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Abstract Background Paraquat (PQ) is a widely used pesticide, can cause severe intoxication and respiratory failure. Myrtenol (Mrl), an essential oil derived in various plants, exhibits several biological properties, including anti-inflammatory and antioxidant activities. This study aims to investigate the protective potential of Mrl against oxidative stress and inflammation caused by PQ exposure. Methods Twenty-five Wistar albino rats were divided into the following groups (n = 5 in each group): a control group (treated by dimethyl sulfoxide (DMSO)), a PQ group (exposed to 54 mg/m³ aerosol PQ), and two treatment groups that were exposed to PQ aerosol and administered oral Mrl at doses of 25 mg/kg/day and 50 mg/kg/day, respectively. The final group was exposed to PQ aerosol and treated with oral dexamethasone at a dose of 0.03 mg/kg/day. Various hematological, oxidative, inflammatory, and pathological indices were measured at the conclusion of the treatment period. Results PQ decreases the levels or activities of superoxide dismutase (SOD), catalase (CAT), and Thiol, while increasing the levels or activities of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA). Mrl restored activites of SOD, and CAT, as well as thiol levels to near-control values while reducing TNF-α, IL-6, and MDA levels. Pathological studies further confirmed the therapeutic effects of Mrl. Conclusion The results of this study demonstrate the promising therapeutic effects of Mrl against inhaled PQ in rats.

Purpose: Dracocephalum kotschyi Boiss. belongs to the Lamiaceae family, is one of the important and endangered endemic species in Iran. The present study was conducted to investigate the effects of micronutrient elements application on the content and composition of essential oil of D. kotschyi Boiss. shoots in southwestern Iran (Shahrekord) in 2022 and 2023. Research Methods: Four foliar fertilizers including Fe, Cu, Zn and Mn were applied in 0, 20, 40 and 60 mg.l-1 in RCBD design by factorial layout and 3 replications. Findings: Results obtained from gas chromatography/mass spectrometry (GC-MS) showed 14 essential oil components. According to obtained results, applied micronutrients significantly influenced the essential oil content/ composition of D.kotschyi. In both years, the highest content of essential oil (0.98-0.99 %) was obtained in plants treated with 40 mg.l-1of micronutrients (Fe2Cu2Zn2Mn2) and the lowest content (0.59-0.66%) made by control plants (0 mg.l-1), however the plants treated by 60 mg.l-1of micronutrients in most characters were in a same group with the control plants. The most important chemical compounds that determine the quality of D. kotschyi essential oil including Neral (9.02-16.31%), Limonene (25.4-35.6%), Geranial (8.6-16.5%), Eucalyptol (3.89-8.01%) and Myrtenol (22.5-32.1%) were identified alcoholic monoterpenes. Limonene belonging to monoterpene hydrocarbons was the predominant constituent of the D. kotschyi. Limitations: There were no limitations to the report. Originality/Value: The foliar application of micronutrients at 40 mg.l-1 (Fe, Cu, Zn and Mn) can be a good strategy to improve the essential oil quantity and quality of D.kotschyi in cold and semi-arid climates.

Background and objectives: Cisplatin is an effective anticancer drug which has some side effects such as acute kidney injury. Myrtenol, a monoterpene alcohol which is found in some plants, has various pharmacological effects including anti-inflammatory and antioxidant activities. In this study, we evaluated the nephroprotective effects of myrtenol in acute kidney injury induced by cisplatin in male mice. Methods: In this experimental in-vivo study, 35 male mice were randomly separated into 5 groups, including control, CIS (20 mg/kg cisplatin, intraperitoneally on day 1), dimethyl sulfoxide (DMSO; received cisplatin only on day 1, plus DMSO 1% on the first day, continued for 3 days), and treatment groups (received cisplatin only on day 1, plus myrtenol 25 mg/kg and 50 mg/kg intraperitoneally on the first day, continued for 3 days). The blood urea nitrogen (BUN) levels were evaluated in serum. The renal tissues were collected for evaluating malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities; histopathological investigation was also performed. Results: Our results showed that cisplatin administration caused significant elevation in the levels of renal MDA and serum BUN; in contrast, renal SOD and CAT activities significantly reduced. Myrtenol treatment, especially 50 mg/kg for four consecutive days mitigated these alternations in serum and renal tissue. Also, the kidney’s histopathological investigations were consistent with biochemical and oxidative parameters. Conclusion: The results of our study revealed that myrtenol ameliorates acute kidney injury induced by cisplatin via oxidative stress suppression.

Atmospheric new particle formation (NPF) is an important source of aerosol particles and cloud condensation nuclei, which affect both climate and human health. In pristine environments, oxidation of biogenic volatile organic compounds (VOCs) is a major contributor to NPF. However, the impact of relative humidity (RH) on NPF from these precursors remains poorly understood. Herein, we report on NPF, as inferred from measurements of total particle number density with a particle diameter (dp) > 7 nm, from three VOCs (sabinene, α-terpineol, and myrtenol) subjected to dark ozonolysis. From a series of comparative experiments under humid (60% RH) and dry (~0% RH) conditions and a variety of VOC mixing ratios (ξVOC, parts per billion by volume, ppbv), we show varied behavior in NPF at elevated RH depending on the VOC and ξVOC. In general, RH-dependent enhancement of NPF at an ξVOC between v and 20 ppbv was observed for select VOCs. Our results suggest that gaseous water at particle genesis enhances NPF by promoting the formation of low-volatility organic compound gas-phase products (LVOCs). This is supported by measurements of the rate of NPF for α-pinene-derived SOA, where RH had a greater influence on the initial rate of NPF than did ξVOC and ξO3.

The syntheses of the title compounds were performed using lauric and myristic acids. The compounds obtained were characterized using 1H-, 13C-NMR and 2D 1H-1H COSY, 1H-13C HSQC NMR, IR, and high-resolution mass spectrometry. Both compounds exhibited bactericidal activity on S. aureus comparable to that of a reference drug (miramistin). Compound 10, with lauric acid fragment, had a 16-fold higher activity on P. aeruginosa compared to compound 11, which in turn contains myristic acid fragment (with minimum inhibitory concentrations of 32 and 512 μg/mL, respectively). Compound 11 exhibited a pronounced activity against all types of fungi (higher than the activity of miramistin), while the activity of compound 10 was considerably lower. Thus, compound 11 can serve as a promising antimicrobial agent for the treatment of various fungal and staphylococcal infections, while compound 10 is of interest to treat P. aeruginosa-associated infections.

Lei Liu,1,2,* Bin Liu,1,2,* Liang Li,1,2 Ming-Xin He,2 Xiang-Dong Zhou,1,2 Qi Li1,2 1Department of Respiratory Medicine, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People’s Republic of China; 2NHC Key Laboratory of Tropical Disease Control, Hainan Medical University, Haikou, Hainan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi Li, Email lqlq198210@sina.comBackground: blaNDM-1-producing Acinetobacter baumannii (BP-AB) remains a critical problem in nosocomial infections, because of its resistance mediated by the biofilm formation and virulence factors. No studies have confirmed myrtenol’s efficacy in inhibiting the biofilm formation and virulence associated with biofilm of BP-AB.Methods: The tested concentrations of myrtenol were wild type (A), 50 μg/mL (B), 100 μg/mL (C), 200 μg/mL (D), 250 μg/mL (E), and 300 μg/mL (F).Results: The BP-AB biofilm inhibition was significantly higher in the D, E, and F groups than in the A, B, and C groups. Myrtenol significantly reduced the air-liquid interface ring formation in glass tubes. It also effectively inhibited the attachment of BP-AB strains on polystyrene surfaces as shown by crystal violet staining. Microscopy showed a significant reduction in biofilm formation with dispersed BP-AB strains. The confocal laser scanning microscopy analysis showed a significant reduction in the biofilm’s biomass, covered surface area, and thickness. The scanning electron microscopy analysis revealed significantly fewer BP-AB aggregates on the coverslip surface. In the CompStat analysis, the biofilm’s biomass, maximum thickness, and surface-to-volume ratio were significantly reduced. The qPCR analysis revealed a significant down-regulation of bfmR, bap, csuA/B, and ompA expression, which positively correlated with the biofilm’s biomass, maximum thickness, and surface-to-volume ratio in BP-AB strains. Myrtenol significantly improved the susceptibility of BP-AB to the antibiotics amikacin, piperacillin/tazobactam, cefoperazone/sulbactam, and ceftazidime.Conclusion: Myrtenol attenuates the BP-AB biofilm formation and virulence by suppressing the expression of bfmR, bap, csuA/B, and ompA.Keywords: Acinetobacter baumannii, myrtenol, biofilm, virulence factors, resistance

We assessed the anti-inflammatory, anti-oxidative and anti-remodeling impacts of a synthesized myrtenol-loaded niosome in rats with allergic asthma. Forty-nine rats were divided into seven groups of control, vacant niosome (VN), Asthma, Asthma+VN, Asthma+SM (simple myrtenol), Asthma+NM (niosomal myrtenol, 8 mg/kg), and Asthma+B (budesonide, 41 μg). Ovalbumin-induced asthmatic animals were exposed to daily inhalation of drug/vehicle for one week. Histopathology and inflammatory and oxidative stress indices in the lungs were assessed. Myrtenol-loaded niosomes showed appropriate physicochemical properties. Airway smooth muscle thickness, inflammatory cell infiltration, goblet cell hyperplasia, NO, IL-17, and MDA level decreased, and IL-10 and TAC levels increased in tissue and/or BALF of treatment groups. Niosomal myrtenol showed high potency comparable to budesonide in alleviating disease parameters. In conclusion, inhalation of niosomal myrtenol ameliorated inflammation, oxidative stress and tissue remodeling in asthmatic animals more potently than simple myrtenol and could be a target for production of an anti-asthmatic medicine.

The synthesis of the title compounds was performed from (-)-cis-myrtanic and (-)-myrtenic acids. The compounds obtained were characterized using 1H- and 13C-NMR, IR, and high-resolution mass spectrometry. Despite the presence of quaternary ammonium moiety, both compounds had moderate antimicrobial activity with a MIC of 128 µg/mL on S. aureus and 512 µg/mL on E. coli. The antifungal activity was low on Candida isolates, while also comparable with conventional antimycotic (Fluconazole) on filamentous fungi. These data suggest that two bulky bicyclic terpene fragments apparently both increase lipophilicity and close the quaternary ammonium moiety located in the center of molecules and thus drastically decrease the antimicrobial potential of bipharmacophore.

Orofacial pain is one of the commonest and most complex complaints in dentistry, greatly impairing life quality. Preclinical studies using monoterpenes have shown pharmacological potential to treat painful conditions, but the reports of the effects of myrtenol on orofacial pain and inflammation are scarce. The aim of this study was to evaluate the effect of myrtenol in experimental models of orofacial pain and inflammation. Orofacial nociceptive behavior and the immunoreactivity of the phosphorylated p38 (P-p38)-MAPK in trigeminal ganglia (TG) and spinal trigeminal subnucleus caudalis (STSC) were determined after the injection of formalin in the upper lip of male Swiss mice pretreated with myrtenol (12.5 and 25 mg/kg, i.p.) or vehicle. Orofacial inflammation was induced by the injection of carrageenan (CGN) in the masseter muscle of mice pretreated with myrtenol (25 and 50 mg/kg, i.p.) or its vehicle (0.02% Tween 80 in saline). Myeloperoxidase (MPO) activity and histopathological changes in the masseter muscle and interleukin (IL)-1β levels in the TG and STSC were measured. The increase in face-rubbing behavior time induced by formalin and P-p38-MAPK immunostaining in trigeminal ganglia were significantly reduced by myrtenol treatment (12.5 and 25 mg/kg). Likewise, increased MPO activity and inflammatory histological scores in masseter muscle, as well as augmented levels of IL-1β in the TG AND STSC, observed after CGN injection, were significantly decreased by myrtenol (25 and 50 mg/kg). Myrtenol has potential to treat orofacial inflammation and pain, which is partially related to IL-1β levels in the trigeminal pathway and p38-MAPK modulation in trigeminal ganglia.

Infectious diseases caused by various nosocomial microorganisms affect worldwide both immunocompromised and relatively healthy persons. Bacteria and fungi have different tools to evade antimicrobials, such as hydrolysis damaging the drug, efflux systems, and the formation of biofilm that significantly complicates the treatment of the infection. Here, we show that myrtenol potentiates the antimicrobial and biofilm-preventing activity of conventional drugs against S. aureus and C. albicans mono- and dual-species cultures. In our study, the two optical isomers, (−)-myrtenol and (+)-myrtenol, have been tested as either antibacterials, antifungals, or enhancers of conventional drugs. (+)-Myrtenol demonstrated a synergistic effect with amikacin, fluconazole, and benzalkonium chloride on 64–81% of the clinical isolates of S. aureus and C. albicans, including MRSA and fluconazole-resistant fungi, while (−)-myrtenol increased the properties of amikacin and fluconazole to repress biofilm formation in half of the S. aureus and C. albicans isolates. Furthermore, myrtenol was able to potentiate benzalkonium chloride up to sixteen-fold against planktonic cells in an S. aureus–C. albicans mixed culture and repressed the adhesion of S. aureus. The mechanism of both (−)-myrtenol and (+)-myrtenol synergy with conventional drugs was apparently driven by membrane damage since the treatment with both terpenes led to a significant drop in membrane potential similar to the action of benzalkonium chloride. Thus, due to the low toxicity of myrtenol, it seems to be a promising agent to increase the efficiency of the treatment of infections caused by bacteria and be fungi of the genus Candida as well as mixed fungal–bacterial infections, including resistant strains.

The increased incidence of mixed infections requires that the scientific community develop novel antimicrobial molecules. Essential oils and their bioactive pure compounds have been found to exhibit a wide range of remarkable biological activities and are attracting more and more attention. Therefore, the aim of this study was to evaluate myrtenol (MYR), one of the constituents commonly found in some essential oils, for its potential to inhibit biofilms alone and in combination with antimicrobial drugs against Candida auris/Klebsiella pneumoniae single and mixed biofilms. The antimicrobial activity of MYR was evaluated by determining bactericidal/fungicidal concentrations (MIC), and biofilm formation at sub-MICs was analyzed in a 96-well microtiter plate by crystal violet, XTT reduction assay, and CFU counts. The synergistic interaction between MYR and antimicrobial drugs was evaluated by the checkerboard method. The study found that MYR exhibited antimicrobial activity at high concentrations while showing efficient antibiofilm activity against single and dual biofilms. To understand the underlying mechanism by which MYR promotes single/mixed-species biofilm inhibition, we observed a significant downregulation in the expression of mrkA, FKS1, ERG11, and ALS5 genes, which are associated with bacterial motility, adhesion, and biofilm formation as well as increased ROS production, which can play an important role in the inhibition of biofilm formation. In addition, the checkerboard microdilution assay showed that MYR was strongly synergistic with both caspofungin (CAS) and meropenem (MEM) in inhibiting the growth of Candida auris/Klebsiella pneumoniae-mixed biofilms. Furthermore, the tested concentrations showed an absence of toxicity for both mammalian cells in the in vitro and in vivo Galleria mellonella models. Thus, MYR could be considered as a potential agent for the management of polymicrobial biofilms.

Methicillin-resistant Staphylococcus aureus (MRSA) is a deleterious human pathogen responsible for severe morbidity and mortality worldwide. The pathogen has attained high priority in the World Health Organization (WHO) – Multidrug-resistant (MDR) pathogens list. Emerging MDR strains of S. aureus are clinically challenging due to failure in conventional antibiotic therapy. Biofilm formation is one of the underlying mechanisms behind the antibiotic resistance. Hence, attenuating biofilm formation has become an alternative strategy to control persistent infections. The current study is probably the first that focuses on the antibiofilm and antivirulence potential of myrtenol against MRSA and its clinical isolates. Myrtenol exhibited a concentration-dependent biofilm inhibition without causing any harmful effect on cell growth and viability. Further, microscopic analysis validated the biofilm inhibitory efficacy of myrtenol against MRSA. In addition, myrtenol inhibited the synthesis of major virulence factors including slime, lipase, α-hemolysin, staphyloxanthin and autolysin. Inhibition of staphyloxanthin in turn sensitized the MRSA cells to healthy human blood and hydrogen peroxide (H2O2). Notably, myrtenol treated cells were deficient in extracellular DNA (eDNA) mediated autoaggregation as eDNA releasing autolysis was impaired by myrtenol. Biofilm disruptive activity on preformed biofilms was observed at concentrations higher than minimum biofilm inhibitory concentration (MBIC) of myrtenol. Also, the non-cytotoxic effect of myrtenol on human peripheral blood mononuclear cell (PBMC) was evidenced by trypan blue and Alamar blue assays. Transcriptional analysis unveiled the down-regulation of global regulator sarA and sarA mediated virulence genes upon myrtenol treatment, which is well correlated with results of phenotypic assays. Thus, the results of the present study revealed the sarA mediated antibiofilm and antivirulence potential of myrtenol against MRSA.

The increase in Staphylococcus aureus resistance to conventional antibacterials and persistent infections related to biofilms, as well as the low availability of new antibacterial drugs, has made the development of new therapeutic alternatives necessary. Medicinal plants are one of the main sources of bioactive molecules and myrtenol is a natural product with several biological activities, although its antimicrobial activity is little explored. Based on this, the objective of this study was to evaluate the antibacterial activity of myrtenol against S. aureus, determining the minimum inhibitory and bactericidal concentrations (MIC and MBC), investigating the possible molecular target through the analysis of molecular docking. It also aimed to evaluate the effect of its combination with antibacterial drugs and its activity against S. aureus biofilms, in addition to performing an in silico analysis of its pharmacokinetic parameters. Myrtenol showed MIC and MBC of 128 µg/mL (bactericidal action) and probably acts by interfering with the synthesis of the bacterial cell wall. The effects of the association with antibacterials demonstrate favorable results. Myrtenol has remarkable antibiofilm activity and in silico results indicate a good pharmacokinetic profile, which make myrtenol a potential drug candidate for the treatment of infections caused by S. aureus.

The essential oils of leaves and flowers Achillea wilhelmsii (compositae) collected from the suburb of Neka, north of Iran, in June 2001, were isolated by hydrodistillation and analyzed by means of GC and GC/MS. Fifteen and nineteen components were identified in the oils of the leaves and flowers of Achillea wilhelmsii, respectively. The major constituents of the essential oil of the leaves of A. wilhelmsii were camphor (24.1%), 1,8-cineole (22.3), borneol (11.1) and myrtenol (8.5%). The major constituents of the essential oil of the flowers of A. wilhelmsii were camphor (21.2%), myrtenol (14.4%), myrtenyl acetate (8.9%), yomogi alcohol (8.7%) and borneol (8.2%).