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Journal of Leukocyte Biology Sep 2022Understanding the innate immune system and how aberrant activation or impaired inhibition leads to the development of hyperinflammatory conditions, including...
Understanding the innate immune system and how aberrant activation or impaired inhibition leads to the development of hyperinflammatory conditions, including inflammatory bowel disease, is crucial for patient management and treatment. An emerging area of interest surrounding dysregulated inflammation focuses on membrane bound transient receptor potential (TRP) ion channels. These channels are permeable to calcium and other cations involved in the balance of leukocyte membrane potential and function, as well as afferent neuron signaling within the myenteric plexus of the GI tract, bladder, and skin. A particular channel, TRPM8, is an important cell surface marker for prostate cancer and participates in the function of cold sensing neurons. Specifically, this ion-gated receptor is shown to be activated by agonists such as menthol and eucalyptus, which aid in the soothing, cooling effects of these agents. Furthermore, the TRPM8 channel is also identified on the surface of resident tissue Mϕs and is also linked to the protective role and release of calcitonin gene-related peptide (CGRP) by sensory neurons.
Topics: Calcium Signaling; Cold Temperature; Humans; Menthol; Monocytes; TRPM Cation Channels
PubMed: 35570407
DOI: 10.1002/JLB.3CE0222-099R -
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 -
Phytochemistry Nov 2022Plant monoterpenes are challenging compounds, since they often act as solvents, and thus have both phytotoxic and antimicrobial properties. In this study an approach is...
Plant monoterpenes are challenging compounds, since they often act as solvents, and thus have both phytotoxic and antimicrobial properties. In this study an approach is developed to identify and characterize enzymes that can detoxify monoterpenoids, and thus would protect both plants and microbial production systems from these compounds. Plants respond to the presence of monoterpenes by expressing glycosyltransferases (UGTs), which conjugate the monoterpenoids into glycosides. By identifying these enzymes in a transcriptomics approach using Mentha × piperita, a family of UGTs was identified which is active on cyclic monoterpenoids such as menthol, and on acyclic monoterpenoids such as geranic acid. Other members of this family, from tomato, were also shown to be active on these monoterpenoids. In vitro and in vivo activity of different UGTs were tested with different substrates. We found that some glycosyltransferases significantly affect the toxicity of selected monoterpenoids in Escherichia coli, suggesting that glycosyltransferases can protect cells from monoterpenoid toxicity.
Topics: Glycosides; Glycosyltransferases; Mentha piperita; Menthol; Monoterpenes; Solvents
PubMed: 36037906
DOI: 10.1016/j.phytochem.2022.113371 -
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 Studies on Alcohol and Drugs Mar 2023Rates of e-cigarette use among adolescents and young adults (AYAs) remain high despite several federal policy changes intended to limit their availability and appeal....
OBJECTIVE
Rates of e-cigarette use among adolescents and young adults (AYAs) remain high despite several federal policy changes intended to limit their availability and appeal. The current study examined how restricting flavors would affect current AYA users' intentions to discontinue vaping, as a function of their current flavor preference.
METHOD
In a national cross-sectional survey, AYA e-cigarette users ( = 1,414) completed measures of e-cigarette use, device type, e-liquid flavor (tobacco, menthol, cool mint, fruit ice, fruit/sweet), and intent to discontinue e-cigarette use in response to hypothetical federal product standards (i.e., tobacco and menthol or tobacco-only e-liquid). Logistic regression was used to model the association of preferred flavor with odds of discontinuing e-cigarette use (vs. continuing), for menthol and tobacco hypothetical product standards.
RESULTS
Overall, 38.8% of the sample reported intent to discontinue using their e-cigarette if tobacco and menthol-flavored e-liquid were the only options available, whereas 70.8% would discontinue under a tobacco-only product standard. AYAs preferring fruit/sweet flavor were most sensitive to either restricted scenario, with odds of discontinuing use ranging from adjusted odds ratio (aOR) = 2.22 to aOR = 2.38 under a tobacco and menthol product standard and aOR = 1.33 to aOR = 2.59 under a tobacco-only product standard, compared with other flavor preferences. In addition, AYAs using cooling flavors (e.g., fruit ice) reported higher odds of discontinuing use under a tobacco-only product standard, compared with menthol flavor users, indicating an important distinction between these groups.
CONCLUSIONS
Results indicate potential for flavor restrictions to reduce use of e-cigarettes among AYAs and suggest that a tobacco flavor product standard may result in the greatest discontinuation of use.
Topics: Humans; Young Adult; Adolescent; Electronic Nicotine Delivery Systems; Cross-Sectional Studies; Ice; Menthol; Tobacco Products
PubMed: 36971721
DOI: 10.15288/jsad.21-00466 -
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 -
BMC Public Health Sep 2022Flavored tobacco products are highly appealing to youth. The Federal government lacks a comprehensive flavored tobacco products policy and states have adopted different...
BACKGROUND
Flavored tobacco products are highly appealing to youth. The Federal government lacks a comprehensive flavored tobacco products policy and states have adopted different approaches restricting these products. This study analyzes the impact of Massachusetts' comprehensive prohibition and New Jersey's partial restriction on the sale of flavored tobacco products.
METHODS
NielsenIQ Retail Scanner data were used to construct four log per capita dependent variables: e-liquid milliliters, cigarette packs, cigars, and smokeless tobacco ounces for products flavored as fruit, menthol, mint, tobacco and other. All models used difference-in-differences regressions, with Virginia and Pennsylvania serving as controls. The models controlled for state level product prices, population percentages by race/ethnicity, proportion male, median household income, unemployment rate, minimum legal sales age, tobacco 21 policies, and cumulative cases and deaths of COVID-19; the models accounted for time-specific factors by using 4-week period fixed-effects.
RESULTS
There was a significant decrease in sales across all flavored tobacco products in Massachusetts, including fruit [-99.83%, p < 0.01], menthol [-98.33%, p < 0.01], and all other flavored [-99.28%, p < 0.01] e-cigarettes. The cigar group "all other-flavors" [-99.92%, p < 0.01] and menthol flavored cigarettes [-95.36%, p < 0.01] also significantly decreased. In New Jersey, there was a significant decrease in per capita sales of menthol-flavored e-cigarettes [-83.80%, p < 0.05] and cigar group "all other-flavors" experienced a significant increase in per capita sales [380.66%, p < 0.01].
CONCLUSIONS
This study contributes to the growing body of evidence demonstrating the impact of sales prohibitions on reducing sales of flavored tobacco products. Statewide comprehensive approaches appear more effective than partial restrictions and should be prioritized.
IMPLICATIONS
Results from this study support emerging research that demonstrates the promising effects of comprehensive flavoring sales prohibitions. This study can be used to inform future flavored tobacco product policy solutions developed by advocates and policy makers to curb overall tobacco initiation and use by youth and adults.
Topics: Adolescent; Adult; COVID-19; Electronic Nicotine Delivery Systems; Flavoring Agents; Humans; Male; Menthol; Tobacco Products
PubMed: 36138373
DOI: 10.1186/s12889-022-14172-y -
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 -
Tobacco Control Nov 2023Menthol masks the harshness of cigarette smoke, promotes youth smoking and encourages health-concerned smokers who incorrectly believe that menthols are less harmful to...
BACKGROUND
Menthol masks the harshness of cigarette smoke, promotes youth smoking and encourages health-concerned smokers who incorrectly believe that menthols are less harmful to smoke menthols. This study of smokers in Kenya and Zambia is the first study in Africa to examine menthol use, smokers' beliefs about its harmfulness and the factors associated with menthols.
METHODS
Data were from the International Tobacco Control (ITC) Kenya Wave 2 (2018) and Zambia Wave 2 Survey (2014), involving nationally representative samples of smokers. This study focuses on 1246 adult smokers (644 in Kenya, 602 in Zambia) who reported smoking a usual brand of cigarettes (menthol or non-menthol).
RESULTS
Overall, menthol use was significantly higher among smokers in Zambia than in Kenya (48.0% vs 19.0%), females (45.6% vs 31.2% males), non-daily smokers (43.8% vs 30.0% daily) and those who exclusively smoked factory-made (FM) cigarettes (43.0% vs 15.2%). The erroneous belief that menthols are less harmful was more likely among smokers in Zambia than in Kenya (53.4% vs 29.3%) and among female smokers (38.5% vs 28.2%). In Kenya, menthol smoking was associated with being female (adjusted odds ratios (AOR)=3.07; p=0.03), worrying about future health (AOR=2.28; p=0.02) and disagreeing with the statement that smoking was calming (AOR=2.05; p=0.04). In Zambia, menthol use was associated with being female (AOR=3.91; p=0.002), completing primary school (AOR=2.14; p=0.03), being a non-daily smoker (AOR=2.29; p=0.03), exclusively using FM cigarettes (AOR=14.7; p<0.001), having a past quit attempt (AOR=1.54; p=0.02), believing that menthols are less harmful (AOR=3.80; p<0.001) and choosing menthols because they believed it was less harmful (AOR=3.52; p<0.001).
CONCLUSIONS
Menthols are highly prevalent among females in both countries. There is a need in African countries to combat the myth that menthols are less harmful and to ban menthol and other flavourings.
Topics: Adult; Male; Adolescent; Humans; Female; Cigarette Smoking; Menthol; Zambia; Kenya; Prevalence; Nicotiana; Tobacco Products
PubMed: 35459749
DOI: 10.1136/tobaccocontrol-2021-057100 -
The Journal of Adolescent Health :... Jun 2022Minneapolis and St. Paul, Minnesota, implemented sales restrictions on all flavored tobacco products in 2016 ("flavor policy") and expanded the restrictions to menthol...
PURPOSE
Minneapolis and St. Paul, Minnesota, implemented sales restrictions on all flavored tobacco products in 2016 ("flavor policy") and expanded the restrictions to menthol tobacco products in 2018 ("menthol policy"). We examined data from surveys of Minnesota youth collected before and after the flavor and menthol policies.
METHODS
We measured changes in youth tobacco use prevalence using data from the Minnesota Youth Tobacco Survey and the Minnesota Student Survey. We analyzed tobacco use overall and, where possible, by product category and flavor category among survey respondents in the Twin Cities area (including Minneapolis and St. Paul) and the rest of the state of Minnesota (ROS).
RESULTS
In the Minnesota Youth Tobacco Survey, overall youth use of any tobacco product significantly increased in ROS (by 26.6%) but did not change in the Twin Cities after the flavor policies. Similarly, the Minnesota Student Survey showed the youth use of any tobacco product increased to a greater extent in ROS (by 44.6%) than that in the Twin Cities (by 34.6%) after implementation of the menthol policies. In both surveys, increases in youth use of particular tobacco products were less pronounced in the Twin Cities relative to the rest of the state.
DISCUSSION
Policies restricting sales of all flavored and menthol tobacco products may be associated with attenuated increases in youth use of tobacco product categories. Policy exemptions and proximity to nonpolicy jurisdictions may have diluted the effect of policies on overall tobacco product use among youth tobacco users.
Topics: Adolescent; Electronic Nicotine Delivery Systems; Flavoring Agents; Humans; Menthol; Minnesota; Reactive Oxygen Species; Nicotiana; Tobacco Products; Tobacco Use
PubMed: 35272928
DOI: 10.1016/j.jadohealth.2022.01.129