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Nature Communications Jul 2020Menthol in mints elicits coolness sensation by selectively activating TRPM8 channel. Although structures of TRPM8 were determined in the apo and liganded states, the...
Menthol in mints elicits coolness sensation by selectively activating TRPM8 channel. Although structures of TRPM8 were determined in the apo and liganded states, the menthol-bounded state is unresolved. To understand how menthol activates the channel, we docked menthol to the channel and systematically validated our menthol binding models with thermodynamic mutant cycle analysis. We observed that menthol uses its hydroxyl group as a hand to specifically grab with R842, and its isopropyl group as legs to stand on I846 and L843. By imaging with fluorescent unnatural amino acid, we found that menthol binding induces wide-spread conformational rearrangements within the transmembrane domains. By Φ analysis based on single-channel recordings, we observed a temporal sequence of conformational changes in the S6 bundle crossing and the selectivity filter leading to channel activation. Therefore, our study suggested a 'grab and stand' mechanism of menthol binding and how menthol activates TRPM8 at the atomic level.
Topics: Binding Sites; HEK293 Cells; Humans; Ion Channel Gating; Menthol; Molecular Docking Simulation; Molecular Dynamics Simulation; Mutagenesis; Patch-Clamp Techniques; Point Mutation; Protein Binding; Recombinant Proteins; Structure-Activity Relationship; TRPM Cation Channels
PubMed: 32728032
DOI: 10.1038/s41467-020-17582-x -
Menthol-based deep eutectic systems as antimicrobial and anti-inflammatory agents for wound healing.European Journal of Pharmaceutical... Mar 2023Effective antimicrobial treatment has been identified as a serious and unmet medical need. Herein, we present a strategy based on deep eutectic systems (DES) to overcome...
Effective antimicrobial treatment has been identified as a serious and unmet medical need. Herein, we present a strategy based on deep eutectic systems (DES) to overcome current limitations, answering the need not only to effectively kill bacterial agents but also to avoid their adhesion and proliferation, which is associated with biofilm formation and have a crucial impact on bacterial virulence. To achieve such a goal, natural deep eutectic systems (NADES) based on menthol (Me) and saturated free fatty acids (FFA) were produced, fully physicochemical characterized, and its bioactive properties were described. The antimicrobial potential of menthol-based NADES with FFA, namely, myristic acid (MA), lauric acid (LA), and stearic acid (SA) were investigated towards a broad panel of microorganisms. The obtained data indicates that NADES possess effective antimicrobial properties towards the Gram-positive bacterial and fungal strains tested. Among the tested formulations, Me:LA at a molar ratio of 4:1 molar was used to carry out a biofilm detachment/removal assay due to is superior microbiological properties. This formulation was able to effectively lead to biofilm removal/dispersion of not only methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans, but also Escherichia coli, without the need of any additional physical force or antibiotic. Furthermore, since microbial invasion and biofilm formation is highly undesired in wound healing, namely in chronic wound healing, the wound healing properties of these eutectic formulations was also investigated. The results suggest that these NADES can cope with microbial invasion and biofilm detachment while not compromising normal keratinocyte proliferation and migration verified in wound healing and epidermis repair, while also contributing to the reduction of cell stress and inflammation via the control of ROS production. In conclusion, these results provide the indication that NADES based on Me and FFA holds great interest as antimicrobial agents for preventive and therapeutic applications in various clinical settings, including wound healing.
Topics: Menthol; Methicillin-Resistant Staphylococcus aureus; Anti-Infective Agents; Anti-Bacterial Agents; Anti-Inflammatory Agents; Wound Healing
PubMed: 36572356
DOI: 10.1016/j.ejps.2022.106368 -
Journal of the American Board of Family... 2018Over-the-counter (OTC) cough remedies are lightly regulated and their potential side effects may go unrecognized. During 2015, over 282 million cough drops were sold in... (Observational Study)
Observational Study
BACKGROUND
Over-the-counter (OTC) cough remedies are lightly regulated and their potential side effects may go unrecognized. During 2015, over 282 million cough drops were sold in the United States. A Wisconsin community clinician (RM) made clinical observations suggesting that excessive use of OTC cough drops may exacerbate rather than benefit coughs. The goal of this project was to assess whether menthol in cough drops is related to worse cough symptoms.
METHODS
From April 2016 through May 2017, 5 Wisconsin primary care clinics invited adolescent and adult outpatients seeking medical care for an acute or subacute cough to take a voluntary, anonymous, 10-question cough drop use survey that included age, sex, smoking status, cough severity, cough duration, and cough drop use (including type and amount).
RESULTS
Of the 548 surveys collected and analyzed, 363 (66.2%) reported using cough drops. Cough drop use was significantly associated with longer duration of cough at presentation ( < .001) but not with overall cough severity ( = .09). Of cough drop users, 269 (90%) reported consuming drops with menthol. Univariate analysis found no statistically significant differences between the menthol and nonmenthol groups for either severity ( = .65) or duration ( = .17). However, significant independent associations were found between cough severity and 1) average menthol dose per cough drop (R = 0.19; = .007), 2) number of cough drops consumed daily (R = 0.2; = .002) and 3) total amount of menthol consumed per day (R = 0.21; = .001) that remained significant ( = .003) after controlling for age, sex, smoking status, season, and clinic site.
CONCLUSIONS
Cough severity in some individuals may be negatively influenced by the amount of menthol consumed via cough drops. Clinicians should include cough drop use in history taking of patients with persisting cough illnesses. Further research into potential mechanisms is warranted.
Topics: Adult; Aged; Cough; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Humans; Male; Menthol; Middle Aged; Nonprescription Drugs; Primary Health Care; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Wisconsin
PubMed: 29535234
DOI: 10.3122/jabfm.2018.02.170363 -
Molecules (Basel, Switzerland) Jul 2023infections are highly common amongst the global population. Such infections have been shown to be the cause of gastric ulcers and stomach carcinoma and, unfortunately,...
infections are highly common amongst the global population. Such infections have been shown to be the cause of gastric ulcers and stomach carcinoma and, unfortunately, most cases are asymptomatic. Standard treatment requires antibiotics such as metronidazole or azithromycin to which many strains are now resistant. species have been used as a natural treatment for gastrointestinal diseases throughout history and essential oils (EOs) derived from these plants show promising results as potential antimicrobial agents. In this study, EOs obtained from the leaves and flowers of five cultivars of × and were examined by GC-MS. The investigated mints are representatives of four chemotypes: the menthol chemotype ( × 'Multimentha' and × 'Swiss'), the piperitenone oxide chemotype ( × 'Almira'), the linalool chemotype ( × 'Granada'), and the carvone chemotype ( 'Moroccan'). The chemical composition of EOs from mint flowers and leaves was comparable with the exception of the Swiss cultivar. Menthol was the most abundant component in the leaves while menthone was highest in flowers. The ATCC 43504 reference strain and 10 other clinical strains were examined for their sensitivity to the EOs in addition to their major monoterpenoid components (menthol, menthone, carvone, dihydrocarvone, linalool, 1,8-cineole, and limonene). All tested mint EOs showed inhibitory activity against both the reference ATCC 43504 strain (MIC 15.6-31.3 mg/L) and clinical strains (MIC 31.3-250 mg/L/62.5-500 mg/L). Among the reference monoterpenes, menthol (MIC 7.8/31.3 mg/L) and carvone (MIC 31.3/62.5 mg/L) had the highest anti- activity, which also correlated with a higher activity of EOs containing these compounds ( × 'Swiss' and 'Moroccan'). A synergistic and additive interaction between the most active EOs/compounds and antibiotics possibly points to a new plant-based anti- treatment.
Topics: Humans; Oils, Volatile; Menthol; Mentha; Helicobacter pylori; Helicobacter Infections; Mentha piperita; Anti-Bacterial Agents
PubMed: 37570659
DOI: 10.3390/molecules28155690 -
Substance Abuse Treatment, Prevention,... Aug 2021The potential impact of menthol versus non-menthol cigarette use on smoking behaviors is an intensely scrutinized topic in the public health arena. To date, several... (Meta-Analysis)
Meta-Analysis Review
Assessing the evidence on the differential impact of menthol versus non-menthol cigarette use on smoking cessation in the U.S. population: a systematic review and meta-analysis.
BACKGROUND
The potential impact of menthol versus non-menthol cigarette use on smoking behaviors is an intensely scrutinized topic in the public health arena. To date, several general literature reviews have been conducted, but findings and conclusions have been discordant. This systematic review followed PRISMA guidelines to examine the Key Question, "Does menthol cigarette use have a differential impact on smoking cessation compared with non-menthol cigarette use?"
METHODS
Six databases-Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, MEDLINE, Embase and PsycInfo-were queried from inception to June 12, 2020. Articles comparing menthol versus non-menthol cigarette smokers in terms of at least one predefined smoking cessation outcome were included. Risk of bias was assessed using the Agency for Healthcare Research and Quality Evidence-Based Practice Center approach. A random-effects model utilizing the DerSimonian and Laird method to pool adjusted odds ratio was applied. Variations among pooled studies were assessed using Cochran's Q statistic, and heterogeneity was quantified using the inconsistency index (I).
RESULTS
Forty-three demographically adjusted studies (22 rated "good", 20 rated "fair", and one study rated "poor" individual study quality) comparing menthol and non-menthol smokers were qualitatively synthesized across the following measures (study count; strength of evidence): duration of abstinence (2; low); quit attempts (15; insufficient); rate of abstinence/quitting (29; moderate); change in smoking quantity/frequency (5; insufficient); and, return to smoking/relapse (2; insufficient). Overall, the qualitative synthesis failed to show a consistent trend for an association between menthol cigarette use and smoking cessation across outcomes. Meta-analyses found no difference between menthol and non-menthol cigarette use and either quit attempts or abstinence.
CONCLUSIONS
Given the lack of consistency or statistical significance in the findings-combined with a "low" overall strength of evidence grade, based on deficiencies of indirectness and inconsistency-no consistent or significant associations between menthol cigarette use and smoking cessation were identified. Recommendations for future studies include increased focus on providing longitudinal, adjusted data collected from standardized outcome measures of cessation to better inform long-term smoking cessation and menthol cigarette use. Such improvements should also be further considered in more methodologically rigorous systematic reviews characterized by objectivity, comprehensiveness, and transparency with the ultimate objective of better informing public health and policy decision making.
Topics: Humans; Menthol; Smoking; Smoking Cessation; Tobacco Products; Tobacco Use Cessation Devices; United States
PubMed: 34380503
DOI: 10.1186/s13011-021-00397-4 -
Nicotine & Tobacco Research : Official... Oct 2021Cigarette smoking is disproportionately common among sexual minorities. While menthol market share has increased in the past decade, research on menthol cigarette...
INTRODUCTION
Cigarette smoking is disproportionately common among sexual minorities. While menthol market share has increased in the past decade, research on menthol cigarette smoking among sexual minorities is scant. For this study, we examined menthol cigarette smoking in the United States, by sex and sexual identity using a nationally representative sample of adults.
AIMS AND METHODS
We pooled data from the 2015-2019 National Survey on Drug Use and Health. We used chi-square tests and multivariable logistic regression models to examine (1) past 30-day cigarette use, (2) past 30-day menthol use, and (3) menthol preference among adults who have smoked cigarettes in the past 30 days for the following groups: heterosexual/straight males, heterosexual/straight females, gay males, gay/lesbian females, bisexual males, and bisexual females. Data were analyzed in September 2020.
RESULTS
Bivariate analyses revealed that prevalence of cigarette smoking and menthol cigarette smoking were higher among sexual minorities compared with heterosexual respondents, and that preference for menthol was highest among lesbian/gay and bisexual females who smoke. Multivariable models showed that compared with heterosexual females who smoke, odds of menthol preference were lower among heterosexual/straight and bisexual males who smoke, and higher among bisexual females.
CONCLUSIONS
Our study found that menthol preference was disproportionately high among sexual minorities who smoke-bisexual and gay/lesbian females who smoke in particular. Research is needed to understand why menthol use is common among sexual minorities who smoke.
IMPLICATIONS
Using data from a nationally representative study, this study makes a unique contribution to literature by identifying differences in menthol smoking between sexual minority subgroups. Specifically, we found that menthol smoking was highest among sexual minority females (ie, lesbian/gay and bisexual females) compared with other sexual minorities. These findings highlight the need for targeted interventions to prevent menthol cigarette initiation among sexual minorities, as well as to promote smoking cessation among sexual minorities who smoke menthol cigarettes, with an emphasis on sexual minority females. Future research should examine the impact of a potential menthol ban on these inequalities.
Topics: Adult; Cigarette Smoking; Female; Humans; Male; Menthol; Sexual and Gender Minorities; Smoke; Tobacco Use; United States
PubMed: 34255831
DOI: 10.1093/ntr/ntab101 -
Nicotine & Tobacco Research : Official... Mar 2023The purpose of this study was to determine the effects of smoking and other outcomes of assigning cigarettes with reduced nicotine and/or no menthol to female menthol... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The purpose of this study was to determine the effects of smoking and other outcomes of assigning cigarettes with reduced nicotine and/or no menthol to female menthol smokers.
AIMS AND METHODS
Nontreatment-seeking female menthol smokers (N = 263) participated in a randomized controlled trial in which levels of menthol and nicotine in cigarettes were manipulated using experimental cigarettes. After a baseline period, participants were assigned to the following conditions for 6 weeks: (1) their own brand of cigarette (conventional nicotine with menthol), (2) a conventional nicotine cigarette with no menthol, (3) a cigarette with reduced nicotine (RNC) with menthol, or (4) a RNC cigarette and no menthol. Participants then returned to using their own brand and were followed for another 6 weeks. Outcomes included cigarettes smoked, biomarkers of exposure, and dependence measures.
RESULTS
Results indicated that, after an initial increase, rates of smoking of all three experimental cigarettes were at or below baseline rates of smoking of one's own brand. Levels of biomarkers also decreased during the experimental phase but rebounded somewhat after participants resumed smoking their own brand. There was evidence that the overall amount of smoking decreased similarly among women who switched to non-menthol and/or RNC cigarettes.
CONCLUSIONS
These results suggest that no detrimental effect will occur in nicotine or toxicant exposure levels with a ban on characterizing menthol and/or a product standard on nicotine content in cigarettes.
IMPLICATIONS
The implication of this work is that there would be no risk to women menthol smokers associated with regulations restricting nicotine and eliminating menthol in cigarettes.
Topics: Female; Humans; Nicotine; Smoking; Smokers; Menthol; Tobacco Products; Biomarkers
PubMed: 36156108
DOI: 10.1093/ntr/ntac225 -
Journal of Neurophysiology Feb 2022Unmyelinated tactile (C-tactile or CT) afferents are abundant in arm hairy skin and have been suggested to signal features of social affective touch. Here, we recorded...
Unmyelinated tactile (C-tactile or CT) afferents are abundant in arm hairy skin and have been suggested to signal features of social affective touch. Here, we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves. The most distal receptive fields were located on the proximal phalanx of the third finger for the superficial branch of the radial nerve and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial ( = 27), radial ( = 8), and peroneal ( = 4) nerves. Moreover, we found that although CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared with C-nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch. Unmyelinated tactile (CT) afferents are abundant in arm hairy skin and are thought to signal features of social affective touch. We show that CTs are also present but are relatively sparse in the lower leg compared with C-nociceptors. CTs display similar physiological properties across the arm and leg nerves. Furthermore, CT afferents do not respond to the cooling agent menthol or the pruritogen histamine, and their mechanical response properties are not altered by these chemicals.
Topics: Adult; Affect; Afferent Pathways; Antipruritics; Female; Histamine; Histamine Agonists; Humans; Leg; Male; Mechanoreceptors; Menthol; Nerve Fibers, Unmyelinated; Nociceptors; Peroneal Nerve; Radial Nerve; Touch Perception; Young Adult
PubMed: 35020516
DOI: 10.1152/jn.00310.2021 -
Nicotine & Tobacco Research : Official... Oct 2020Youth cigarette smoking decreased significantly over the last two decades in the United States. This study provides estimates and trends from 2011 to 2018 and factors...
INTRODUCTION
Youth cigarette smoking decreased significantly over the last two decades in the United States. This study provides estimates and trends from 2011 to 2018 and factors associated with youth menthol and non-menthol smoking from 2016 to 2018.
METHODS
Using data from the 2011-2018 National Youth Tobacco Surveys, past 30-day (current) menthol and non-menthol cigarette smoking were estimated for all youth (prevalence) and youth smokers (proportions). Trends were examined using Joinpoint regression, calculating the annual percent change (APC). Multivariate logistic regression analyses identified factors associated with menthol smoking.
RESULTS
From 2011 to 2018, menthol cigarette smoking among current youth cigarette smokers significantly decreased from 57.3% to 45.7% (APC: -3.0%), while non-menthol (38.2% to 47.3% [APC: 2.9%]) and unknown menthol status (not sure\missing) (4.5% to 7.0% [APC: 7.1%]) significantly increased. Menthol cigarette smoking among high school, male, female, and non-Hispanic white current cigarette smokers decreased, but remained unchanged among middle school, non-Hispanic black, and Hispanic smokers. Significantly higher proportions of menthol cigarette smokers smoked on ≥20 days, ≥2 cigarettes per day, and ≥100 cigarettes in their lifetime compared to non-menthol smokers. Among current cigarette smokers, non-Hispanic blacks, Hispanics, flavored non-cigarette tobacco users, frequent smokers (≥20 days), those smoking 2-5 cigarettes per day, and those living with someone who uses tobacco had higher odds of menthol cigarette smoking.
CONCLUSIONS
In 2018, nearly half of current youth cigarette smokers smoked menthol cigarettes. While menthol cigarette smoking declined from 2011 to 2018 among all youth and among youth smokers, there was no change in menthol cigarette smoking among non-Hispanic black, Hispanic, and middle school cigarette smokers.
IMPLICATIONS
This study finds that overall cigarette and menthol cigarette smoking declined in youth from 2011 to 2018. However, menthol cigarette smoking among non-Hispanic black, Hispanic, and middle school youth cigarette smokers did not change. Information from this study can help inform efforts to reduce menthol cigarette smoking among US youth, particularly racial/ethnic minority populations.
Topics: Adolescent; Child; Cigarette Smoking; Ethnicity; Female; Humans; Male; Menthol; Prevalence; Schools; Smokers; Smoking Cessation; Students; Surveys and Questionnaires; United States
PubMed: 32347935
DOI: 10.1093/ntr/ntaa054 -
International Journal of Molecular... Jan 2023Flavorings enhance the palatability of e-cigarettes (e-cigs), with menthol remaining a popular choice among e-cig users. Menthol flavor remains one of the only flavors...
Flavorings enhance the palatability of e-cigarettes (e-cigs), with menthol remaining a popular choice among e-cig users. Menthol flavor remains one of the only flavors approved by the United States FDA for use in commercially available, pod-based e-cigs. However, the safety of inhaled menthol at the high concentrations used in e-cigs remains unclear. Here, we tested the effects of menthol on parameters of mucociliary clearance (MCC) in air-liquid interface (ALI) cultures of primary airway epithelial cells. ALI cultures treated with basolateral menthol (1 mM) showed a significant decrease in ciliary beat frequency (CBF) and airway surface liquid (ASL) volumes after 24 h. Menthol nebulized onto the surface of ALI cultures similarly reduced CBF and increased mucus concentrations, resulting in decreased rates of mucociliary transport. Nebulized menthol further increased the expression of mucin 5AC (MUC5AC) and mRNA expression of the inflammatory cytokines and . Menthol activated TRPM8, and the effects of menthol on MCC and inflammation could be blocked by a specific TRPM8 antagonist. These data provide further evidence that menthol at the concentrations used in e-cigs could cause harm to the airways.
Topics: Mucociliary Clearance; Menthol; Mucin 5AC; Electronic Nicotine Delivery Systems; Epithelial Cells
PubMed: 36675209
DOI: 10.3390/ijms24021694