZnMMT and ZnZEO), with well-known antimicrobial properties, and then with carvacrol or thymol, reaching the 26 ± 3% and 33 ± 2% w/w of loading, respectively. The resulting hybrid materials were characterized by FT-IR, XPS, XRD, TGA, and GC-MS to evaluate carvacrol/thymol release in simulating food matrices. Antimicrobial assays carried out using spoiler and pathogenic bacterial strains showed that the antimicrobial activity of both thymol and carvacrol was largely preserved once they were loaded into Zn-modified clays. However, MMT hybrids showed an antibacterial activity significantly higher than ZEO hybrids at 50 mg/mL of thymol and carvacrol. For this reason, deeper antimicrobial evaluations were carried out only for ZnMMT composites. ZnMMT loaded with thymol or carvacrol produced inhibition zones against most of the target strains, also at 3.12 mg/mL, while the positive controls represented by the single molecule thymol or carvacrol were not active. The hybrid materials can be useful for applications in which the antimicrobial activity of natural molecules need to be displayed over time as requested for the control of microbial pathogens and spoilage bacteria in different applications, such as active packaging, biomaterials, and medical devices.

Protective Effects of Carvacrol on Mercuric Chloride-Induced Lung Toxicity Through Modulating Oxidative Stress, Apoptosis, Inflammation, and Autophagy.

Mercuric chloride (HgCl2) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl2 can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl2. Intraperitoneal injections of HgCl2 at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue's oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl2-induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co-administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF-κB, IκB, NLRP3, TNF-α, IL-1ß, IL6, COX-2, and iNOS were all reduced by CRV. When exposed to HgCl2, the levels of apoptotic Bax, caspase-3, Apaf1, p53, caspase-6, and caspase-9 increased, but the levels of antiapoptotic Bcl-2 reduced after CRV treatment. CRV decreased levels of Beclin-1, LC3A, and LC3B, which in turn decreased HgCl2-induced autophagy damage. After HgCl2 treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl2-induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative.

Protective Effect of Carvacrol against Oxidative Damage in Aged Rats.

BACKGROUND: Aging affects cellular functions and impairs tissue homeostasis. Carvacrol, a polyphenolic compound, has been shown to exert a wide range of pharmacological effects, such as antioxidant, anti-inflammatory, and anticancer characteristics. METHODS: This investigation aimed to evaluate the effect of carvacrol in elderly male rats. Carvacrol at a dose of 15 or 30 mg/kg was administrated daily per os for 60 days to aged rats. The liver, heart, and kidney samples were taken for the analysis of oxidative stress markers. Serum samples were used to evaluate liver enzymes (alanine transaminase (ALT) and aspartate aminotransferase (AST)). RESULTS: The levels of malondialdehyde (MDA) in the liver, heart, and kidney tissues of aged rats were higher. Conversely, the level of thiol was lower in the mentioned tissues than in the young control group. The levels of MDA in the liver, heart, and kidney tissues of aged rats were significantly reduced by carvacrol, which was accompanied by increased levels of total thiol. ALT and AST levels were higher in the serum of aged rats than in the young control ones. Carvacrol decreased ALT and AST levels in the serum of aged rats versus aged control rats. CONCLUSION: Carvacrol can be effective in protecting susceptible aged tissues and organs by increasing antioxidant defenses and decreasing liver enzymes.

Development of amphipathic derivatives of thymol and carvacrol as potent broad-spectrum antibacterial agents.

In the current study, to discover novel antibacterial agents, we designed and synthesized 72 carvacrol and thymol derivatives by biomimicking the structure and function of cationic antimicrobial peptides (AMPs). Many of the derivatives showed good antibacterial activity, and compound thy2I exhibited the most potent antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 0.5 µg/mL to 8 µg/mL. Compound thy2I could kill both gram-positive and gram-negative bacteria via a membrane-targeting mechanism of action with a low frequency of resistance. In addition, thy2I had the advantages of good membrane selectivity, low toxicity in vitro and in vivo, and good plasma stability. The in vivo activity results revealed that thy2I exhibited a positive therapeutic effect in a mouse skin abscess model induced by Staphylococcus aureus ATCC29213. After thy2I treatment (10 mg/kg), the bacterial load of the S. aureus-infected abscesses was reduced by approximately 99.65 %. Our study suggests that thy2I may serve as an antibacterial lead for further clinical evaluation.

Effects of Carvacrol on Cognitive Function and Apoptotic Gene Expression in Trimethyltin- Induced Hippocampal Injury in Rats.

OBJECTIVE: Trimethyltin (TMT) chloride is an organotin compound used in industry. It has been linked to generating reactive oxygen species (ROS), inflammatory processes, and neuronal death. Carvacrol is a monoterpene phenol found in the Lamiaceae plant family, modulating inflammatory conditions and necroptosis in neural tissue. This study aimed to investigate the neuroprotective effects of carvacrol in a rat model of hippocampal neuronal injury induced by TMT. MATERIALS AND METHODS: In this experimental study, sixty male Wistar rats were randomly divided into five groups (n=12): group 1 receiving saline, group 2 received dimethyl sulfoxide (DMSO) as a vehicle for 21 days, group 3 receiving a single dose of TMT (8 mg/kg) and groups 4 and 5 receiving carvacrol 40 and 70 mg/kg daily for 21 days after a single dose of TMT. All injections were intraperitoneal (I.P.). Caspase-3, Bax, Bcl-2, and Bdnf gene expression and the number of pyknotic neurons in the hippocampus were quantified. Spatial memory was assessed with a radial arm maze. RESULTS: Statistical analysis of histological data revealed the carvacrol significantly attenuated cognitive dysfunction and the number of pyknotic neurons in the hippocampal CA1 region of rats treated with TMT. Based on real-time polymerase chain reaction (PCR), carvacrol modulated the expression of genes involved in apoptosis (Bax and Caspase-3) and upregulated anti-apoptotic (Bcl-2) and brain derived neurotrophic factor (Bdnf) genes in the hippocampal tissue. CONCLUSION: These findings revealed neuroprotective effects of carvacrol which might be mediated by apoptotic and anti-apopetotic factors.

Biocontrol Mechanisms of Three Plant Essential Oils Against Phytophthora infestans Causing Potato Late Blight.

Late blight, caused by the notorious pathogen Phytophthora infestans, poses a significant threat to potato (Solanum tuberosum) crops worldwide, impacting their quality as well as yield. Here, we aimed to investigate the potential use of cinnamaldehyde, carvacrol, and eugenol as control agents against P. infestans and to elucidate their underlying mechanisms of action. To determine the pathogen-inhibiting concentrations of these three plant essential oils (PEOs), a comprehensive evaluation of their effects using gradient dilution, mycelial growth rate, and spore germination methods was carried out. Cinnamaldehyde, carvacrol, and eugenol were capable of significantly inhibiting P. infestans by hindering its mycelial radial growth, zoospore release, and sporangium germination; the median effective inhibitory concentration of the three PEOs was 23.87, 8.66, and 89.65 µl/liter, respectively. Scanning electron microscopy revealed that PEOs caused the irreversible deformation of P. infestans, resulting in hyphal shrinkage, distortion, and breakage. Moreover, propidium iodide staining and extracellular conductivity measurements demonstrated that all three PEOs significantly impaired the integrity and permeability of the pathogen's cell membrane in a time- and dose-dependent manner. In vivo experiments confirmed the dose-dependent efficacy of PEOs in reducing the lesion diameter of potato late blight. Altogether, these findings provide valuable insight into the antifungal mechanisms of PEOs vis-à-vis late blight-causing P. infestans. By utilizing the inherent capabilities of these natural compounds, we could effectively limit the harmful impacts of late blight on potato crops, thereby enhancing agricultural practices and ensuring the resilience of global potato food production.

Design of Novel TRPA1 Agonists Based on Structure of Natural Vasodilator Carvacrol-In Vitro and In Silico Studies.

Considering the escalating global prevalence and the huge therapeutic demand for the treatment of hypertension, there is a persistent need to identify novel target sites for vasodilator action. This study aimed to investigate the role of TRPA1 channels in carvacrol-induced vasodilation and to design novel compounds based on carvacrol structure with improved activities. In an isolated tissue bath experiment, it was shown that 1 µM of the selective TRPA1 antagonist A967079 significantly (p < 0.001) reduced vasodilation induced by 3 mM of carvacrol. A reliable 3D-QSAR model with good statistical parameters was created (R2 = 0.83; Q2 = 0.59 and Rpred2 = 0.84) using 29 TRPA1 agonists. Obtained results from this model were used for the design of novel TRPA1 activators, and to predict their activity against TRPA1. Predicted pEC50 activities of these molecules range between 4.996 to 5.235 compared to experimental pEC50 of 4.77 for carvacrol. Molecular docking studies showed that designed molecules interact with similar amino acid residues of the TRPA1 channel as carvacrol, with eight compounds showing lower binding energies. In conclusion, carvacrol-induced vasodilation is partly mediated by the activation of TRPA1 channels. Combining different in silico approaches pointed out that the molecule D27 (2-[2-(hydroxymethyl)-4-methylphenyl]acetamide) is the best candidate for further synthesis and experimental evaluation in in vitro conditions.

Shelf Life of Minced Pork in Vacuum-Adsorbed Carvacrol@Natural Zeolite Nanohybrids and Poly-Lactic Acid/Triethyl Citrate/Carvacrol@Natural Zeolite Self-Healable Active Packaging Films.

Enhancing food preservation and safety using environmentally friendly techniques is urgently needed. The aim of this study was to develop food packaging films using biodegradable poly-L-lactic acid (PLA) as biopolymer and carvacrol (CV) essential oil as an antioxidant/antibacterial agent for the replacement of chemical additives. CV was adsorbed onto natural zeolite (NZ) via a new vacuum adsorption method. The novel nanohybrid CV@NZ with a high CV content contained 61.7%wt. CV. Pure NZ and the CV@NZ nanohybrid were successfully dispersed in a PLA/triethyl citrate (TEC) matrix via a melt extrusion process to obtain PLA/TEC/xCV@NZ and PLA/TEC/xNZ nanocomposite films with 5, 10, and 15%wt CV@NZ or pure NZ content. The optimum resulting film PLA/TEC/10CV@NZ contained 10%wt. CV@NZ and exhibited self-healable properties, 22% higher tensile strength, 40% higher elongation at break, 45% higher water barrier, and 40% higher oxygen barrier than the pure PLA/TEC matrix. This film also had a high CV release content, high CV control release rate as well as 2.15 mg/L half maximal effective concentration (EC50) and 0.27 mm and 0.16 mm inhibition zones against Staphylococcus aureus and Salmonella enterica ssp. enterica serovar Typhimurium, respectively. This film not only succeeded in extending the shelf life of fresh minced pork, as shown by the total viable count measurements in four days but also prevented the lipid oxidation of fresh minced pork and provided higher nutritional values of the minced meat, as revealed by the heme iron content determination. It also had much better and acceptable sensory characteristics than the commercial packaging paper.

Study of Periodontal Bacteria in Diabetic Wistar Rats: Assessing the Anti-Inflammatory Effects of Carvacrol and Magnolol Hydrogels.

Periodontal disease and diabetes often co-occur; both are characterized by chronic inflammation. This study aimed to investigate the anti-inflammatory effects of carvacrol and magnolol when incorporated into a periodontal hydrogel and topically applied to Wistar rats with diabetes-associated periodontal disease. Forty male albino Wistar rats were divided into four groups: PD (induced diabetes and periodontitis), PDC (induced diabetes and periodontitis treated with carvacrol), PDM (induced diabetes and periodontitis treated with magnolol), and PDCM (induced diabetes and periodontitis treated with both carvacrol and magnolol). Post treatment, gingival tissue samples were collected to measure levels of the pro-inflammatory cytokines IL-6 and TNF-α. The PDCM group exhibited significantly lower levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) compared to the PD group. The combined application of a periodontal hydrogel containing carvacrol and magnolol may significantly reduce gingival inflammation in rats with diabetes-associated periodontal disease.

A carrier-free, injectable, and self-assembling hydrogel based on carvacrol and glycyrrhizin exhibits high antibacterial activity and enhances healing of MRSA-infected wounds.

Inspired by glycyrrhizin's strong pharmacological activities and the directed self-assembly into hydrogels, we created a novel carrier-free, injectable hydrogel (CAR@glycygel) by combining glycyrrhizin with carvacrol (CAR), without any other chemical crosslinkers, to promote wound healing on bacteria-infected skin. CAR appeared to readily dissolve and load into CAR@glycygel. CAR@glycygel had a dense, porous, sponge structure and strong antioxidant characteristics. In vitro, it showed better antibacterial ability than free CAR. For methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Escherichia coli, the diameter of inhibition zone values of CAR@glycygel were 3.80 ± 0.04, 3.31 ± 0.20 and 3.12 ± 0.24 times greater, respectively, than those of free CAR. The MICs for CAR@glycygel was 156.25 µg/mL while it was 1250.00 µg/mL for free CAR to these three bacteria. Its antibacterial mechanism appeared to involve destruction of the integrity of the bacterial cell wall and biomembrane, leading to a leakage of AKP and inhibition of biofilm formation. In vivo, CAR@glycygel effectively stopped bleeding. When applied to skin wounds on rats infected with MRSA, CAR@glycygel had strong bactericidal activity and improved wound healing. The wound healing rates for CAR@glycygel were 49.59 ± 15.78 %, 93.02 ± 3.09 % and 99.02 ± 0.55 % on day 3, day 7, and day 11, respectively, which were much better than blank control and positive control groups. Mechanisms of CAR@glycygel accelerating wound healing involved facilitating epidermis remolding, promoting the growth of hair follicles, stimulating collagen deposition, mitigating inflammation, and promoting angiogenesis. Overall, CAR@glycygel showed great potential as wound dressing for infected skin wounds.

Study of the Resistance of Staphylococcus aureus Biofilm, Biofilm-Detached Cells, and Planktonic Cells to Microencapsulated Carvacrol Used Alone or Combined with Low-pH Treatment.

Microbial biofilms pose severe problems in the medical field and food industry, as they are the cause of many serious infections and food-borne diseases. The extreme biofilms' resistance to conventional anti-microbial treatments presents a major challenge to their elimination. In this study, the difference in resistance between Staphylococcus aureus DSMZ 12463 biofilms, biofilm-detached cells, and planktonic cells against microcapsules containing carvacrol was assessed. The antimicrobial/antibiofilm activity of low pH disinfection medium containing the microencapsulated carvacrol was also studied. In addition, the effect of low pH on the in vitro carvacrol release from microcapsules was investigated. The minimum inhibitory concentration of microencapsulated carvacrol was 0.625 mg mL-1. The results showed that biofilms exhibited greater resistance to microencapsulated carvacrol than the biofilm-detached cells and planktonic cells. Low pH treatment alone, by hydrochloric acid addition, showed no bactericidal effect on any of the three states of S. aureus strain. However, microencapsulated carvacrol was able to significantly reduce the planktonic cells and biofilm-detached cells below the detection limit (no bacterial counts), and the biofilm by approximatively 3 log CFU mL-1. In addition, results showed that microencapsulated carvacrol combined with low pH treatment reduced biofilm by more than 5 log CFU mL-1. Thus, the use of microencapsulated carvacrol in acidic environment could be a promising approach to combat biofilms from abiotic surfaces.

Fleagrass (Adenosma buchneroides Bonati) Acts as a Fungicide Against Candida albicans by Damaging Its Cell Wall.

Fleagrass, a herb known for its pleasant aroma, is widely used as a mosquito repellent, antibacterial agent, and for treating colds, reducing swelling, and alleviating pain. The antifungal effects of the essential oils of fleagrass and carvacrol against Candida albicans were investigated by evaluating the growth and the mycelial and biofilm development of C. albicans. Transmission electron microscopy was used to evaluate the integrity of the cell membrane and cell wall of C. albicans. Fleagrass exhibited high fungicidal activity against C. albicans at concentrations of 0.5% v/v (via the Ras1/cAMP/PKA pathway). Furthermore, transmission electron microscopy revealed damage to the cell wall and membrane after treatment with the essential oil, which was further confirmed by the increased levels of ß-1,3-glucan and chitin in the cell wall. This study showed that fleagrass exerts good fungicidal and hyphal growth inhibition activity against C. albicans by disrupting its cell wall, and thus, fleagrass may be a potential antifungal drug.

Carvacrol protects rats against bleomycin-induced lung oxidative stress, inflammation, and fibrosis.

The main objective of this study was to investigate the potential efficacy of carvacrol (CAR) in mitigating bleomycin (BLM)-induced pulmonary fibrosis (PF). Sixty-six male Wistar rats were assigned into two main groups of 7 and 21 days. They were divided into the subgroups of control, BLM, CAR 80 (only for the 21-day group), and CAR treatment groups. The CAR treatment groups received CAR (20, 40, and 80 mg/kg, orally) for 7 or 21 days after an instillation of BLM (5 mg/kg, intratracheally). Results indicated that BLM significantly increased total cell count in bronchoalveolar lavage fluid and the percentages of neutrophils and lymphocytes, and reduced the percentage of macrophages. CAR dose-dependently decreased total cell count and the percentage of neutrophils and lymphocytes. CAR significantly reduced thiobarbituric acid reactive substances and hydroxyproline levels and elevated the total thiol level and catalase, superoxide dismutase, and glutathione peroxidase activities in BLM-exposed rats. Furthermore, CAR decreased the transforming growth factor-ß1, connective transforming growth factor, and tumor necrosis factor-α on days 7 and 21. BLM increased interferon-γ on day 7 but decreased its level on day 21. However, CAR reversed interferon-γ levels on days 7 and 21. Based on histopathological findings, BLM induced inflammation on days 7 and 21, but for induction of fibrosis, 21-day study showed more fibrotic injuries than the 7-day group. CAR showed the improvement of fibrotic injuries. The effect of CAR against BLM-induced pulmonary fibrosis is possibly due to its antioxidant, anti-inflammatory, and antifibrotic activity.

Evaluation of the Antibacterial, Anti-Inflammatory, And Bone-Promoting Capacity of UiO-66 Loaded with Thymol or Carvacrol.

Oral infectious diseases have a significant impact on the health of oral and maxillofacial regions, as well as the overall well-being of individuals. Carvacrol and thymol, two isomers known for their effective antibacterial and anti-inflammatory properties, have gained considerable attention in the treatment of oral infectious diseases. However, their application as topical drugs for oral use is limited due to their poor physical and chemical stability. UiO-66, a metal-organic framework based on zirconium ion (Zr4+), exhibits high drug loading capability. Carvacrol and thymol were efficiently loaded onto UiO-66 with loading rates of 79.60 ± 0.71% and 79.65 ± 0.76%, respectively. The release rates of carvacrol and thymol were 77.82 ± 0.87% and 76.51 ± 0.58%, respectively, after a period of 72 h. Moreover, Car@UiO-66 and Thy@UiO-66 demonstrated excellent antibacterial properties against Candida albicans, Escherichia coli, and Staphylococcus aureus with minimum bactericidal concentrations (MBC) of 0.313 mg/mL, 0.313 mg/mL, and 1.25 mg/mL, respectively. Furthermore, based on the results of the CCK8 cytotoxicity assay, even at concentrations as high as 1.25 mg/mL, Car@UiO-66 and Thy@UiO-66 exhibited excellent biocompatibility with a relative cell survival rate above 50%. These findings suggest that Car@UiO-66 and Thy@UiO-66 possess favorable biocompatibility properties without significant toxicity towards periodontal membrane cells. Additionally, in vivo studies confirmed the efficacy of Car@UiO-66and Thy@UiO-66 in reducing inflammation, promoting bone formation through inhibition of TNF-a and IL6 expression, enhancement of IL10 expression, and acceleration of bone defect healing. Therefore, the unique combination of antibacterial, anti-inflammatory, and osteogenic properties make Car@UiO-66 and Thy@Ui O-66 promising candidates for the treatment of oral infectious diseases and repairing bone defects.

Effects of essential oil of Origanum onites and its major component carvacrol on the expression of toxicity pathway genes in HepG2 cells.

BACKGROUND: Origanum species have been used in various commercial constructions as a remedy against burns and wounds, agriculture, alcoholic drinks, fragrance, and flavoring substances of food products. The essential oil of Origanum onites L. (EOOO) and its component carvacrol (CV) possesses a wide range of biological activities including anti-cancer activity. PURPOSE: The purpose of this study was to investigate the growth inhibitory activity of the essential oil and its major component CV and then hepatotoxicity pathway-related genes in HepG2 cells. METHODS: The effects of the EOOO and CV on cell growth and mRNA expressions of 84 hepatotoxicity pathway-related genes were investigated in HepG2, using trypan blue exclusion/ bromodeoxyuridine (BrdU) incorporation tests and real-time-polymerase chain reaction (RT-PCR) array, respectively. RESULTS: The EOOO and CV inhibited cell growth with IC50 values of 0.08 µg/mL and 45 µg/mL, respectively, after 24 h. Real-time, reverse-transcription-polymerase chain reaction (RT2-PCR) array analysis revealed that expressions of 32 genes out of 84 were changed at least 2-fold or more in the EOOO-treated cells. Among them, expression levels of 17 genes were elevated, while expression levels of 15 genes were diminished. Furthermore, after exposure of cells to 45 µg/mL of CV, the expression of 8 genes was increased while the other 8 genes were decreased. Both the EOOO and carvacrol affected the expression of 48 genes of HepG2 cells which are involved in the hepatotoxicity pathway, indicating their hepatoprotective and possible anti-hepatocarcinogenic effects. CONCLUSION: The present study demonstrates that the essential oil of Origanum onites and carvacrol can be used in various applications such as anticancer or herbal drugs, since its non-hepatotoxicity.

Investigation of the Antitrichomonal Activity of Cinnamaldehyde, Carvacrol and Thymol and Synergy with Metronidazole.

Objective: Trichomonas vaginalis is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic disease, but there is a need for new drugs since 1980's with increasing numbers of reported resistance. In this study, it was aimed to determine the antitrichomonal activity of the major components of Cinnamomum zeylanicum (cinnamon) and Thymus vulgaris (thyme) essential oils, cinnamaldehyde, carvacrol and thymol against metronidazole resistant and susceptible T. vaginalis strains, and to determine their interaction with metronidazole by checkerboard method. Methods: Cinnamaldehyde, carvacrol, thymol and metronidazole were obtained commercially. Two clinical isolates and one metronidazole resistant T. vaginalis reference strain were used in the study. MIC50 and MLC values of essential oil components and metronidazole were determined by broth microdilution method. The combinations of essential oil components with metronidazole were determined by the checkerboard method. Results: According to in vitro activity tests, cinnamaldehyde was determined to be most effective essential oil component. Clinical isolates were susceptible to metronidazole. In combination study, metronidazole showed synergy with cinnamaldehyde and carvacrol, and partial synergy with thymol. Conclusion: It was determined that cinnamaldehyde, carvacrol and thymol, which are known to have high antimicrobial activity, also have strong activity against T. vaginalis isolates and show a synergistic interaction with metronidazole. The use of metronidazole at lower doses in the synergistic interaction may contribute to the literature in terms of reducing drug side effects, creating a versatile antimicrobial target, and reducing the rate of resistance development.

Citrus oil gland and cuticular wax inspired multifunctional gelatin film of OSA-starch nanoparticles-based nanoemulsions for preserving perishable fruit.

Inspired by the citrus oil gland and cuticular wax, a multifunctional material that stably and continuously released the carvacrol and provided physical defenses was developed to address issues of fresh-cut fruits to microbial infestation and moisture loss. The results confirmed that low molecular weight and loose structure of starch nanoparticles prepared by the ultrasound-assisted Fenton system were preferable for octenyl succinic anhydride modification compared to native starch, achieving a higher degree of substitution (increased by 18.59 %), utilizing in preparing nanoemulsions (NEs) for encapsulating carvacrol (at 5 % level: 81.58 %). Furthermore, the NEs-based gelatin (G) film improved with surface hydrophobic modification by myristic acid (MA) successfully replicated the citrus oil gland and cuticular wax, providing superior antioxidant (enhanced by 3-4 times) and antimicrobial properties (95.99 % and 84.97 % against Staphylococcus aureus and Escherichia coli respectively), as well as the exceptional UV shielding (nearly 0 transmittance in the UV region), mechanical (72 % increase in tensile strength), and hydrophobic (WCA 133.63°). Moreover, the 5%NE-G@MA film inhibited foodborne microbial growth (reduced by 50 %) and water loss (controlled below 15 %), extending the shelf life of fresh-cut navel orange and kiwi. Thus, the multifunctional film was a potential shield for preserving perishable fresh-cut products.

Evaluation of the activity and mechanisms of oregano essential oil against PRV in vivo and in vitro.

BACKGROUND: The Pseudorabies Virus (PRV) leading to pseudorabies and causes huge economic losses in pig industry. The development of novel PRV variations has diminished the efficacy of traditional vaccinations, and there is yet no medication that can stop the spread of PRV infection. Therefore, PRV eradication is challenging. Oregano essential oil, the plant-based ingredient for medication feed have been shown to has strong anti-herpesvirus activity, but no anti-PRV function has been reported. RESULTS: The current study assessed the anti-pseudorabies virus (PRV) activity of oregano essential oil and explored its mechanisms and most effective components against PRV. Our in vivo findings demonstrated that oregano essential oil could decrease the PRV load in tissues, mitigate tissue lesions, and enhance the survival rate of mice. The potential antiviral mechanism involves augmenting humoral and cellular immune responses in PRV-infected mice. To further investigate the most effective components of oregano essential oil against PRV, an in vitro study was conducted, revealing that oregano essential oil and its main constituents, carvacrol and thymol, all diminished PRV intracellular proliferation in vitro. Carvacrol exhibited the most potent anti-PRV effect, serving as the primary contributor to oregano essential oil's anti-PRV activity. The mechanisms underlying carvacrol's anti-PRV properties include the upregulation of cytokines TNF-α, IFN-ß, IFN-γ, IL-12, and the inhibition of PRV-induced apoptosis in BHK-21 cells. CONCLUSIONS: Our study provides an effective drug for the prevention and control of PRV infection.