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Biomedicine & Pharmacotherapy =... Oct 2022Mentha (also known as peppermint), a genus of plants in the taxonomic family Lamiaceae (mint family), is widely distributed throughout temperate regions of the world.... (Review)
Review
Mentha (also known as peppermint), a genus of plants in the taxonomic family Lamiaceae (mint family), is widely distributed throughout temperate regions of the world. Mentha contains various constituents that are classified as peppermint essential oil (PEO) and non-essential components. PEO, consisting mainly of menthol, menthone, neomenthol and iso-menthone, is a mixture of volatile metabolites with anti-inflammatory, antibacterial, antiviral, scolicidal, immunomodulatory, antitumor, neuroprotective, antifatigue and antioxidant activities. Mounting evidence indicates that PEO may pharmacologically protect gastrointestinal, liver, kidney, skin, respiratory, brain and nervous systems, and exert hypoglycemic and hypolipidemic effects. Clinically, PEO is used for gastrointestinal and dermatological diseases, postoperative adjuvant therapy and other fields. This review aims to address the advances in the extraction and isolation of PEO, its biological activities, pharmacological effects, toxicity and applications, with an emphasis on the efficacy of PEO on burn wounds and psoriasis, providing a comprehensive foundation for research, development and application of PEO in future.
Topics: Lamiaceae; Mentha piperita; Menthol; Oils, Volatile
PubMed: 35994817
DOI: 10.1016/j.biopha.2022.113559 -
Science (New York, N.Y.) Oct 2022The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in...
The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in mammals. TRPM8 activation is controlled by cooling compounds together with the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP). Our knowledge of cold sensation and the therapeutic potential of TRPM8 for neuroinflammatory diseases and pain will be enhanced by understanding the structural basis of cooling agonist- and PIP-dependent TRPM8 activation. We present cryo-electron microscopy structures of mouse TRPM8 in closed, intermediate, and open states along the ligand- and PIP-dependent gating pathway. Our results uncover two discrete agonist sites, state-dependent rearrangements in the gate positions, and a disordered-to-ordered transition of the gate-forming S6-elucidating the molecular basis of chemically induced cool sensation in mammals.
Topics: Animals; Mice; Cold Temperature; Cryoelectron Microscopy; Ligands; Menthol; TRPM Cation Channels; Phosphatidylinositol 4,5-Diphosphate; Thermosensing; Ion Channel Gating; Protein Conformation; Pyrimidinones
PubMed: 36227998
DOI: 10.1126/science.add1268 -
Nature Communications Dec 2022Protein Phosphatase 6 down-regulation in keratinocytes is a pivotal event that amplifies the inflammatory circuits in psoriasis, indicating that restoration of protein...
Protein Phosphatase 6 down-regulation in keratinocytes is a pivotal event that amplifies the inflammatory circuits in psoriasis, indicating that restoration of protein phosphatase 6 can be a rational strategy for psoriasis treatment. Through the phenotypic screen, we here identify L-menthol that ameliorates psoriasis-like skin inflammation by increasing protein phosphatase 6 in keratinocytes. Target identification approaches reveal an indispensable role for the transcription factor hairy and enhancer of split 1 in governing the protein phosphatase 6-upregulating function of L-menthol in keratinocytes. The transcription factor hairy and enhancer of split 1 is diminished in the epidermis of psoriasis patients and imiquimod-induced mouse model, while L-menthol upregulates the transcription factor hairy and enhancer of split 1 by preventing its proteasomal degradation. Mechanistically, the transcription factor hairy and enhancer of split 1 transcriptionally activates the expression of immunoglobulin-binding protein 1 which promotes protein phosphatase 6 expression and inhibits its ubiquitination. Collectively, we discover a therapeutic compound, L-menthol, for psoriasis, and uncover the dysfunctional the transcription factor hairy and enhancer of split 1- immunoglobulin-binding protein 1- protein phosphatase 6 axis that contributes to psoriasis pathology by using L-menthol as a probe.
Topics: Animals; Mice; Menthol; Psoriasis; Keratinocytes; Transcription Factors; Immunoglobulins; Disease Models, Animal; Transcription Factor HES-1
PubMed: 36535970
DOI: 10.1038/s41467-022-35565-y -
Frontiers in Pharmacology 2023Menthol, a widely used natural, active compound, has recently been shown to have anticancer activity. Moreover, it has been found to have a promising future in the... (Review)
Review
Menthol, a widely used natural, active compound, has recently been shown to have anticancer activity. Moreover, it has been found to have a promising future in the treatment of various solid tumors. Therefore, using literature from PubMed, EMBASE, Web of Science, Ovid, ScienceDirect, and China National Knowledge Infrastructure databases, the present study reviewed the anticancer activity of menthol and the underlying mechanism. Menthol has a good safety profile and exerts its anticancer activity multiple pathways and targets. As a result, it has gained popularity for significantly inhibiting different types of cancer cells by various mechanisms such as induction of apoptosis, cell cycle arrest, disruption of tubulin polymerization, and inhibition of tumor angiogenesis. Owing to the excellent anticancer activity menthol has demonstrated, further research is warranted for developing it as a novel anticancer agent. However, there are limitations and gaps in the current research on menthol, and its antitumor mechanism has not been completely elucidated. It is expected that more basic experimental and clinical studies focusing on menthol and its derivatives will eventually help in its clinical application as a novel anticancer agent.
PubMed: 37007039
DOI: 10.3389/fphar.2023.1148790 -
Frontiers in Pharmacology 2021Menthol, the main monoterpene found in L. () is known to modulate nociceptive threshold and is present in different curative preparations that reduce sensory...
Menthol, the main monoterpene found in L. () is known to modulate nociceptive threshold and is present in different curative preparations that reduce sensory hypersensitivities in pain conditions. While for pulegone, a menthol-like monoterpene, only a limited number of studies focus on its putative analgesic effects, pulegone is the most abundant monoterpene present in (L.) Savi (), a plant of the Lamiaceae family used in traditional medicine to alleviate rheumatic disorders, which counts amongst chronic inflammatory diseases. Here, we analyzed the monoterpenes composition of and . We then compared the putative anti-hyperalgesic effects of the main monoterpenes found, menthol and pulegone, in acute inflammatory pain conditions. and extracts were obtained through pressurized liquid extraction and analyzed by gas chromatography-mass spectrometry. The anti-inflammatory activity of menthol or pulegone was evaluated by measuring the secretion of the tumour necrosis factor alpha (TNF α) from LPS-stimulated THP-1 cells. The anti-hyperalgesic effects of menthol and pulegone were tested on a rat inflammatory pain model. Pulegone and menthol are the most abundant monoterpene found in (49.41%) and (42.85%) extracts, respectively. , both pulegone and menthol act as strong anti-inflammatory molecules, with EC50 values of 1.2 ± 0.2 and 1.5 ± 0.1 mM, respectively, and exert cytotoxicity with EC50 values of 6.6 ± 0.3 and 3.5 ± 0.2 mM, respectively. , 100 mg/kg pulegone exerts a transient anti-hyperalgesic effect on both mechanical (pulegone: 274.25 ± 68.89 g, = 8; vehicle: 160.88 ± 35.17 g, = 8, < 0.0001), thermal heat (pulegone: 4.09 ± 0.62 s, = 8; vehicle: 2.25 ± 0.34 s, = 8, < 0.0001), and cold (pulegone: 2.25 ± 1.28 score, = 8; vehicle: 4.75 ± 1.04 score, = 8, = 0.0003). In a similar way, 100 mg/kg menthol exerts a transient anti-hyperalgesic effect on both mechanical (mechanical: menthol: 281.63 ± 45.52 g, = 8; vehicle: 166.25 ± 35.4 g, = 8, < 0.0001) and thermal heat (menthol: 3.65 ± 0.88 s, = 8; vehicle: 2.19 ± 0.26 s, = 8, <0.0001). Here, we show that both pulegone and menthol are anti-inflammatory and anti-hyperalgesic monoterpenes. These results might open the path towards new compound mixes to alleviate the pain sensation.
PubMed: 34916937
DOI: 10.3389/fphar.2021.753873 -
International Journal of Environmental... Mar 2023Oral Nicotine Pouches (ONPs) are the new form of nicotine pouches that have become a type of emerging smokeless tobacco product sold by various tobacco companies. These... (Review)
Review
INTRODUCTION
Oral Nicotine Pouches (ONPs) are the new form of nicotine pouches that have become a type of emerging smokeless tobacco product sold by various tobacco companies. These smokeless tobacco products are marketed for usage all over as snus containing tobacco-derived nicotine (natural) or as tobacco-free nicotine (synthetic) as substitutes for other tobacco products. Based on perception and socio-behavioral aspects, ONPs have become popular tobacco products among adolescents/young adults, and over 50% of young adult users of ONP use flavored ONPs, such as menthol/mint, tobacco, dessert/candy, and fruity, which are the most popular flavors. Various new ONP flavors are currently popular locally as well as in the online market. Tobacco, menthol, and fruit-flavored ONPs could motivate cigarette smokers to change to ONPs.
METHODS
We expanded our knowledge on natural/synthetic ONP flavor wheels to available data on ONPs, describing, in detail, their flavors and brands (US and Europe) in both natural and synthetic ONP categories. We classified over 152 snus and 228 synthetic ONPs into the following flavor categories: "Tobacco", "Menthol/Mint", "Fruity", "Candy/Deserts", "Drink", "Aroma", "Spices", and "Mixed Flavors".
RESULTS
Based on total numbers, we found the most popular ONP flavors, sold as tobacco and menthol, to be among natural ONPs; among synthetic ONPs, fruity and menthol are the most prominent flavors, with varying concentrations of nicotine and other flavoring chemicals, including coolant WS-23. We also showed possible molecular targets and toxicities, due to exposure to ONPs, activating several signaling cascades such as AKT and NF-kappaB, which might possibly lead to apoptosis and epithelial mesenchymal transition (EMT).
CONCLUSIONS
Considering the marketing of ONP products with various flavor profiles and with most of these products containing tobacco/menthol/fruit flavor, it is likely to have regulation and a marketing disclaimer on some of these products. Further, it would be logical to determine how the market reacts in terms of compliance and non-compliance with flavor restrictions by the regulatory agencies.
Topics: Young Adult; Adolescent; Humans; Nicotine; Menthol; Flavoring Agents; Electronic Nicotine Delivery Systems; Tobacco Products; Vaping; Perception
PubMed: 36901533
DOI: 10.3390/ijerph20054526 -
Preventive Medicine Reports Dec 2021This study examines patterns of use for menthol/non-menthol cigarettes and Electronic Nicotine Delivery Systems (ENDS) from 2013 to 2019 among U.S. adults. We calculated...
This study examines patterns of use for menthol/non-menthol cigarettes and Electronic Nicotine Delivery Systems (ENDS) from 2013 to 2019 among U.S. adults. We calculated the weighted population prevalence of current exclusive and dual use for each product (i.e., menthol/non-menthol cigarettes and ENDS) stratified by age, sex, race/ethnicity, household income, and education in all surveys using data from three nationally representative surveys: the Population Assessment of Tobacco and Health (PATH) Study Waves 1-4 (W1-W4), 2013-2018; the National Health Interview Survey (NHIS) 2015; and the Tobacco Use Supplement to the Current Population Survey (TUS-CPS) 2014-2015 (T1) and 2018-2019 (T2). Exclusive non-menthol cigarette use (PATH: 9.0%W1, 9.4%W4; NHIS: 8.7%; TUS-CPS: 8.1%T1, 6.9%T2) and dual non-menthol cigarette/ENDS use (PATH: 2.4%W1, 1.5%W4; NHIS: 1.5%; TUS-CPS: 1.1%T1, 0.6%T2) were the most common single and dual tobacco use patterns, respectively, across all surveys. Both exclusive menthol cigarette use (3.9%T1-3.3%T2) and non-menthol cigarette use (8.1%T1-6.9%T2) declined in TUS-CPS from 2014/5-2018/9. Dual menthol cigarette/ENDS use also declined (PATH: 1.5%W1-1.1%W4; TUS-CPS: 0.5%T1-0.3%T2), as did dual non-menthol cigarette/ENDS use (PATH: 2.4%W1-1.5%W4; TUS-CPS 1.1%T1-0.6%T2). Across surveys, exclusive menthol cigarette use and dual menthol cigarette/ENDS use were more common among individuals aged 25-34 years old; non-Hispanic Blacks (NHBs); and low-income earners. Single and dual use patterns of menthol/non-menthol cigarettes and ENDS have declined over time. Nevertheless, certain vulnerable population groups, including NHBs and low-income earners, disproportionately use exclusive menthol cigarettes and dual menthol cigarette/ENDS, making menthol bans a potential policy target for reducing tobacco-related health disparities.
PubMed: 34976632
DOI: 10.1016/j.pmedr.2021.101566 -
Journal of Addictive Diseases 2022Menthol cigarette use among women who smoke cigarettes during pregnancy is high, but little is known about the factors that contribute to preference for menthol...
BACKGROUND
Menthol cigarette use among women who smoke cigarettes during pregnancy is high, but little is known about the factors that contribute to preference for menthol cigarette use during pregnancy.
OBJECTIVE
This study investigated preferences, perceptions, and intentions to use menthol vs. non-menthol cigarettes in a sample of pregnant women.
METHODS
Pregnant women ( = 124, = 26.2 years, 50% minorities) completed a study investigating the impact of maternal smoking on biobehavioral markers of fetal risk. During the third trimester, participants self-reported preferences (liking, attractiveness, smoothness, interest), perceptions of harm (general, pregnancy-specific), and intentions to use menthol and non-menthol cigarettes. We examined differences in responses based on whether participants endorsed (1) cigarette use during pregnancy (yes/no) and (2) lifetime cigarette use (yes/no).
RESULTS
Sixty-two participants endorsed cigarette smoking during pregnancy (85.5% smoked menthol cigarettes), and 94 participants reported lifetime use. Overall, menthol cigarettes were perceived as more likeable and smoother vs. non-menthol (s < .001) - even among participants who never smoked cigarettes (s < .05). All participants rated both menthol and non-menthol cigarette use as harmful. Compared to participants who did not smoke during pregnancy, participants who smoked during pregnancy rated menthol cigarettes as less harmful for pregnant women ( = .001), while there were no differences between groups in harm perceptions toward non-menthol cigarettes.
CONCLUSIONS
Menthol may increase cigarettes appeal for pregnant women. Implications for regulation of menthol cigarettes are discussed. Future studies may investigate the role of sensory perception, marketing, and health education in influencing these factors.
Topics: Adult; Cigarette Smoking; Female; Humans; Intention; Male; Menthol; Pregnancy; Pregnant Women; Tobacco Products
PubMed: 34751106
DOI: 10.1080/10550887.2021.1981123 -
Nicotine & Tobacco Research : Official... Jan 2021To study the association between health care utilization and menthol cigarette use and whether the association differed between African American (AA) and non-AA smokers.
INTRODUCTION
To study the association between health care utilization and menthol cigarette use and whether the association differed between African American (AA) and non-AA smokers.
METHODS
We analyzed the three most recent 2005, 2010, and 2015 National Health Interview Survey Cancer Control Supplements. After incorporating propensity score weights adjusting for observed differences between menthol and non-menthol users, we estimated Zero-Inflated Poisson models on hospital nights, emergency department visits, doctor visits, and home visits as a function of menthol use status and other covariates separately for current cigarette smokers and recent quitters (former smokers quitting cigarette smoking ≤ 4 years).
RESULTS
Although current menthol smokers smoked fewer cigarettes per day than current non-menthol smokers, they did not differ from current non-menthol smokers in health care utilization. Among recent quitters, those who used to smoke menthol cigarettes had higher odds of having hospital nights than those who used to smoke non-menthol cigarettes. However, we did not find any significant association between menthol use and other health care utilization-emergency department visits, doctor visits, and home visits-among recent quitters. Moreover, compared with non-AA recent quitters, AA recent quitters had higher odds of having home visits, but fewer home visits, if they used to smoke menthol cigarettes.
CONCLUSION
Menthol use was associated with greater hospitalization among recent quitters, and the association between home visits and menthol use differed between AA and non-AA recent quitters.
IMPLICATIONS
This is the first study that used econometric models to study the association between health care utilization and menthol cigarette use and examine whether the association differed between AA and non-AA smokers. Our study found health care utilization did not differ by menthol use status for current smokers, although current menthol smokers smoked fewer cigarettes per day than current non-menthol smokers. However, we found menthol use was associated with higher odds of having hospital nights for recent quitters. We also found AA recent quitters had a different association between home visits and menthol use compared with non-AA recent quitters.
Topics: Adolescent; Adult; Black or African American; Aged; Cigarette Smoking; Cross-Sectional Studies; Female; Health Expenditures; Humans; Male; Menthol; Middle Aged; Non-Smokers; Patient Acceptance of Health Care; Smokers; United States; White People; Young Adult
PubMed: 32623471
DOI: 10.1093/ntr/ntaa122 -
Pain Feb 2021
Topics: Ankyrins; Humans; Menthol; Neurogenic Inflammation; Nociception; Pain; Receptors, Nerve Growth Factor
PubMed: 32826762
DOI: 10.1097/j.pain.0000000000002044