The author would like to thank the support of National University Student Innovation Program of China from Chengdu University of Traditional Chinese Medicine (No. 202110633026). Conflict of interest Tsoupras A, Lordan R, Zabetakis I. Inflammation, not cholesterol, is a cause of chronic disease. Nutrients (2018) 10(5):604. doi: 10.3390/nu10050604 Balsam tissues in regular are my favourites, as they are strong and the box is not too big, so I can put it nearly anywhere in the house.

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Norões MM, Santos LG, Gavioli EC, de Paula Soares Rachetti V, Otuki MF, de Almeida Cabrini D, et al. Role of TRPA1 receptors in skin inflammation induced by volatile chemical irritants in mice. Eur J Pharmacol (2019) 858:172460. doi: 10.1016/j.ejphar.2019.172460Lange BM. Biosynthesis and biotechnology of high-value p-menthane monoterpenes, including menthol, carvone, and limonene. Biotechnol Isoprenoids (2015) 22:319–53. doi: 10.1007/10_2014_289 Taken together, studies exploring the protective effects of menthol against inflammatory damage, or association with protection against chronic inflammation, are indicative of potential therapeutic applications of the compound. However, it is vital to note the limitations of the studies completed to date. One main limitation is that most of the studies are either in vitro or based on animal models of human disease, which may limit our direct application to human pathology. While menthol has been extensively used therapeutically in humans, demonstration of a clear anti-inflammatory effect should be sought and evaluated using biochemical markers or inflammation in a pathological context. Furthermore, while the evidence for the anti-inflammatory effects of menthol is compelling, additional insights may be needed to clarify the mechanisms of action and the clinical relevance of any anti-inflammatory effects. This is especially noteworthy considering the evidence for the pro-inflammatory impact of inhaled menthol when combined with cigarette smoking ( 42). Inflammatory cascades are complex and closely related to immunological function and antioxidant activity in multiple tissues; further delineation of these mechanisms and pathways is needed to truly appreciate the potential for menthol, which appears to be a molecule with multiple cellular targets, as a therapeutic anti-inflammatory compound. Author contributions Eccles, R. (1994). "Menthol and Related Cooling Compounds". J. Pharm. Pharmacol. 46 (8): 618–630. doi: 10.1111/j.2042-7158.1994.tb03871.x. PMID 7529306. S2CID 20568911. Liu B, Fan L, Balakrishna S, Sui A, Morris JB, Jordt SE. TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. Pain® (2013) 154(10):2169–77. doi: 10.1016/j.pain.2013.06.043

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Andersen HH, Melholt C, Hilborg SD, Jerwiarz A, Randers A, Simoni A, et al. Antipruritic effect of cold-induced and transient receptor potential-agonist-induced counter-irritation on histaminergic itch in humans. Acta Dermato-venereol (2017) 97(1):63–7. doi: 10.2340/00015555-2447 Cosens DJ, Manning A. Abnormal electroretinogram from a drosophila mutant. Nature (1969) 224(5216):285–7. doi: 10.1038/224285a0 Chen H, Li M. Role of mammalian target of rapamycin activation in menthol-induced expressions of airway inflammation-related factors in human bronchial epithelial cells in vitro. Nan fang Yi Ke Da Xue Xue Bao (2019) 39(11):1344–9. doi:10.12122/j.issn.1673-4254.2019.11.12 Rozza AL, Beserra FP, Vieira AJ, Oliveira de Souza E, Hussni CA, Martinez ERM, et al. The use of menthol in skin wound healing–Anti-Inflammatory potential, antioxidant defense system stimulation and increased epithelialization. Pharmaceutics (2021) 13(11):1902. doi: 10.3390/pharmaceutics13111902As a naturally occurring cyclic monoterpene, menthol may utilize its chemical structure (e.g., hydroxyl groups) for its potent antioxidant effects. Several previous studies have concluded that the major monoterpenoids, particularly menthol, are responsible for the majority of the mint’s antioxidant activity ( 11, 12). In general, phytochemicals exert their antioxidant effects by scavenging free radicals, chelating divalent metals, donating hydrogen or electrons, and facilitating the decomposition of peroxyl radicals. As a result, phytochemicals can inhibit the formation of free radicals, slow or inhibit the autoxidation process (chain-breaking antioxidant), or accelerate the termination of autoxidation. Wu et al. ( 12) use in vitro chemical- and cell-based assays and in vivo tests with C. elegans model to prove that the major monoterpenoids of mint essential oil, particularly menthol, have potent antioxidant effects. Biological activity of menthol: receptor activity and signaling pathways The findings of Lin et al. ( 32) contrast with those observed by Liu et al. ( 42), who investigated the effects of menthol (L-menthol) on cigarette smoke extract (CSE) induced lung injury in rats. The study found that following CSE injury, which is characterized by acute oxidative and inflammatory damage to the lung tissue, administration of menthol led to a marked reduction in the inflammatory response. Specifically, IL-1β, IL-6, and TNF-α were downregulated following the activation of the NF-кB and MAPK pathways ( 42). Liu et al. ( 72) had previously observed that menthol administration suppressed hypersensitivity to cigarette smoke in the context of a chronic inflammatory state, validating these observations. TRPM8, also known as the cold and menthol receptor 1 (CMR1), is a protein encoded by the TRPM8 gene in humans. It is generally known that menthol is the agonist of TRPM8. The well-known chilling feeling that menthol causes when breathed, consumed, or applied to the skin is brought about by its capacity to chemically activate the cold-sensitive TRPM8 receptors in the skin. However, TRPM8 appears to perform far more functions than simply bringing coldness ( 6, 55, 79). As mentioned above, menthol-induced TRPM8 also plays an important physiological role in inflammation. Atkinson, R. W.; Yoshida, H. (1882). "On peppermint camphor (menthol) and some of its derivatives". J. Chem. Soc., Trans. 41: 49. doi: 10.1039/CT8824100049.

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Du J, Liu D, Zhang X, Zhou A, Su Y, He D, et al. Menthol protects dopaminergic neurons against inflammation-mediated damage in lipopolysaccharide (LPS)-evoked model of parkinson’s disease. Int Immunopharmacol (2020) 85:106679. doi: 10.1016/j.intimp.2020.106679 Results: The decrease in pro-inflammatory cytokines and related inflammatory markers, as well as associated pathway activation, was found to play the greatest role in the protective effects of menthol against inflammatory damage or association with protection against chronic inflammation. I'm loving the balm tissues - am in Finland right now, and have a streaming cold which is not pretty in walking to the office in -9c. The olbas oil tissues which I found in my handbag first gave me an unattractive aura and made my face sting, but the balm tissues don't make me smell with one up my sleeve and I'm not bright red of nose. The tin of balm is not going well as I can't hold it with my disabled hand, and you can't open it one handed. In perfumery, menthol is used to prepare menthyl esters to emphasize floral notes (especially rose). Despite the uncertainty over the value of topical menthol in reducing inflammation that is established in the skin, the anti-inflammatory effects of menthol have been proposed to influence wound healing, as investigated by Rozza et al. ( 61). Skin wound healing is a complex process that includes an inflammatory phase, whereby reductions in inflammatory markers, including IL-6, have been linked to accelerated skin wound healing ( 61). In this study, the authors evaluated the effects of different periods of time of treatment with menthol (3, 7, or 14 days) in rats with skin wounds, comparing collagenase-based and menthol-based creams. The menthol-based cream led to accelerated healing within the first three days of treatment, which is consistent with a reduction in the initial inflammatory phase of wound healing when compared with collagenase-based creams. Furthermore, this healing was linked to a reduction in pro-inflammatory cytokines TNF-α and IL-6 (reduced expression of mRNA). Over time, menthol-based treatment was found to not only decrease pro-inflammatory cytokine levels through the inflammatory, proliferative, and remodeling phases of wound healing.

Natural menthol is obtained by freezing peppermint oil. The resultant crystals of menthol are then separated by filtration. Helyes Z, Sándor K, Borbély E, Tékus V, Pintér E, Elekes K, et al. Involvement of transient receptor potential vanilloid 1 receptors in protease-activated receptor-2-induced joint inflammation and nociception. Eur J Pain (London England) (2010) 14(4):351–8. doi: 10.1016/j.ejpain.2009.07.005 Kanezaki M, Ebihara S, Gui P, Ebihara T, Kohzuki M. Effect of cigarette smoking on cough reflex induced by TRPV1 and TRPA1 stimulations. Respir Med (2012) 106(3):406–12. doi: 10.1016/j.rmed.2011.12.007 Shahid M, Lee MY, Yeon A, Cho E, Sairam V, Valdiviez L, et al. Menthol, a unique urinary volatile compound, is associated with chronic inflammation in interstitial cystitis. Sci Rep (2018) 8(1):1–12. doi: 10.1038/s41598-018-29085-3 Umezu T. Identification of novel target molecules of l-menthol. Heliyon (2021) 7(6):e07329. doi: 10.1016/j.heliyon.2021.e07329