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.
CONCLUSIONS: Carvacrol can be effective in protecting susceptible aged tissues and organs by increasing antioxidant defenses and decreasing liver enzymes.

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.

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.

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-1β, 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.

The effects induced by medicinal aromatic plants in biological systems vary with the type and amount of bioactive substances these plants contain. Whether the purified form of the main chemical components of these plants, such as carvacrol and thymol, or plant volatile oils containing tens of bioactive compounds are more effective remains a question of debate. This study was aimed at providing a comparative assessment of the effects of Origanum syriacum L. (wild mountain thyme) volatile oil (OSVO) and one of its main components, carvacrol (CRV), on the in vitro ruminal degradability of lucerne herbage and methane production during the degradation of lucerne. For this purpose, wild thyme was harvested at the beginning of the flowering period, and the OSVO was extracted from the plant by steam distillation. Gas production assays were performed in five groups of ruminal fluid samples, one of which was maintained for control purposes, and the other four 40/60/80 mg/l of OSVO and 60 mg/l of CRV were added. Compared to the control group, in the samples with the added CRV and OSVO, the amounts of in vitro total gas and methane production were observed to have been affected, but no decrease was detected in the ruminal protozoa counts. The level of ammonia nitrogen was lowest in the groups, in which CRV and 40 mg/l of OSVO (P < 0.01) were added. The ruminal protozoa counts were not affected by the addition of CRV and OSVO. While the total volatile fatty acid (TVFA) and propionic acid (PA) concentrations in the in vitro fermentation fluid of lucerne herbage were low in all the groups, butyric acid was detected at a level of 40 mg/l in the group where CRV was added. The OSVO was ascertained to have induced dose-dependent alterations in the investigated in vitro digestion parameters. In result, CRV (60 mg/l) and OSVO (40 mg/l) were determined to have shown a relatively positive effect on the in vitro ruminal gas production. The anti-methanogenic effect of the plant extracts was due to the decreased digestibility of the lucerne herbage. This can have a positive impact on the environment, but the same cannot be said for the animal nutrient use and animal performance.

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.
CONCLUSIONS: 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.

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.

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.
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.
CONCLUSIONS: These findings revealed neuroprotective effects of carvacrol which might be mediated by apoptotic and anti-apopetotic factors.

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.

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.