Methyl salicylate 30% / Menthol 8% cream

IntroductionTopical salicylates are commonly found in over-the-counter medications and are applied for pain relief or to treat dermatologic conditions. While generally considered safe, they can cause systemic toxicity under certain conditions. We conducted a systematic review of topical salicylate toxicity. This comprehensive review of previously reported cases highlights the risks, clinical presentations, and management considerations of systemic toxicity from topical salicylates.MethodsWe present a new case of topical salicylate toxicity and conducted a comprehensive systematic literature search from 1952-2024 using PubMed, Google, and Google Scholar. Our search was supplemented by cross-referencing previous studies to identify cases and reviews of topical salicylate toxicity. We then performed a descriptive analysis of the cases, summarizing key information such as clinical presentation, blood levels, and outcomes. Findings were used to contextualize the risks and clinical manifestations of topical salicylate toxicity.ResultsA total of 44 cases of topical salicylate toxicity, including our index case, were identified and included in our analysis. Most cases involved patients > 40 years of age, but all age ranges were represented, including neonates. The most frequently reported symptoms included tachypnea (32.5%) and vomiting (25.5%). The new case was an elderly male with further altered mental status from baseline dementia and elevated anion gap.ConclusionBoth the new case and the literature review emphasize the continued potential systemic risks of topical salicylates among a broad demographic. Given the variable presentations, clinicians should maintain a high index of suspicion for salicylate toxicity in patients with unexplained altered metabolic and/or mental status. Early consideration, recognition, and intervention of topical salicylates-induced toxicity is essential for good outcomes. As many of these products are heavily advertised, patient education on the appropriate use of topical salicylates may be crucial to prevent inadvertent toxicity.

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Plantar fasciitis is the most common cause of heel pain in adults with an overall prevalence of 0.85% in the adult population of the US, affecting over 2 million adults annually. Most current treatment modalities are not supported by sufficient evidence to recommend one particular strategy over another. Topical application of analgesics for soft tissue pain is well established, however the plantar fascia presents challenges in this regard due to thick skin, fibrotic tissue, and an often thickened fat pad. Sixty-two patients with plantar fasciitis were randomized to a placebo controlled trial testing the efficacy of a topical solution of plant terpenes containing camphor, menthol, eugenol, eucalyptol, and vanillin. Skin permeation of the mixture was enhanced with 15% dimethylsulfoxide (DMSO), 1% limonene, and rosemary oil. One ml of solution was applied topically twice daily, and pain scores evaluated on Day 0, Day 1, Day 3, and Day 10. Using the validated foot function index 78.1% of patients reported an 85% or greater decrease in their total pain score by day 10 while placebo treatment was without effect (One Way ANOVA, P < 0.01). This study adapts the treatment modality of topical analgesia for soft tissue pain to a problematic area of the body and shows therapeutic promise.ClinicalTrials.gov Identifier: NCT05467631.

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IntroductionMethyl salicylate, the main compound of wintergreen oil, is widely used in topical applications. However, its vascular and thermosensory effects are not fully understood. The primary aim was to investigate the effects of topical methyl salicylate on skin temperature (Tskin), skin microcirculation (MCskin) and muscle oxygen saturation (SmO2) compared to a placebo gel. The secondary aim was to assess thermosensory responses (thermal sensation, thermal comfort) and to explore to which extent these sensations correspond to the physiological responses over time.Methods21 healthy women (22.2 ± 2.9 years) participated in this single-blind, randomized controlled trial. Custom-made natural wintergreen oil (12.9%), containing methyl salicylate (>99%) and a placebo gel, 1 g each, were applied simultaneously to two paravertebral skin areas (5 cm × 10 cm, Th4-Th7). Tskin (infrared thermal imaging), MCskin (laser speckle contrast imaging) and SmO2 (deep tissue oxygenation monitoring) and thermosensation (Likert scales) were assessed at baseline (BL) and at 5-min intervals during a 45 min post-application period (T0-T45).ResultsBoth gels caused an initial decrease in Tskin, with Tskin(min) at T5 for both methyl salicylate (BL-T5: Δ-3.36°C) and placebo (BL-T5: Δ-3.90°C), followed by a gradual increase (p skin than placebo between T5 and T40 (p skin increased, with MCskin(max) at T5 (BL-T5: Δ88.7%). For placebo, MCskin decreased (BL-T5: Δ-17.5%), with significantly lower values compared to methyl salicylate between T0 and T45 (p 2, with no significant differences between methyl salicylate and placebo (p > .05). Thermal sensation responses to topical methyl salicylate ranged from "cool" to "hot", with more intense sensations reported at T5.DiscussionThe findings indicate that topical methyl salicylate induces short-term cutaneous vasodilation, but it may not enhance skeletal muscle blood flow. This study highlights the complex sensory responses to its application, which may be based on the short-term modulation of thermosensitive transient receptor potential channels.

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Common cold viruses are leading triggers of asthma attacks, causing nearly two million hospitalizations per year and productivity losses approaching $40B. They also increase susceptibility to bacterial infections driving antibiotic use. Post-market clinical studies have questioned the efficacy of most over the counter (OTC) cough and cold ingredients against placebo in treating various symptoms. To our knowledge, only aspirin significantly improved overall illness severity compared to placebo and that was by about 25-30%. In this double-blind randomized placebo-controlled trial involving 157 participants, we sought to determine whether a throat spray containing a mucosal immune complex (MIC) (comprised of lysozyme, lactoferrin, and aloe) along with anti-inflammatory salicylates can increase the hereto reported efficacy of aspirin at reducing common cold symptoms. Previously published reports showed that the MIC can protect respiratory epithelia and lower inflammatory cytokines. Salicylates are naturally occurring plant compounds found in many common foods as well as wintergreen oil and are chemically similar precursors to aspirin (acetyl salicylate). Participants self-administered treatments (throat sprays every hour and tablets every four hours) and completed surveys at home over two days. Treatments included MIC spray mixed with 6 mg aspirin + placebo tablet (Treatment 1), MIC spray mixed with 6 mg wintergreen oil+ placebo tablet (Treatment 2), MIC spray mixed with 6mg wintergreen oil+ 325 mg aspirin tablet (Treatment 3). Participants included adult volunteers ages 21-66 (average 44), 54% female, 46% male, 46% African American, 8% Asian, 39% Caucasian, and 7% Hispanic, having common cold symptoms lasting less than two days. The main outcome measures included Sore Throat Pain Intensity (STPIS) 0-100 at 36 hours (primary endpoint) and Modified Jackson Score (MJS), a combination of eight cold symptoms (secondary endpoint). Both primary and secondary endpoints were met. Sore throat pain as measured by STPIS decreased 68-75% by 36 hours depending on treatment. Other symptoms such as nasal discharge, congestion, sneezing, cough, sore throat, and malaise as measured by MJS decreased 38-68% depending on treatment. In repeated measure within group analysis observing the same participants over multiple time points; the mean change of STPIS values and their percentage change from baseline to 36 hours were as follows: Placebo (-7.84 [95% CI -14.20 to -1.47];(-14%)), Treatment 1 (-42.41 [95% CI -48.30 to -36.52];(-75%)), Treatment 2 (-38.60 [95% CI -46.64 to -31.56];(-68%)), and Treatment 3 (-44.19 [95% CI -52.11 to -36.27];(-79%)). In repeated measure within group analysis all treatments significantly reduced cold symptom severity (MJS) from Days 1-2. Results were as follows: Treatment 1 (-2.26 [95% CI -3.04 to -1.47] (-38%)), Treatment 2 (-3.81 [95% CI -4.82 to -2.80];(-53%)), Treatment 3 (-4.49 [95% CI -5.62 to -3.57];(-69%)). As a result of this study, we conclude that supporting upper respiratory epithelia and reducing COX-mediated inflammation may be used to effectively treat common cold symptoms. Trial registration: ClinicalTrials.gov Identifier: NCT06106880 Posted 30/10/2023.

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Monoterpenes (thymol, carvacrol, menthol) and phenylpropanoids (eugenol and cinnamaldehyde) and their related derivatives are naturally occurring bioactive compounds found in essential oils (EOs) and have attracted considerable interest as anticancer agents; however, their direct therapeutic use in cancer treatment is often limited by factors such as low bioavailability, moderate potency, and lack of target specificity. Recent studies have demonstrated that rational structural modification of these EO scaffolds can substantially enhance their anticancer potential. This review critically evaluates the different structural modification strategies applied to EO components, including pharmacophore hybridization, heterocycle incorporation (e.g., triazoles, oxadiazoles, chalcones), esterification, halogenation, metal complexation, and nanoparticle conjugation. The review compares these approaches across the selected EO components, highlighting their impact on anticancer potency, and mechanistic relevance. However, the current evidence base is heterogeneous, with considerable variability in experimental conditions, selectivity assessments, and reliance on in vitro or in silico findings, which limits direct cross-study comparisons and translational interpretation. Overall, structural modification of EO components represents a promising strategy for generating novel anticancer lead compounds, but future progress will depend on standardized biological evaluation, rigorous in vivo validation, and comprehensive pharmacokinetic and toxicity profiling to realistically define their clinical potential.

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This review examines the pharmaceutical applications of essential oils (EOs) and terpenes, highlighting their dual role as therapeutic agents and natural penetration enhancers. These volatile, hydrophobic compounds have well-documented antimicrobial, antioxidant, and anti-inflammatory properties. However, their clinical potential is limited by poor water solubility, high volatility, and sensitivity to environmental factors, including light, heat, and oxygen. To address these challenges, various advanced delivery systems have been developed to enhance stability, bioavailability, and controlled release. These systems not only protect chemical integrity but also exploit these compounds' abilities to interact with lipid membranes, facilitating the transport of active compounds across biological barriers. Additionally, their inherent antimicrobial properties can contribute to the overall stability of formulations. The review critically examines the incorporation of terpenes and major essential oil (EO) components, such as limonene, linalool, eugenol, α-pinene, and menthol, into delivery systems, assessing their performance in enhancing drug permeability and targeting specific tissues. Current challenges and future directions in terpenes and EO-based delivery strategies are discussed, highlighting their promising role in developing multifunctional and efficient pharmaceutical formulations.

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The aim of this study was to assess the influence of eucalyptol and menthol on the cell viability, migration, and reactive oxygen species production of human gingival fibroblasts (GFs) in vitro. Three different concentrations of eucalyptol and menthol were prepared following ISO 10993-5 guidelines (1, 5, and 10 mM). GFs were isolated from extracted teeth from healthy donors. The following parameters were assessed: cell viability via MTT, Annexin-V-FITC and 7-AAD staining, and IC50 assays; cell migration via horizontal scratch wound assay; and cell oxidative stress via reactive oxygen species assay. Data were analyzed using one-way ANOVA and Tukey's post hoc test. Statistical significance was established at p < 0.05. Eucalyptol and Menthol exhibited high cytotoxicity on gingival fibroblasts, as evidenced by cytotoxicity assays. Eucalyptol showed lower levels of cytotoxicity than menthol, compared to the control group. The cytotoxicity of the tested substances increased in a concentration-dependent manner. The same occurred in a time-dependent manner, although even 10 min of exposure to the tested substances showed a high cytotoxicity to the GFs. Commercially available products for oral application with these substances in their composition should be tested for cytotoxicity before their use.

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