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

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Menthol is one of the most important flavorings additives besides vanilla and citrus ( Kamatou et al., 2013) and is used as a cooling and/or flavors enhancing ingredient in medicines, cosmetics and insecticides, confectionery, chewing gum, liqueurs, toothpaste, shampoos, and soaps ( Patel et al., 2007; Kolassa, 2013). Menthol exhibits unique, multiple, and paradoxical sensory effects when applied externally to the skin or mucous membranes. menthol application at low doses produces a cooling sensation, whereas at higher doses, it evokes burning, irritation, and pain ( Wei and Seid, 1983; Wasner et al., 2004; Namer et al., 2005; Proudfoot et al., 2006). In practice, various topical over-the-counter products containing menthol for pain relief have concentrations ranging 5−16% (320−1024 mM) ( Oz et al., 2017). Filippov I. B., Vladymyrova I. A., Kuliieva Ie M., Skryma R., Prevarskaia N., Shuba, et al. (2009). [Modulation of the smooth muscle contractions of the rat vas deferens by TRPM8 channel agonist menthol]. Fiziol Zh (1994) 55

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). The last stage of wound repair is the extracellular matrix remodeling, in which the apoptosis of macrophages and myofibroblasts occur, ending the formation of the granulation tissue. The type III collagen is replaced with type I collagen in a process that can last for months [ 6]. In conclusion, it is seemingly that menthol administration in a great variety of experimental models and settings is associated with anti-inflammatory activity. This activity is characterized by a decrease in pro-inflammatory cytokines and related inflammatory markers, including those potentially linked to chronic inflammation, as well as pathway activation that is linked to the regulation of inflammatory enzymes and proteins. Furthermore, menthol administration in pathological inflammatory contexts appears to have favorable outcomes on histopathological characteristics of lesions and wider biological effects. As menthol is considered a safe agent for humans, given the widespread use and medical indications for menthol-containing products at present, the therapeutic potential of menthol as an anti-inflammatory can justifiably be considered on the basis of this review.Activation of TRPM8 by menthol analog icilin is reported to produce analgesia by activating central inhibitory pathways ( Chung and Caterina, 2007; Dhaka et al., 2007), which make use of inhibitory group II/III metabotropic glutamate receptors in the spinal cord (mGluRs). Numerous studies revealed that the mGluRs play a major role in modulatory central nervous system pathways and have been suggested to have pharmacological antinociceptive implications in inflammatory, neuropathic, and acute pain ( Fisher et al., 2002; Simmons et al., 2002; Chen and Pan, 2005). Chen S. R., Pan H. L. (2006). Loss of TRPV1-expressing sensory neurons reduces spinal mu opioid receptors but paradoxically potentiates opioid analgesia. J. Neurophysiol. 95 Arendt-Nielsen L., Yarnitsky D. (2009). Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. J. Pain 10 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

Menthol has demonstrated anti-inflammatory effects within the gastric mucosa in an experimental model of ethanol-induced gastric ulcers ( 37). Ethanol-induced gastric ulcers are characterized by marked inflammatory responses following the generation of reactive oxygen species and a vigorous immune reaction ( 48). The study found that menthol administration led to an increase in anti-inflammatory interleukin (IL)-10 expression, while there was a reduction in pro-inflammatory markers, including IL-6 and tumor necrosis factor-α (TNF-α). The changes in these inflammatory markers were all statistically significant compared with baseline levels (P<0.001). This study investigated the antioxidant, anti-apoptotic, and anti-inflammatory effects of menthol, providing the potential to differentiate these effects within a model whereby all three factors contribute to ulceration and associated symptoms ( 37). Importantly, menthol administration led to a reduction in markers of antioxidant activity and a reduction in the neutrophilic immune response in the gastric mucosa, which collectively suggests a gastroprotective effect. Higashi Y., Kiuchi T., Furuta K. (2010). Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: A randomized, double-blind, parallel-group, placebo-controlled, multicenter study. Clin. Ther. 32 TRP channels were first identified in a mutant breed of the fruit fly Drosophila, known as “transient receptor potential” in 1969 ( 78). From the control of cell motility and phagocytosis to the generation and release of inflammatory mediators, TRP channel-mediated effects on immune cells are undoubtedly numerous. Menthol has the potential to become a novel treatment for inflammatory illnesses due to the wide functional significance of TRP channels in inflammation and immunity ( 79). This section provides information on the role of TRP channels associated with menthol, such as TRPM8, in inflammatory diseases. TRPM8 (Transient receptor potential cation channel subfamily melastatin member 8)Hatem S., Attal N., Willer J. C., Bouhassira D. (2006). Psychophysical study of the effects of topical application of menthol in healthy volunteers. Pain 122

Fernandes E. S., Fernandes M. A., Keeble J. E. (2012). The functions of TRPA1 and TRPV1: Moving away from sensory nerves. Br. J. Pharmacol. 166 Bandell M., Story G. M., Hwang S. W., Viswanath V., Eid S. R., Petrus M. J., et al. (2004). Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41 Harrison J. L., Davis K. D. (1999). Cold-evoked pain varies with skin type and cooling rate: A psychophysical study in humans. Pain 83 Cliff M. A., Green B. G. (1994). Sensory irritation and coolness produced by menthol: Evidence for selective desensitization of irritation. Physiol. Behav. 56Decreased perceived discomfort to a greater extent and permitted greater tetanic forces to be produced. Basso L., Aboushousha R., Fan C. Y., Iftinca M., Melo H., Flynn R., et al. (2019). TRPV1 promotes opioid analgesia during inflammation. Sci. Signal. 12:eaav0711. 10.1126/scisignal.aav0711 Flühr K., Neddermeyer T. J., Lötsch J. (2009). Capsaicin or menthol sensitization induces quantitative but no qualitative changes to thermal and mechanical pain thresholds. Clin. J. Pain 25 Modaressi et al. [ 39] showed that the topical application of Mentha piperita ointment at 4% and 8% accelerated the healing of infected skin wounds in mice after 4, 8, 12, and 16 days of treatment. The authors attributed the effect mainly to the modulation of the mRNA expression of the inflammation-related genes by menthol. Babamohamadi et al. [ 40] evidenced that a Mentha piperita gel (applied three times a day up to 14 days) prevented the development of pressure ulcers in hospitalized patients. In this study, we intended to prospect the effect of menthol in skin wound healing. Skin wounds were developed in rats and treated with menthol-based creams for 3, 7, or 14 days, according to previously described stages of wound healing: inflammatory, proliferative, and tissue remodeling phase [ 9]. This is the first study evaluating the in vivo wound healing potential of menthol, and we have demonstrated that, topically applied, menthol at the concentration of 0.5% accelerated the wound closure in 3, 7, and 14 days of treatment. The mechanisms potentially involved in the effect are discussed as follows.

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