Search

Lung atypical adenomatous hyperplasia (AAH) is a forerunner of pulmonary adenocarcinoma. The drugs being utilized in the remediation of this type of hyperplasia have some adverse impacts. The present research focused on the potential anti-hyperplasia effect of myrtenol, an herbal terpenoid, on urethane-induced lung AAH in rats. Rats were injected with urethane (1.5 g/kg) thrice at 48 h intervals, and 20 weeks later, the animals were treated with 50 mg/kg myrtenol intraperitoneally once a day for 1 week. The ELISA method was used to measure inflammatory cytokines and oxidative parameters in the lung tissue and bronchoalveolar lavage fluid (BALF). The expression of NFκB and apoptotic/antiapoptotic factors (P53/Bcl-2) was evaluated by western blot and immunohistochemistry, respectively. H&E staining was performed for histopathological investigation. Histopathology confirmed the anti-hyperplasia effect of myrtenol, which was evidenced by the reduction of bronchoalveolar wall thickness and inflammation score. It also decreased hyperplasia progression by reducing Bcl-2, IL-10, p53, and Ki67. Compared with the urethane group, myrtenol normalized the activity of the oxidative stress markers malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Moreover, it showed an anti-inflammatory effect by decreasing lung and BALF IL-1β levels and NFκB expression. Myrtenol may have a promising effect on lung cancer treatment by counteracting lung hyperplasia via modulation of inflammation, oxidative stress, and apoptosis. Myrtenol could reduce hyperplasia and inflammation and increase apoptosis in urethane-induced lung hyperplasia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

A simple and efficient synthesis of cis- and trans-myrtanic acids in preparative yields of 54–58% and 72–74%, respectively, was proposed and consisted of oxidation of cis- and trans-myrtanols by CrO3–AcOH upon addition of the oxidant to a solution of the starting alcohols at room temperature. Tests of the obtained compounds for antifungal activity showed lower activity for the quaternary salts than for the starting acids and greater efficacy for the cis-isomers than for the trans-isomers. However, the alcohols themselves, i.e., cis- and trans-myrtanols and (–)-myrtenol, had the greatest activities. [ABSTRACT FROM AUTHOR]

This research investigated the preventive effects of myrtenol (MYR), fatty acid nanocarriers (FANC), and myrtenol‐loaded FANC (MYR + FANC) on neurological disturbance, stroke volume, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and tumor necrosis factor‐alpha (TNF‐α) in the brain with ischemia–reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in rats. Seventy two Wistar male rats were divided into six main groups. The groups were sham, ischemia–reperfusion group (MACO), MACO‐MYR (50 mg/kg), MACO‐FANC (50 and 100 mg/kg), and MACO‐MYR + FANC (50 mg/kg). Stroke volume, neurological deficit scores, and the brain levels of MDA, SOD, and TNF‐α were examined with TTC staining, observation, and ELISA, respectively. Pretreatment with MYR, FANC (100 mg/kg), and MYR + FANC reduced the neurological deficit score and cerebral infarction volume. MYR, FANC (100 mg/kg), and MYR + FANC pretreatment increased and decreased brain SOD and MDA levels compared to MACO group, respectively. The TNF‐α level decreased in the MYR + FANC group compared to MCAO and MCAO‐MYR groups in the brain. The use of FANC (100 mg/kg), MYR, and MYR + FANC has protective effects against oxidative stress and ischemia–reperfusion injury. FANC probably improve the bioavailability of MYR, as MYR+ FANC had more therapeutic effects on the reduction of ischemia–reperfusion injuries, inflammation, and oxidative stress. [ABSTRACT FROM AUTHOR]

Asthma is an inflammatory disorder with significant health problems. It generally affects the lungs but can also impact brain performance via several mechanisms. Some investigations have proposed that asthma impairs cognition. This study assessed the impacts of myrtenol as a monoterpene on cognitive disorders following asthma at behavioral, molecular, and synaptic levels. Asthma was induced by injection and inhalation of ovalbumin (OVA). Male Wistar rats were allocated to five groups: control, asthma, asthma/vehicle, asthma/myrtenol, and asthma/budesonide. Myrtenol (8 mg/kg) or budesonide (160 μg/kg) was administered through inhalation once a day for 1 week, and at the end of the inhalation period, behavioral tests (MWM and Open Field), field potential recording, hippocampal brain-derived neurotrophic factor (BDNF), IL1β (ELISA), and NFκB measurement (Western blot) were performed to evaluate cognitive performance. Moreover, H&E (hematoxylin and eosin) staining was used for hippocampus histological evaluation. Myrtenol improved spatial learning, memory, LTP (long-term potentiation) impairments, and anxiety-like behaviors following asthma. Myrtenol inhalation increased the BDNF level and decreased the IL1β level and NFκB expression in the hippocampus of the asthmatic rats. The neuronal damage in the hippocampus following allergic asthma was alleviated via myrtenol administration. Myrtenol, as an herbal extract, protects the hippocampus from asthma consequences. Our observations revealed that myrtenol can improve spatial learning, memory, synaptic plasticity impairments, and anxiety-like behaviors following asthma. We believe that these ameliorating effects of myrtenol can be attributed to inflammation suppression and increased BDNF in the hippocampus. [ABSTRACT FROM AUTHOR]

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 <1 ppbv 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. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury (IRI) is directly related to forming reactive oxygen species, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and cytokines. Niosomes are nanocarriers and an essential part of drug delivery systems. We aimed to investigate the effects of myrtenol's inhaled and intraperitoneal niosomal form, compared to its simple form, on lung ischemia reperfusion injury (LIRI). Wistar rats were divided into ten groups. Simple and niosomal forms of myrtenol were inhaled or intraperitoneally injected daily for one week prior to LIRI. We evaluated oxidative stress, apoptotic, and inflammatory indices, nitric oxide, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and histopathological indices. Pretreatment with simple and niosomal forms of myrtenol significantly inhibited the indices of pulmonary edema, pro-inflammatory cytokines and proteins, oxidant agents, nitric oxide, iNOS, apoptotic proteins, congestion of capillaries, neutrophil infiltration, and bleeding in the alveoli. Furthermore, myrtenol increased anti-inflammatory cytokines, anti-oxidants agents, eNOS, anti-apoptotic proteins and the survival time of animals. The niosomal form of myrtenol showed a more ameliorative effect than its simple form. The results showed the superior protective effect of the inhalation of myrtenol niosomal form against LIRI compared to its simple form and systemic use. (A); Timeline of the study, (B); heating method to make niosomes, (C); lung ischemia-reperfusion method, (D); bronchoalveolar fluid collection method, (E); summary of study findings. [Display omitted] • Inhalation and intraperitoneal injection of myrtenol in both simple and niosomal forms prevented increased edema, histopathological indices, and apoptotic cells in ischemia-reperfusion-induced lung injury in rats. • Inhalation and intraperitoneal administration of myrtenol in both forms prevented the increase in oxidant agents and pro-inflammatory cytokines and the decrease in antioxidants and anti-inflammatory cytokines induced by ischemia-reperfusion injury in rats. • The niosomal form of myrtenol was more potent than the simple form in mitigating ischemia-reperfusion-induced lung injury in rats. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common cancers in men. Although many diagnostic and treatment regimens have been followed in the treatment for lung cancer, increasing mortality rate due to lung cancer is depressing and hence requires alternative plant based therapeutics with with less side‐effects. Myrtenol exhibits anti‐inflammatory and antioxidant properties. Hence we intended to study the effect of Myrtenol on B(a)P‐induced lung cancer. Our study showed that B(a)P lowered hematological count, decreased phagocyte and avidity indices, nitroblue tetrazolium (NBT) reduction, levels of immunoglubulins, antioxidant levels, whereas Myrtenol treatment restored them back to normal levels. On the other hand, xenobiotic and liver dysfunction marker enzymes and pro‐inflammatory cytokines were elevated on B(a)P exposure, which retuned back to normal by Myrtenol. This study thus describes the immunomodulatory and antioxidant effects of Myrtenol on B[a]P‐induced immune destruction. [ABSTRACT FROM AUTHOR]

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.

Background: Traumatic brain injury (TBI) is an important and growing cause of disability worldwide, and its cognitive consequences may be particularly significant. This study assessed the neuroprotective impacts of estradiol (E2), myrtenol (Myr), and the combination of the two on the neurological outcome, hemodynamic parameters, learning and memory, brain-derived neurotrophic factor (BDNF) level, phosphoinositide 3-kinases (PI3K/AKT) signaling, and inflammatory and oxidative factors in the hippocampus after TBI. Methods: Eighty-four adult male Wistar rats were randomly divided into 12 groups with seven rats in each (six groups to measure intracranial pressure, cerebral perfusion pressure, brain water content, and veterinary coma scale, and six groups for behavioral and molecular studies): sham, TBI, TBI/vehicle, TBI/Myr, TBI/E2, and TBI/Myr + E2 (Myr 50 mg/kg and E2 33.3 μg/kg via inhalation for 30 min after TBI induction). Brain injury was induced by using Marmarou's method. Briefly, a 300-g weight was dropped down from a 2-m height through a free-falling tube onto the head of the anesthetized animals. Results: Veterinary coma scale, learning and memory, brain water content, intracranial pressure, and cerebral perfusion pressure were impaired following TBI, and inflammation and oxidative stress were raised in the hippocampus after TBI. The BDNF level and PI3K/AKT signaling were impaired due to TBI. Inhalation of Myr and E2 had protective effects against all negative consequences of TBI by decreasing brain edema and the hippocampal content of inflammatory and oxidant factors and also by improving BDNF and PI3K/AKT in the hippocampus. Based on these data, there were no differences between alone and combination administrations. Conclusions: Our results propose that Myr and E2 have neuroprotective effects on cognition impairments due to TBI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

[Display omitted] A new monoterpene–azole hybrid containing myrtenyl- bispidine moiety, 2-(2,4-difluorophenyl)-1-(7-{[(1 R ,5 S)-6,6- dimethylbicyclo[3.1.1]hept-2-en-2-yl]methyl}-1,5-dimethyl- 3,7-diazabicyclo[3.3.1]non-3-yl)-3-(1 H -1,2,4-triazol-1-yl)- propan-2-ol was prepared in six steps with 55% overall yield. The compound was tested against a number of Candida spp. fungi and found to be active against Candida albicans. Molecular docking suggested possible inhibition of lanosterol 14α-demethylase (CYP51), a membrane enzyme targeted by azole antifungals. [ABSTRACT FROM AUTHOR]

Lei Liu,1,2,&ast; Bin Liu,1,2,&ast; 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&ast;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

Skin flaps are often used for repair and reconstruction, including oral cavity and palate. However, postoperative flap necrosis limited applications. Myrtenol, a plant-derived bicyclic monoterpene, has pharmacological effects including inhibiting apoptosis and promoting autophagy. But any impact on skin flaps survival remains unclear. Thus, we established modified McFarlane flaps on 24 Sprague-Dawley rats and applied myrtenol. They were randomly divided into low-dose myrtenol (L-Myr), high-dose myrtenol (H-Myr), inhibitor and control groups. On postoperative day 7, flap survival rate was increased and Laser Doppler images showed blood circulation improvement under myrtenol treatment. Hematoxylin and eosin staining (H&E) results indicated that it increased micro vessel density (MVD) and decreased neutrophil numbers. Besides, kits detection showed that it improved anti-oxidant stress factors activities and reduced pro-oxidant stress factors contents. Moreover, immunofluorescence and Western blot results demonstrated that it upregulated the expression of pro-angiogenic factors, anti-apoptotic proteins, pro-autophagic proteins, mitogen-activated protein kinase 1/2 (MEK1/2) and extracellular signal-regulated kinases 1/2 (ERK1/2) and downregulated the expression of pro-inflammatory cytokines, pro-apoptotic proteins and anti-autophagic proteins. The specific inhibitor U0126 of MEK/ERK pathway partially reversed these effects. Overall, Myrtenol promoted angiogenesis, reduced oxidative stress, ameliorated inflammation, inhibited apoptosis and upregulated autophagy via MEK/ERK pathway to promote flap survival. [Display omitted] • Myrtenol promoted skin flap survival in rats. • Myrtenol upregulated VEGF expression, thus improving blood perfusion and alleviating ischemia/reperfusion injury. • Myrtenol increased SOD activity and decreased the content of MDA to inhibit oxidative stress. • Myrtenol suppressed inflammation by diminishing the synthesis of TNF-α and IL-6. • Myrtenol inhibited apoptosis and promoted autophagy by regulating the related proteins through MEK/ERK pathway. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Asthma is related to neurochemical alterations which affect brain functions and lead to anxiety and cognitive dysfunctions. Myrtenol has sparked considerable interest due to its pharmacological effects, especially for the remediation of chronic disorders. Thus, the present research was designed to evaluate the impacts of myrtenol on anxiety-like behaviors, cognitive declines, inflammation, and oxidative stress in the hippocampus of asthmatic rats. Methods: Rats were allocated to five groups: control, asthma, asthma/vehicle, asthma/myrtenol, and asthma/budesonide. Asthma was elicited in the rats by ovalbumin, and the animals were then exposed to myrtenol inhalation. Anxiety-like behavior and memory were assessed by elevated plus maze (EPM) and novel object and location recognition tests. Interleukins (interleukin-6, -17, and -10), tumor necrosis factor α (TNF-α), and oxidative stress biomarkers such as malondialdehyde (MDA), superoxide dismutase (SOD), Glutathione peroxidase (GPX), and total antioxidant capacity (TAC) in the hippocampus were assessed by the ELISA method. Results: The levels of IL-6, IL-17, TNF-α, and MDA decreased, but GPX, SOD, and TAC levels increased in the hippocampus of asthmatic animals due to myrtenol inhalation. Conclusion: Myrtenol diminished asthma-induced anxiety-like behaviors and cognitive deficits in asthmatic rats; these effects might have been typically mediated by a reduction in inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Teucrium polium L. is a plant with various claims of ethnobotanical use, primarily for inflammatory diseases. Chemical studies have already isolated different types of terpenes from the species, and studies have established its pharmacological potential. The present study evaluates the components of T. polium essential oil cultivated in the Algerian Saharan Atlas. GC-MS identified the major components as fenchone (31.25%), 3-carene (15.77%), cis-limonene oxide (9.77%), and myrcene (9.15%). In the in silico prediction, molecules with more than 1% abundance were selected. Regarding Lipinski's rule, all molecules followed the rule. All molecules were found to be toxic in at least one model, with some molecules being non-genotoxic (6, 8, 10, 11, 12, 13) and others being non-mutagenic (5, 7, 9, 14). Three molecules were selected that showed the best results in pharmacokinetic and toxicity studies: the molecules that did not present carcinogenic potential (7-myrtenal; 9-myrtenol; 14-verbenol). The molecular target was established, and it seems that all three bound to the nuclear factor NF-kappa-B. Based on the docking and molecular dynamics results, these molecules have potential as anti-inflammatory and antitumor therapies, with further in vitro and in vivo studies needed to evaluate their activity and toxicity.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Even after one and a half years since the outbreak of COVID-19, its complete and effective control is still far from being achieved despite vaccination drives, symptomatic management with available drugs, and wider lockdowns. This has inspired researchers to screen potential phytochemicals from medicinal plants against SARS-CoV-2, adopting a bio-informatics approach. The current study aimed to assess anti-viral activity of the phytochemicals derived from Ayurvedic medicinal plants against SARS-CoV-2 drug targets [3-chymotrypsin-like protease (3CLpro) and RNA dependent RNA polymerase (RdRp)] using validated in silico methods.3D Structures of 196 phytochemicals from three Ayurvedic plants were retrieved from PubChem and KNApSAcK databases and screened for Absorption Distribution Metabolism Excretion and Toxicity(ADMET) to predict drug-likeness. The phytochemicals were subjected to molecular docking and only three showed promise: Acetovanillonewith a binding affinity of −4.7Kcal/ mol with RdRp and −4.1 Kcal/mol with 3CL pro; myrtenol with equivalent values of −4.3 Kcal/mol with RdRP and −3.2 Kcal/mol with 3CLpro; and nimbochalcin with equivalent values of −5.0Kcal/mol with RdRp and −4.9 Kcal/mol with 3CLpro. Molecular dynamics simulation (50ns) analysis was made of 3CLpro and RdRp using Autodock Vina 1.1.2 software and VMD software. After ADMET analysis, 78 phytochemicals were found suitable for molecular docking. Three, namely acetovanillone, myrtenol and nimbochalcin from Picrorhiza kurroa, Azadirachta indica and Cyperus rotundus,respectively,exhibited good binding affinity with 3CLproand RdRp of SARS-CoV-2. Interaction analysis, molecular dynamics simulations and MM-PBSA calculations were executed for two complexes, acetovanillone_RdRp and myrtenol_3CL pro.Acetovanillone_RdRpcomplex did not display any structural change after MD simulation as compared to myrtenol_3CL pro. The overall stability of acetovanillone_6NUR was 154.7 kJ/mol, and for myrtenol_1UJ1 90.5 kJ/mol.In silico analysis revealed that acetovanillone (Picrorhiza kurroa) and myrtenol (Cyperus rotundus) possess anti SARS-CoV-2 activity. Further studies are needed to validate their efficacy in biological models. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a special kind of diabetes that arises only during pregnancy. A woman with GDM has a higher risk of developing type-2 diabetes and other metabolic diseases. In this exploration, we intended to scrutinize the therapeutic actions of Myrtenol against the streptozotocin (STZ)-provoked GDM in rats. GDM was provoked in the pregnant rats via injecting the 1% of STZ (25 mg/kg) and then treated with the 50 mg/kg of myrtenol. The glucose level and bodyweight of animals were noted. The lipid profile, that is, total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) was determined by respective kits. The lipid peroxidation and antioxidants status were examined using assay kits. The status of proinflammatory markers was investigated by assay kits. The messenger RNA (mRNA) expressions of TLR4/MyD88/NF-κB signaling proteins were studied by reverse transcription polymerase chain reaction analysis. The hepatic and pancreatic tissues were examined microscopically. Myrtenol treatment notably decreased the status of blood glucose and lipid profile and improved the HDL in the GDM rats. The status of lipid peroxidation and inflammatory markers were substantially reduced by the myrtenol and it enhanced the antioxidants status of GDM animals. Myrtenol treatment remarkably downregulated the mRNA expressions of TLR4/MyD88/NF-κB signaling proteins. The histological findings also proved the therapeutic actions of myrtenol. Altogether, the findings of this investigation unveiled the therapeutic actions of the myrtenol against the STZ-provoked GDM in rats. Myrtenol could be a promising therapeutic agent to treat GDM in the future. [ABSTRACT FROM AUTHOR]

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.

The search for renewable fuels or components which may improve or replace fossil fuels is an important step towards a sustainable future. In particular, the pine oleoresin produced by conifer trees, which is composed by turpentine oil and non-volatile rosin, may be transformed into alternative fuels. In this work, combustion of six molecules which can be obtained from oleoresin either by distillation (i.e., α- and β-pinene) or by further oxyfunctionalization (nopol, terpineol, myrtenol, and borneol) was studied to assess the potential of pine oleoresin as raw material for biofuels. Emission indices of the main pollutants (carbon monoxide—CO, unburned hydrocarbons—UHC, and nitrogen oxides—NOx) were obtained in non-premixed co-flow laminar flames of the oleoresin-derived molecules blended with n-heptane. The main characteristics of the flames (i.e., temperature and height) were also determined. Significant increase in flame temperature and reduction in CO and UHC emissions with respect to n-heptane were observed with nopol, terpineol, and myrtenol, along an increase in NOx emissions, suggesting an improvement in combustion performance. In addition, differences in emission indices, evidenced for these molecules (even between α- and β-pinene), suggest the importance of the molecular structure in the combustion reaction. [ABSTRACT FROM AUTHOR]

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.

Introduction: Ischemia-reperfusion injury (IRI) is associated with the generation of reactive oxygen species, endothelial cell damage, increased vascular permeability, and the activation of neutrophils and cytokines. Myrtenol, a monoterpene alcohol, has been extensively studied and demonstrated to possess anti-inflammatory, antioxidant, and anti-apoptotic properties, offering protective effects against myocardial ischemia reperfusion injury. In this study, we aimed to investigate the effects of intraperitoneal injection of myrtenol on lung ischemia reperfusion injury. Methods and Materials: Wistar rats were categorized into four distinct groups for the study. These groups consisted of a sham group, a lung ischemia-reperfusion group, a vehicle+LIR group, and a myrtenol+LIR group. In the lung ischemia-reperfusion group, the rats were subjected to 60 minutes of ischemia followed by 120 minutes of reperfusion. The vehicle+LIR group received DMSO at a concentration of 0.5%. The myrtenol+LIR group received daily intraperitoneal injections of myrtenol for one week prior to lung ischemia-reperfusion. Various oxidative stress markers, namely SOD, superoxide dismutase, GPx, glutathione peroxidase, MDA, malondialdehyde, TOS, total oxidant status, and TAC, total antioxidant capacity, were evaluated, along with inflammatory factors Tumor necrosis factor alpha and Interleukin-6 (TNF-α and IL-6). Results: In the ischemia-reperfusion group, our results revealed a notable elevation in MDA, TOS, IL-6, and TNFα levels compared to the sham group, indicating increased oxidative stress and pro-inflammatory activity. Moreover, the activity of SOD, GPx and IL-10 was reduced in the ischemia-reperfusion group. However, when myrtenol was administered as a pretreatment, there was a significant reduction in the levels of pro-inflammatory cytokines and oxidative stress markers. Furthermore, myrtenol supplementation was found to enhance the production of antiinflammatory cytokines and antioxidant agents. Conclusion: Our findings highlight the remarkable protective effect of intraperitoneal injection of myrtenol against lung Ischemia reperfusion. [ABSTRACT FROM AUTHOR]

Introduction: Ischemia-reperfusion injury is directly related to forming reactive oxygen species, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and cytokines. Niosomes are nanocarriers and an essential part of drug delivery systems. We aimed to investigate the effects of myrtenol's inhaled niosomal form, compared to its simple form, on lung Ischemia-reperfusion injury. Methods and Material: Wistar rats were divided into four groups. Sham group, lung Ischemia Reperfusion (they were subjected to ischemia for 60 minutes and reperfusion for 120 minutes), Simple form of Myrtenol+LIR, Niosomal form of Myrtenol+LIR. Simple and niosomal forms of myrtenol were inhaled daily for one week prior to LIR. We evaluated oxidative stress (including Catalase, Superoxide Dismutase, Glutathione Peroxidase, Malondialdehyde, Total Oxidant Status, and Total Antioxidant Capacity), apoptosis (bcl-2-like protein 4 and B-cell lymphoma 2) and inflammation (Tumor necrosis factor alpha, Interleukin-17 and Interleukin-6) and histopathological indices (Wet/Dry weight Ratio, congestion of capillaries, neutrophil infiltration, and bleeding in the alveoli .) Results: Pretreatment with simple and niosomal forms of myrtenol significantly inhibited the histopathological indices, pro-inflammatory cytokines, Oxidative stress agents, apoptotic proteins. Furthermore, myrtenol increased Anti-inflammatory cytokines, Anti-Oxidants agents and antiapoptotic proteins. The niosomal form of myrtenol showed a more ameliorative effect than its simple form . Conclusion: The results showed the superior protective effect of the inhalation of its niosomal form against LIRI compared to its simple form. [ABSTRACT FROM AUTHOR]

Introduction: Paraquat is an herbicide causes cell damage and apoptosis in different tissues. Lungs are the primary organ affected by paraquat toxicity. Accumulation of paraquat in pulmonary alveoli, induces redox cycling and increases the production of dangerous reactive oxygen species and inflammatory factors including interleukins and TNF-α, resulting in acute lung injury, pneumonia, pulmonary injury, inflammation and fibrosis. Myrtenol is a medicinal plant which has therapeutic effects including anti-inflammatory, antioxidant and anti-mutation. Present research was designed to evaluate the effect of Myrtenol on acute lung damage caused by paraquat. Methods and Materials: In this study, male Wistar rats were divided in to four groups including control group, paraquat group and two treatment groups. Animals in paraquat group and treatment groups exposed to paraquat aerosol at doses of 54 mg/m3 every other day for sixteen days. Then treatment groups received Myrtenol at two different doses (25 and 50 mg/kg) for sixteen days via oral gavage. Lung tissue pathology alterations as well as TNF-α, IL-6 and IL-10 in animals’ serum were assessed. Results: Exposure to paraquat caused an increase in interleukins and TNF-α in animals’ serum. Pathological alterations including edema, pulmonary emphysema and bleeding in the lung tissues of exposed animals were detected. In the low dose treatment group, Myrtenol reduced the levels of TNF-α and IL-6 and increased IL-10. Also,in the low dose treatment group, the pathological changes caused by paraquat poisoning were reduced, while these changes were not significant in the treatment group with a high dose of Myrtenol. Conclusion: Results showed that Myrtenol reduced lung damage caused by paraquat by reducing inflammatory indicators, edema and lung bleeding. [ABSTRACT FROM AUTHOR]

Introduction: Asthma is a chronic allergic disease that affects a relatively significant portion of the world’s population. Niosomes are nanoparticles consisting of non-ionic surfactants that can be used for drug delivery. In this study, we assessed the anti-inflammatory, anti-oxidative, and anti-remodeling impacts of a formulated myrtenolloaded niosome in rats with allergic asthma. Methods and Materials: Forty-nine rats were divided into seven groups of control, vacant noisome (VN), Asthma, Asthma+VN, Asthma+SM (simple myrtenol), Asthma+NM (niosomal myrtenol, 8 mg/kg), and Asthma+B (budesonide, 41 μg). Niosomes were produced by a heating protocol, loaded with myrtenol, and their physicochemical features were evaluated. Ovalbumin-induced asthmatic animals were exposed to daily inhalation of a drug/vehicle for one week. Histopathology, inflammatory and oxidative stress indices in the lungs, and broncho-alveolar fluid (BALF) were assessed. Result: Myrtenol-loaded niosomes showed appropriate physicochemical properties. Airway smooth muscle thickness, inflammatory cell infiltration, goblet cell hyperplasia, NO, IL-17, and MDA levels decreased, and IL-10 and TAC levels increased in tissue and/or BALF of asthmatic treatment groups. Niosomal myrtenol showed high potency comparable to budesonide in alleviating disease parameters. Conclusion: In conclusion, inhalation of niosomal myrtenol ameliorated inflammation, oxidative stress and tissue remodeling in asthmatic animals comparable to budesonide and could be a target for the production of an antiasthmatic drug. [ABSTRACT FROM AUTHOR]

BACKGROUND: Insect pheromones and host volatiles are important for pest control due to their high efficiency and low potential for environmental pollution. The functions of myrtenol, myrtanol and myrtenal in pest–host interactions are unknown. This study aimed to determine the presence of myrtenol, myrtanol and myrtenal in newly emerged and emerged stages of Dendroctonus armandi, and in infected and healthy Pinus armandi, and to identify their roles in tree protection and pest management based on electroantennography (EAG), Y‐tube and toxicity experiments. RESULTS: Gas chromatographic and mass spectrometry (GC–MS) analyses, EAG, Y‐tube and toxicity assays revealed the following: (1) myrtenol was found in P. armandi phloem and did not exhibit significant toxicity towards D. armandi; (2) myrtanol was produced by infected P. armandi after D. armandi invasion and had significant toxicity towards D. armandi, especially females; and (3) myrtenal might represent an aggregation pheromone produced by female D. armandi to exert aggregation effects on other females, to help them overcome the resistance of P. armandi jointly and ensure a successful invasion, females remained in an aggregation state from leaving the host to mating in a new host. CONCLUSION: These findings suggest that myrtanol as a repellent has potential for the protection of P. armandi and that myrtenal could be used to trap and disorient D. armandi. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

One-pot bio-based myrtenol amination was studied in the presence of alumina supported Au, Au–Pd and Pd nanoparticles subjected to the thermal treatment under oxidizing or reducing atmosphere. Myrtenol amination with aniline was carried out under nitrogen atmosphere (9 bar) at 453 K using toluene as a solvent. The effect of the active metal along with the influence of redox pre-treatment on the catalytic behavior in the hydrogen borrowing reaction was explored. The catalyst characterization was done by transmission electron microscopy, X-ray photoelectron spectroscopy, inductively coupled plasma optical emission spectroscopy, nitrogen adsorption. The active metal and the catalysts redox pretreatment affected more noticeably selectivity to the reaction products rather than myrtenol conversion. Monometallic Au/Al2O3 catalyst promoted predominantly formation of the target secondary amine and the corresponding imine without a significant impact of the side reaction of C=C bond hydrogenation in myrtenol, whereas monometallic Pd catalyst activated C=C bond resulting in its hydrogenation. At the same time in the presence of Au–Pd simultaneous hydrogenation of both C=C and C=N bond occurred. Au–Pd catalysts activated in oxygen and hydrogen showed different catalytic activity determined by the composition of surface active sites. Monometallic gold catalyst was more effective in the hydrogen transfer in the case of substrates with competitive unsaturated functional groups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effect of Myrtenol, the active ingredient of Myrtle on the oxidant and anti-oxidant indices and cytokines in the allergic asthma. Allergic asthma was induced by ovalbumin (OVA) sensitization and inhalation in four groups of rats; Control, Asthma, Asthma + Dexamethasone and Asthma + Myrtenol. Myrtenol (50mg/kg) or Dexamethasone (2.5mg/kg) was administered intraperitoneally for 7 consecutive days after OVA inhalation. At the end, histopathological parameters, and interleukins (Interleukin-10 (IL10), Interferon gamma (IFN-γ), interleukin-1β (IL-1β), Tumor Necrosis Factor α (TNF-α)), and oxidative stress biomarkers, Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the lung and serum were measured by hematoxylin and eosin staining and ELISA method, respectively. Myrtenol reduced the pathological changes in the lungs and airway endothelium (P < 0.01), (P < 0.5). The level of IL-1β (P < 0.05) and MDA in the serum and lung tissue (P < 0.01), (P < 0.05), and also the level of TNF-α (P < 0.05) in the lung tissue decreased in the Myrtenol group compared to the asthma group. Myrtenol increased the level of IL-10 (P < 0.05) and the activity of GPX in the lung tissue and serum (P < 0.001). Myrtenol may improve asthma by increasing the ratio of antioxidants to oxidants and reducing the ratio of pro-inflammatory to anti-inflammatory interleukins in the lung. Myrtenol is presented as a potent herbal medicine ingredient for the treatment of asthma. [ABSTRACT FROM AUTHOR]

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.

Graphical abstract Highlights: • The microwave spectrum of myrtenol has been observed for the first time. • Three conformers have been observed and assigned from the spectrum. • Highly accurate rotational constants were obtained for each of the conformers. • DFT calculations were found to better predict the experimentally observed constants. • The energetic progression inferred from the spectrum matches theory. Abstract The microwave spectrum of the chiral monoterpenol molecule, (1R)-(−)-myrtenol, has been observed using CP-FTMW spectroscopy in the 6–18 GHz region of the electromagnetic spectrum. Transitions linked to three conformers of the primary alcohol group were experimentally observed, while no conformers associated with changes to the bicyclic cage were detected. The most numerous and intense transitions correspond with the global minimum structure predicted by both Density Functional Theory (DFT) and ab initio calculations. The second moments of inertia predicted by DFT were found to agree very well with those determined experimentally for all three conformers. However, an empirical correction for dispersion was required for the DFT calculations before the energetic ordering of the conformers matched those predicted by ab initio calculations. This also placed the ordering in agreement with that suggested by the experimental spectrum. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hydroformylation of myrtenol and nopol was performed in eco-friendly solvents. • Both substrates revealed to be quite reluctant to hydroformylation. • Both substrates showed a strong tendency to form isomeric saturated aldehydes. • In spite of this challenge, fragrance aldehydes were obtained in good yields. • The reaction mechanism is discussed. The hydroformylation of the naturally occurring hydroxyolefins (1R)-(–)-myrtenol (1) and (1R)-(–)-nopol (2) was performed employing a rhodium(I)/bulky phosphite catalytic system. Both substrates demonstrated to be quite reluctant to hydroformylation and revealed a strong tendency to form isomeric saturated aldehydes under hydroformylation conditions. In spite of these challenges, catalytic systems and conditions were found to allow the synthesis of corresponding hydroxyaldehydes. The products, either isolated or as a mixture, presented a pleasant smell and are potentially useful as fragrances. In addition, it was possible to perform the reactions in eco-friendly solvents. [ABSTRACT FROM AUTHOR]

Methyl pheophorbide a reacts with terpene alcohols on activation with the Mukaiyama reagent to give the products of the formal transesterification of the C(21)CO2Me group. To increase hydrophilicity, the synthesized conjugates were modified following two different paths. The first path is the acid-catalyzed transesterification of the C(3)(CH2)2CO2Me moiety of the conjugate with triethylene glycol to give diester with different substituents and different ester groups. The second path is the treatment of terpenyl ester with N,N-dimethylethylenediamine that proceeds via the phorbin exocycle opening to give the porphine derivatives bearing two ester and one carboxamide groups. The dimethylamino groups of these porphine derivatives were quaternized with iodomethane. [ABSTRACT FROM AUTHOR]

GABAA receptors are ligand-gated anion channels that form pentameric arrangements of various subunits. Positive allosteric modulators of GABAA receptors have been reported as being isolated either from plants or synthesized analogs of known GABAA receptor targeting drugs. Recently, we identified monoterpenes, e.g. myrtenol as a positive allosteric modulator at α1β2 GABAA receptors. Here, along with pharmacophore-based virtual screening studies, we demonstrate that scaffold modifications of myrtenol resulted in the loss of modulatory activity. Two independent approaches, fluorescence-based compound analysis and electrophysiological recordings in whole-cell configurations were used for analysis of transfected cells. C-atoms 1 and 2 of the myrtenol backbone were identified as crucial to preserve positive allosteric potential. A modification at C-atom 2 and lack of the hydroxyl group at C-atom 1 exhibited significantly reduced GABAergic currents at α1β2, α1β2γ, α2β3, α2β3γ and α4β3δ receptors. This effect was independent of the γ2 subunit. A sub-screen with side chain length and volume differences at the C-atom 1 identified two compounds that inhibited GABAergic responses but without receptor subtype specificity. Our combined approach of pharmacophore-based virtual screening and functional readouts reveals that side chain modifications of the bridged six-membered ring structure of myrtenol are crucial for its modulatory potential at GABAA receptors. [ABSTRACT FROM AUTHOR]

Myrtenol is a monoterpene with multiple pharmacological activities. However, although monoterpenes have been proposed to play beneficial roles in a variety of cardiac disorders, pharmacological actions of myrtenol in the heart are not yet reported. Hence, the aim of this study was to evaluate whether myrtenol promotes cardioprotection against myocardial ischemia-reperfusion (IR) injury, and the mechanisms involved in these effects. Male Wistar rats were orally treated for seven consecutive days with myrtenol (50 mg/kg) or N-acetyl cysteine (1.200 mg/kg, NAC). Afterward, hearts were subjected to myocardial IR injury. Here, we show that the severe impairment of contractile performance induced by IR was significantly prevented by myrtenol or NAC. Moreover, myrtenol abolished aberrant electrocardiographic waveform (ST-segment elevation), as well as reduced life-threatening arrhythmias and infarct size induced by IR injury. Importantly, myrtenol fully prevented the massive increase of cardiac reactive oxygen species generation and oxidative stress damage. Accordingly, myrtenol restored the impairment of endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and reductase) activities and balance of pro- and anti-apoptotic pathways (Bax and Bcl-2), associated with decreased apoptotic cells. Taken together, our data show that myrtenol promotes cardioprotection against IR injury through attenuation of oxidative stress and inhibition of pro-apoptotic pathway. [ABSTRACT FROM AUTHOR]