Guaifenesin 100mg/5ml / Levomenthol 1.1mg/5ml oral solution 5ml sachets

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 via 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.

Abstract licence: CC BY

OBJECTIVES: To assess the quality of evidence on the effectiveness of local US laws restricting the sale of flavored tobacco products. METHODS: We conducted a systematic search and qualitative scoping review of English-language papers published through May 2020 that evaluated flavored tobacco sales policies implemented by US jurisdictions during 2010-2019. We constructed a conceptual model for flavored and menthol tobacco sales restriction outcomes, assigned GRADE quality of evidence ratings to policy outcomes evaluated through the included studies, and summarized factors that might explain weak or inconsistent findings. RESULTS: We found moderate to high quality of evidence associating policy implementation with reduced availability, marketing, and sales of policy-restricted products, and decreased youth and adult tobacco use of these products; however, policy exclusions and exemptions, implementation challenges, tobacco industry actions (e.g., marketing of concept-named flavored products; exploiting policy exemptions for certain store types), and consumer responses (e.g., cross-border or illicit purchasing) might undermine or mitigate intended policy effects. CONCLUSIONS: Flavored and menthol tobacco product sales restrictions implemented and evaluated in US jurisdictions appear to have achieved some of their intended outcomes; however, deficiencies in study designs, methods, and metrics could contribute to equivocal findings on quality of evidence associating policy implementation and outcomes. Gaps in the evidence are beginning to be filled with research using more rigorous study designs, improved measurement and analytic methods, and longer-term follow-up. IMPLICATIONS: In the absence of comprehensive federal action, US jurisdictions have the obligation to restrict flavored and menthol product sales to protect vulnerable populations from tobacco-related harms. The considerable expenditure of financial resources, political will, and time dedicated to policy adoption and implementation argue for evaluation studies designed to maximize the quality of evidence. This review offers generalizable insights into evaluation findings that can inform efforts to enhance tobacco control policy implementation and impact in the US and globally.

Abstract licence: CC BY-NC-ND

Menthol is an important flavoring additive that triggers a cooling sensation. Under physiological condition, low to moderate concentrations of menthol activate transient receptor potential cation channel subfamily M member 8 (TRPM8) in the primary nociceptors, such as dorsal root ganglion (DRG) and trigeminal ganglion, generating a cooling sensation, whereas menthol at higher concentration could induce cold allodynia, and cold hyperalgesia mediated by TRPM8 sensitization. In addition, the paradoxical irritating properties of high concentrations of menthol is associated with its activation of transient receptor potential cation channel subfamily A member 1 (TRPA1). Under pathological situation, menthol activates TRPM8 to attenuate mechanical allodynia and thermal hyperalgesia following nerve injury or chemical stimuli. Recent reports have recapitulated the requirement of central group II/III metabotropic glutamate receptors (mGluR) with endogenous κ-opioid signaling pathways for menthol analgesia. Additionally, blockage of sodium channels and calcium influx is a determinant step after menthol exposure, suggesting the possibility of menthol for pain management. In this review, we will also discuss and summarize the advances in menthol-related drugs for pathological pain treatment in clinical trials, especially in neuropathic pain, musculoskeletal pain, cancer pain and postoperative pain, with the aim to find the promising therapeutic candidates for the resolution of pain to better manage patients with pain in clinics.

Abstract licence: CC BY

Background: Rising incidence of inflammation-related diseases is an increasing concern nowadays. However, while menthol is a wildly-used and efficacious complementary medicine, its pharmacological mechanism still remains uncertain. Superimposed upon that, the aim of this review is to summarize the contemporary evidence of menthol's anti-inflammatory activity. Methods: Using the pharmacopeias and electronic databases, including Web of Science, PubMed, and CNKI, this study analyzed the relevant research articles and review articles from 2002 to 2022 and concluded those results and conjectures to finish this article. 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. Conclusion: This review mainly concludes the progress in menthol's anti-inflammatory activity. Further studies are needed to establish relationships between the mechanisms of action and to clarify the clinical relevance of any anti-inflammatory effects.

Abstract licence: CC BY

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.

Abstract licence: CC BY