Renova Menthol Sensitive Tissues Handkerchiefs (6 Packs of 9) - Extra Soft

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Sundar et al. ( 69) and Kaur et al. ( 70) have noted that tobacco flavoring can influence the inflammatory response of cigarette smoke inhalation in the lungs. A variety of flavors added to tobacco have been associated with decreased viability of cells, decreased cell numbers in cultures, and increased levels of inflammation after exposure compared with unflavored tobacco, including when flavored with menthol ( 69). It is proposed that menthol acts on the TRPA1 receptor to activate an inflammatory response in lung parenchyma based on cell experiments and animal models of cigarette smoke inhalation ( 30, 71). Markers of inflammation elevated with menthol flavored smoke inhalation included cyclo-oxygenase-2 (COX-2) and prostaglandin levels, which are recognized as drivers of an acute local inflammatory reaction in various tissue types ( 30).

Boyd A., Bleakley C., Hurley D. A., Gill C., Hannon-Fletcher M., Bell P., et al. (2019). Herbal medicinal products or preparations for neuropathic pain. Cochrane Database Syst. Rev. 4:Cd010528. 10.1002/14651858.CD010528.pub4 Bautista D. M., Jordt S. E., Nikai T., Tsuruda P. R., Read A. J., Poblete J., et al. (2006). TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124

In addition, menthol activates TRPV3, which specifically expressed in keratinocytes (skin cells) to produce a “warm” sensation at innocuous temperatures (activation temperature is about 34−38°C) ( Peier et al., 2002; Xu et al., 2002; Macpherson et al., 2006), which would seem to explain one of the curious effects of menthol administration is that it can make human subjects report spontaneous sensations of warmth ( Green, 1985; Hatem et al., 2006). In vitro heterologous TRPV3 expressing CHO cells, 0.5−2 mM menthol induced TRPV3 currents in a concentration dependent manner, while TRPA1 and TRPV1 currents were inhibited. Also, the sensitization to TRPV3 currents was observed with repeated application of 0.5 mM menthol ( Macpherson et al., 2006). Although TRPV3 and TRPV1 share over 40% identity ( Peier et al., 2002; Smith et al., 2002; Xu et al., 2002), little research has been done on the structural features that make them functionally so different. Similar to chronic inflammation seen in other tissues, neuroinflammatory responses are linked to a range of disease states, including dementia ( 65). The protective effects of menthol administration have also been observed in the context of Parkinson’s disease models ( 44). Specifically, menthol administration has been shown to be protective against lipopolysaccharide-induced inflammatory damage to dopaminergic neurons, which are characteristically affected by Parkinson’s disease pathology ( 44). Menthol demonstrated an anti-inflammatory effect, with inhibition of pro-inflammatory enzymes and cytokines via activation of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways. During the neuroinflammatory process, Du et al. ( 44) found that menthol inhibited the increase in phosphorylation levels of p65, ERK1/2, JNK1/2, and AKT in an in vitro experiment. Menthol has been shown to increase the activation of dopaminergic neurons, but also decrease neuronal firing in cellular studies, suggesting that additional effects on the stimulation of dopaminergic neurons may also be relevant in Parkinson’s disease ( 66, 67). In terms of Alzheimer’s disease, research indicates that menthol therapy that pharmacologically raises body temperature also results in a reduction in tau phosphorylation in the brain, but not in conjunction with an inflammatory response ( 68). However, this is an area that requires further exploration, given the relative paucity of literature on menthol’s effects on neuroinflammatory pathways. Lung inflammation Bleakley C., McDonough S., MacAuley D. (2004). The use of ice in the treatment of acute soft-tissue injury: A systematic review of randomized controlled trials. Am. J. Sports Med. 32 Cohen S. P., Vase L., Hooten W. M. (2021). Chronic pain: An update on burden, best practices, and new advances. Lancet 397 Hans M., Wilhelm M., Swandulla D. (2012). Menthol suppresses nicotinic acetylcholine receptor functioning in sensory neurons via allosteric modulation. Chem. Senses 37

As 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 pathwaysDani J. A., Bertrand D. (2007). Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu. Rev. Pharmacol. Toxicol. 47 Neuropathy is one of the most common long-term complications of diabetes, characterized by altered thermal, mechanical, and chemical sensation. Of three large, clinic-based studies from Europe, the prevalence of diabetic neuropathy varied from 23–29% ( Young et al., 1993; Tesfaye et al., 1996; Cabezas-Cerrato, 1998). Preclinical studies have shown that there was an increase in TRPV1-mediated currents but a decrease in TRPM8-mediated currents in DRG isolated from diabetic hyperalgesia mice. Therefore, menthol, which has the effect of targeting TRPV1 or TRPM8, may be a useful approach to treat pain associated with diabetic neuropathy ( Pabbidi and Premkumar, 2017). There has been a randomized, double-blind, placebo-controlled crossover trial of the efficacy and safety of menthol topically alone or in combination with mannitol in the relief of diabetic neuropathy ( {"type":"clinical-trial","attrs":{"text":"NCT02728687","term_id":"NCT02728687"}}NCT02728687), with no results have been reported.