Clinical Effectiveness and Tolerability of 2% Menthol in Musculoskeletal Pain : A Pilot Observational Real-world Evidence Study

Objective : To determine the efficacy and safety of 2% menthol in the management of musculoskeletal pain. Materials and Methods : 81 patients above the age of 18 years of either sex with any musculoskeletal pain were included in the study. Subjects were instructed to apply 2% menthol gel twice daily to the affected area for 7 to 10 days. A Visual Analog Scale (VAS) was used to assess the severity of the initial pain. Moreover, the level of muscle soreness on a 7-point Likert scale was also evaluated. The patients were assessed before the treatment and 7 to 10 days after the initiation of the treatment. Results : The VAS scores for pain significantly improved (P< 0.0001) in subjects after completion of the treatment. There was a 70% improvement (7.67 � 1.04 before treatment to 2.30 � 0.56 after treatment) in the VAS scores compared to baseline, and the mean Likert scale of muscle soreness was 2.04 � 0.25 at the end of the treatment. Moreover, no significant adverse events were observed in the patients during the study. Conclusion : The study showed that 2% menthol effectively improves musculoskeletal pain

Role of corneal cold thermoreceptors in the occurrence and development of dry eye / 中华实验眼科杂志

Dry eye is a multifactorial disease caused by changes in tear quality, volume and dynamics.Disturbance of tear film as the main character is accompanied by discomfort, visual disorder, and damage to the ocular surface and nerves.Cold thermoreceptors existing on the ocular surface are sensitive to alterations in corneal temperature and tear osmolality.They can give rise to the sensations of cold and pain, and regulate tear secretion, and are considered to be associated with the clinical manifestations of dry eye in some ways.This article reviewed the progress of corneal cold thermoreceptors in the regulation of corneal sensation and tear secretion, the related factors of corneal sensory regulation, and the clinical applications of TRPM8-related drugs, so as to provide ideas for the treatment of dry eye.

Pharmacological effects of menthol and its present development and application / 中国药房

Menthol is the main component of mint volatile oil and a monoterpenoid organic compound. This article systematically summarizes the pharmacological effects， present development and application status of menthol. It is found that menthol can protect the central nervous system through acting on the transient receptor potential （TRP） channel subfamily M member 8， 5-hydroxytryptamine system， γ -aminobutyric acid system， etc. Menthol can regulate body temperature through temperature adjustment， relieving heat stress， and other means. It can play an anti-inflammatory role by regulating the production and release of inflammatory mediators such as prostaglandin E2 and leukotriene B4， and exert anti-inflammatory effects through cellular immune effect mediated by TRP channel. It can play analgesic role by activating classic pain perception targets and enhancing inhibitory synaptic transmission. It can promote transdermal absorption by destroying the stratum corneum. It can exert anti-tumor effects by regulating tumor cell proliferation， apoptosis， and adhesion pathways. Menthol can be used as a medicinal excipient for correcting the taste of drugs； it can also serve as an active ingredient and play an important pharmacological role in the treatment of disease， with potential development value.

Effect of nanoparticles of different stiffness combined with menthol/curcumol on mechanical properties of bEnd.3 cells / 中国中药杂志

This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.

Extraction and Characterisation of Flavoured Tobacco by GC-MS Studies and Validation of Results by GC-FID to Investigate Hazardous Flavour Ingredients

Flavoured tobacco is mainly consumed in India and neighbouring countries like Pakistan, Afghanistan, and Nepal and the hazards are known. Considering the need to identify such flavouring ingredients and a simple analytical method was required to quantify such favouring ingredients and hazardous / allergens, we selected top brands available in India for investigation. We simply extracted the ingredients by triturating with Diethyl Ether, evaporating solvent ether and reconstituting the extract in Acetone & Ethanol for GC-MS & GC-FID work respectively. The flavour ingredients were identified, and hazardous ingredients, viz. Diethyl Phthalate was identified. It was found around 2.5% to 3.0%. The GC-MS method was validated with GC-FID analysis with Linearity, LOD & LOQ study.

Effects of L-menthol on suppression of gastric peristalsis during upper gastrointestinal endoscopy and the influencing factors / 中华消化内镜杂志

Objective:To evaluate the effects of single spay of L-menthol (NPO-11) on suppressing gastric peristalsis during upper gastrointestinal endoscopy and the influencing factor.Methods:This study was a multicenter, randomized, double-blind, placebo-parallel controlled study. The eligible patients were randomly divided into two groups by randomized blocks. Patients received local spray of either NPO-11 (160 mg L-menthol) or placebo 20 mL during upper gastrointestinal endoscopy. The gastric peristalsis was recorded and evaluated before, 2 minutes after and at the end of endoscopy. The complexity of the procedure was evaluated by the researchers. The influencing factors for antiperistaltic effect of NPO-11 were analyzed.Results:A total of 220 patients were enrolled from five research centers. There were 109 cases in the NPO-11 group and 111 cases in the placebo group. The baseline data of the two groups were similar and comparable. The proportion of patients with grade 1 peristalsis at 2 minutes after the treatment and at the end of endoscopy was significantly higher in the NPO-11 group than that in the placebo group [40.37% (44/109) VS 16.22% (18/111), χ2=15.93, P<0.001]. Compared with the placebo group, the proportions of weak peristalsis (grade 1 and 2) were higher in the NPO-11 group at 2 minutes after the treatment [67.89% (74/109) VS 46.85% (52/111)] and at the end of endoscopy [79.82% (87/109) VS 48.65% (54/111)]. Subgroup analysis showed that the inhibitory effect of NPO-11 on gastric peristalsis was more significant in Helicobacter pylori antibody positive group. Conclusion:Local spray of NPO-11 can effectively inhibit gastric peristalsis during upper gastrointestinal endoscopy, and its effect is more significant in Helicobacter pylori antibody positive group. It could be recommended for no obvious adverse reactions , its safety, and the convenient procedure.

Establishment of gas chromatography for content determination of five volatile components in Qingxuan pills / 中国药房

OBJECTIVE To estab lish a meth od for the determination of 5 volatile components as menthone ，menthol， pulegone，piperitone and ligustilide in Qingxuan pills. METHODS Seven batches of Qingxuan pills were taken as test samples and determined by gas chromatography. The gas chromatographic column was DB- 5 sillica capillary column ，the carrier gas was nitrogen，the inlet temperature was 200 ℃. The sample size was 1 μL，and the split ratio was 10 ∶ 1. The temperature was programmed（the initial temperature was kept at 100 ℃ for 2 min，and then raised to 220 ℃ at 5 ℃/min for 2 min），and the temperature of the flame ionization detector was 250 ℃. RESULTS The chromatographic peaks of menthone ，menthol，pulegone， piperitone and ligustilide reached the baseline separation ；the linear ranges of the five components were 0.008-0.388，0.010-0.527， 0.006-0.327，0.006-0.312，0.053-2.672 mg/mL（all r＞0.999 0）；the average recoveries were 96.33％（RSD＝1.23％，n＝6）， 96.92％（RSD＝1.38％，n＝6），97.53％（RSD＝1.81％，n＝6），96.80％（RSD＝1.89％，n＝6）and 95.61％（RSD＝0.77％， n＝6）；the contents of the five components were 0.009-0.070，0.040-0.157，0.017-0.150，0.008-0.049 and 0.144-0.932 mg/g， respectively. CONCLUSIONS The gas chromatography method established in this study is simple and accurate ，which can simultaneously determine the contents of five volatile components in Qingxuan pills .

Seasonal variation in essential oil content and chemical profile of mint in southeast of Brazil / Variação sazonal no teor e perfil químico do óleo essencial de menta no sudeste do Brasil

ABSTRACT: This study evaluated the influence of seasonality in essential oil (EO) chemical composition of Mentha x piperita L. and Mentha viridis L. grown in southeast of Brazil. Leaves were collected from November 2011 until August 2013, in the middle of the following seasons: Spring (November), Summer (February), Autumn (May) and Winter (August). EO extraction was carried out by hydrodistillation in Clevenger apparatus for 1 hour. Chemical composition of EO was analyzed by GC-FID and GC-MS. The EO content and its chemical composition were influenced by seasonality in both species. The highest EO content was obtained for M. x piperita during spring (4.26%) and for M. viridis during spring (3.30%) and summer (3.70%). Mentha x piperita increased menthol (16.31 to 41.26%), neomenthol (3.02 to 6.39%) and menthone (5.56 to 41.58%) contents during spring and summer, respectively. Whereas, M. viridis EO content did not show a quality response pattern in relation to seasonality. Therefore, harvest time for M. x piperita is recommended during spring, and for M. viridis is recommended during spring and summer.

RESUMO: O estudo teve como objetivo avaliar a influência da sazonalidade na composição química do óleo essencial (OE) de Mentha x piperita L. e Mentha viridis L. cultivadas no sudeste do Brasil. As folhas foram coletadas de novembro de 2011 até agosto de 2013, em meados das seguintes estações: primavera (novembro), verão (fevereiro), outono (maio) e inverno (agosto). A extração do OE foi realizada por hidrodestilação em aparelho de Clevenger por uma hora. A composição química do EO foi analisada por GC-FID and GC-MS. O teor de OE e sua composição química foram influenciados pela sazonalidade em ambas as espécies. O maior teor de OE foi obtido para M. x piperita na primavera (4,26%) e para M. viridis na primavera (3,30%) e verão (3,70%). Mentha x piperita aumentou o conteúdo de mentol (16,31 a 41,26%), neomentol (3,02 a 6,39%) e mentona (5,56 a 41,58%) durante a primavera e o verão, respectivamente. Já o conteúdo de OE de M. viridis não apresentou padrão de resposta de qualidade em relação à sazonalidade. Portanto, a colheita para M. x piperita é recomendada durante a primavera, e para M. viridis é recomendada durante a primavera e verão.

Craving por mentolados: a propósito de un caso

Se describe un caso de craving por dulces mentolados, una paciente de 53 arios con cuadro de consumo excesivo de dulces mentolados (100 unidades/día). Ingresó con el antecedente de artritis reumatoide, con obesidad, en estado de ansiedad asociado con onicofagia y pellizcos de la piel. Se descartó la organicidad mediante paraclínicos y se le dio asistencia hospitalaria. Al alta, la paciente estaba estable; sin embargo, por progresión del dolor por la enfermedad reumática, ha sufrido síntomas depresivos, por lo que ha requerido ajuste de la medicación. Conclusiones: El food craving y la ansiedad presentan similitudes fisiopatológicas. Las mentas tienen distintos mecanismos o modos en que pueden contrarrestar o controlar estos síntomas, entre los que está el aumento de serotonina, la unión a receptores GABA-A y la estimulación del receptor nicotínico en las células nerviosas.

We describe a case of craving for menthol sweets in a 53-year-old woman with excessive consumption of menthol sweets (100 units/day). She was admitted with a history of rheumatoid arthritis, obesity, anxiety associated with onychophagia and pinching of the skin. Organic disorders were ruled out with paraclinical tests and in-hospital treatment was administered. At discharge, the patient's condition was stable, but because of exacerbated pain due to the rheumatological disease, she presented depressive symptoms, requiring her medication to be adjusted. Conclusions: The "food craving" and anxiety present pathophysiological similarities. Mints have different mechanisms or ways in which they can counteract or control these symptoms, including an increase in serotonin, binding to GABA-A receptors and stimulation of the nicotinic receptor in nerve cells.

Desarrollo y validación de un método de cromatografía gaseosa para la determinación de mentol, salicilato de metilo, timol y ácido benzoico en solución antiséptica / Development and validation of a gas chromatographic method for the determination of menthol, methyl salicylate, thymol, and benzoic acid in antiseptic solution

RESUMEN Se desarrolló y validó un método por cromatografía gaseosa para la cuantificación simultánea de mentol (MT), salicilato de metilo (SM), timol (TM) y ácido benzoico (AB) en una solución antiséptica bucal. Se utilizó una columna DB-WAX y dietilenglicol como estándar interno. Se determinó la linealidad en un intervalo de concentraciones de 64,00 a 96,00 µg/mL (MT), 80,00 a 120,00 µg/mL (SM), 96,00 a 144,00 µg/mL (TM) y 48,00 a 72,00 µg/mL (AB), obteniendo coeficientes de correlación superiores a 0,999, y coeficientes de variación de los factores de respuestas de 1,18, 1,95, 3,52 y 1,48%, respectivamente. Se establecieron límites de detección de 0,51; 1,14; 3,34 y 1,402 ng/mL para el MT, SM, TM y AB, respectivamente, mientras los límites de cuantificación fueron de 1,45, 3, 43, 9, 73 y 4, 36 ng/mL en cada caso. Los porcentajes de recuperación fueron de 100,03, 99, 31, 99, 92 y 100,12; con coeficientes de variación de 0,42, 0,79, 0,66 y 0,76% para cada caso. El método fue lineal, exacto, preciso y selectivo para la determinación de los analitos en el control de calidad.

SUMMARY A method was developed and validated by gas chromatography for the simultaneous quantification of menthol (MT), methyl salicylate (SM), thymol (TM) and benzoic acid (AB) in an oral antiseptic solution. A DB-WAX column and diethylene glycol was used as internal standard. Linearity was determined in a concentration range of 64.00 to 96.00 µg/mL (MT), 80.00 to 120.00 µg/mL (SM), 96.00 to 144.00 µg/mL (TM) and 48.00 to 72.00 µg/mL (AB) achieving correlation coefficients greater than 0.999, and coefficients of variation of the response factors of 1.18, 1.95, 3.52 and 1.48%, respectively. Detection limits were established: 0.51, 1.14, 3.34 and 1.402 ng/mL for MT, SM, TM, and AB, respectively, while the quantification limits were 1.45, 3.43, 9.73 and 4.36 ng/mL in each case. Recovery percentages were 100.03, 99.31, 99.92 and 100.12; with coefficients of variation of 0.42, 0.79, 0.66 and 0.76% for each case. The method was linear, accurate, precise, and selective for the determination of analytes in quality control.

Menthol enhances interleukin-13-induced synthesis and secretion of mucin 5AC in human bronchial epithelial cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of interleukin (IL) -13 combined with cold stimulation on synthesis and secretion of mucin (MUC) 5AC in human bronchial epithelial cell line 16HBE and explore the role of transient receptor potential 8 (TRPM8) and anti-apoptotic factor B-cell lymphoblast-2 (Bcl-2) in this process.@*METHODS@#16HBE cells were stimulated with 10 ng/mL IL-13, 1 mmol/L menthol, or both (1 mmol/L menthol was added after 6 days of IL-13 stimulation), and the changes in the expression of MUC5AC, intracellular Ca@*RESULTS@#The mRNA and protein expressions of MUC5AC increased significantly in 16HBE cells following stimulation with IL-13, menthol, and both (@*CONCLUSIONS@#Menthol combined with IL-13 produces a synergistic effect to promote the synthesis and secretion of MUC5AC in 16HBE cells possibly by activating TRPM8 receptor to upregulate the expression of Bcl-2.

Azone combined with menthol has penetration-promoting effect on 5-fluorouracil / 中国临床药理学与治疗学

AIM: To compare the effect of azone and menthol by using the 5-fluorouracil (5-FU) as drug model, and explore the mix effect of the two transdermal enhancers. METHODS: The test acts on the self-made instrument. After the test, calculate the total amount of the drug which has permeate through the skin was calculated and the mixed effect of azone and menthol was estimated by multiple quantity method.RESULTS: Both azone and menthol of concentrations of 0.25%, 0.50%, 1.00% and 2.00% had significant penetration promoting effect on 5-fluorouracil, which were significantly different from the control group (P<0.01). No synergistic effect was detected when evaluating the combined effect of the two drugs by multiple dose method. CONCLUSION: Both azone and menthol have promotion effect on 5-fluorouracil, but the combined use of the two drugs of same concentration show no synergistic effect.

Package of menthol measures for thirst relief: a randomized clinical study / Paquete de medidas mentoladas para el alivio de lased: estudio clínico aleatorizado / Pacote de medidas mentoladas para o alívio da sede: estudo clínico randomizado

ABSTRACT Objective: To evaluate the effectiveness of the menthol package (lip hydration and ice popsicles) compared to a package of non-menthol measures (lip hydration and ice popsicles) as a way to relieve thirst in patients in the Anesthetic Recovery Room. Method: Randomized and parallel trial study, with 120 patients randomized patients in an experimental group - menthol measurements (n=59) and control group - measures without menthol (n = 61). Results: There was a significant (p<0.05) decrease in intensity, hydration, dryness and taste in the oral cavity between the three moments of assessment/intervention in the two groups. The difference was significant in the experimental group for thirst intensity at the second assessment/intervention point (p<0.05) after a single administration of the menthol package. Conclusion: There was a reduction in thirst intensity in both groups. Patients who received menthol packages showed a significant decrease in intensity after a single evaluation/intervention time. NCT: 02869139.

RESUMEN Objetivo: Evaluar la efectividad del paquete de medidas mentoladas (hidratación labial y picolé de hielo) comparado a un paquete de medidas no mentoladas (hidratación labial y picolé de hielo) como un método de alivio de la sed en pacientes en la Sala de Recuperación Post-Anestésica. Método: En un ensayo clínico aleatorizado, paralelo, 120 pacientes aleatorizados en un grupo experimental - medidas mentoladas (n=59) y un grupo control - medidas sin el mentol (n=61). Resultados: Hubo una disminución significativa (p<0,05) sobre la intensidad, hidratación, sequedad y gusto en la cavidad oral entre los tres momentos de evaluación/intervención en los dos grupos, indistintamente. La diferencia fue significativa en el grupo experimental para la intensidad de la sed en el segundo momento de la evaluación/intervención (p<0,05) después de una única administración del paquete de medidas mentoladas. Conclusión: Se encontró una reducción de la intensidad de la sed en los dos grupos. Los pacientes que recibieron las medidas mentoladas presentaron una disminución significativa de la intensidad después de un único momento de evaluación/intervención. NCT: 02869139.

RESUMO Objetivo: Avaliar a efetividade do pacote de medidas mentoladas (hidratação labial e picolé de gelo) comparado a um pacote de medidas não mentoladas (hidratação labial e picolé de gelo) como método de alívio da sede em pacientes na Sala de Recuperação Anestésica. Método: Ensaio clínico randomizado, paralelo, 120 pacientes aleatorizados em grupo experimental - medidas mentoladas (n=59) e grupo controle - medidas sem o mentol (n=61). Resultados: Houve diminuição significativa (p<0,05) sobre a intensidade, hidratação, secura e gosto na cavidade oral entre os três momentos de avaliação/intervenção nos dois grupos indistintamente. A diferença foi significativa no grupo experimental para intensidade da sede no segundo momento de avaliação/intervenção (p<0,05) após uma única administração do pacote de medidas mentoladas. Conclusão: Houve redução da intensidade da sede nos dois grupos. Os pacientes que receberam as medidas mentoladas apresentaram diminuição significativa da intensidade após um único momento de avaliação/intervenção. A NCT: 02869139.

Goma de mascar mentolada no manejo da sede pré-operatória: ensaio clínico randomizado / Menthol chewing gum on preoperative thirst management: randomized clinical trial / Goma de mascar mentolada en el manejo de la sed preoperatoria: ensayo clínico aleatorizado

Objetivo avaliar a efetividade da goma de mascar mentolada em aliviar a intensidade e o desconforto da sede do paciente cirúrgico no período pré-operatório. Método ensaio clínico controlado randomizado, com 102 pacientes em período pré-operatório, aleatorizados em grupo-controle, com cuidado usual, e grupo experimental, que recebeu goma de mascar mentolada, a variável de tratamento do estudo. O desfecho clínico primário foi a variação da intensidade da sede, avaliada pela Escala Verbal Numérica, e o secundário, a variação do desconforto da sede, avaliada pela Escala de Desconforto da Sede Perioperatória. Teste de Mann-Whitney foi usado para comparar as medidas entre os grupos. Nível de significância adotado de 0,05. Resultados a goma de mascar mentolada reduziu significativamente a intensidade (p<0,001), com d de Cohen de efeito médio, e o desconforto da sede (p<0,001), com d de Cohen de efeito grande. Conclusão a goma de mascar mentolada mostrou-se efetiva na redução da intensidade e do desconforto da sede pré-operatória. A estratégia mostrou-se uma opção inovadora, viável e segura no uso para o paciente cirúrgico, no manejo da sede pré-operatória, em cirurgias eletivas. NCT: 03200197.

Objective to evaluate the effectiveness of menthol chewing gum, in the relief of the intensity and discomfort of the surgical patient's thirst in the preoperative period. Method a randomized controlled trial, with 102 patients in the preoperative period, randomized in a control group, with usual care, and an experimental group, which received menthol gum, which was the study treatment variable. The primary clinical outcome was the variation in thirst intensity, evaluated by the Numeral Verbal Scale, and the secondary, the variation of the discomfort of thirst, evaluated by the Perioperative Thirst Discomfort Scale. Mann-Whitney test was used to compare measures between groups. The significance level adopted was of 0.05. Results menthol chewing gum significantly reduced the intensity (p <0.001), with Cohen's medium-effect d, and thirst discomfort (p <0.001), with a large-effect Cohen's d. Conclusion menthol chewing gum was effective in reducing the intensity and discomfort of preoperative thirst. The strategy proved to be an innovative, feasible and safe option in the use for the surgical patient, in the management of the preoperative thirst, in elective surgeries. NCT: 03200197.

Objetivo evaluar la efectividad de la goma de mascar mentolada en aliviar la intensidad y la incomodidad de la sed del paciente quirúrgico en el período preoperatorio. Método ensayo clínico controlado aleatorizado, con 102 pacientes en período preoperatorio, aleatorizados en grupo control, con cuidado usual, y grupo experimental, que recibió goma de mascar mentolada, la variable de tratamiento del estudio. El resultado clínico primario fue la variación de la intensidad de la sed, evaluada por la Escala Verbal Numérica, y el secundario, la variación de la incomodidad de la sed, evaluada por la Escala de Desconocimiento de la Sede Perioperatoria. La prueba de Mann-Whitney fue utilizada para comparar las medidas entre los grupos. Nivel de significancia adoptado de 0,05. Resultados la goma de mascar mentolada redujo significativamente la intensidad (p <0,001), con d de Cohen de efecto promedio, y el malestar de la sed (p <0,001), con d de Cohen de efecto grande. Conclusión la goma de mascar mentolada se mostró efectiva en la reducción de la intensidad y de la incomodidad de la sed preoperatoria. La estrategia se mostró una opción innovadora, viable y segura en el uso para el paciente quirúrgico, en el manejo de la sed preoperatoria, en cirugías electivas. NCT: 03200197.

Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy

Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood-brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers. Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and glioma-targeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs. The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of menthol-modified casein nanoparticles (M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-M-CA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining of the organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.

Effect of Menthol on Proliferation, Migration and Expressions of IL-8, CXCL-12 and VEGF in Hepatoma HepG2 Cells / 中国实验方剂学杂志

Objective: To study the effect of menthol on proliferation, migration and expressions of interleukin-8(IL-8), C-X-C motif chemokine-12(CXCL-12) and vascular endothelial growth factor(VEGF) in hepatoma HepG2 cells in vitro, in order to elucidate the anti-liver cancer activity of menthol and relevant mechanisms. Method: Different concentrations of menthol (25, 50, 100, 200 μmol·L-1) and blank group were applied to Hepatoma HepG2 cells. Cell counting kit-8(CCK-8) and EDU were used to detect the proliferation effect of menthol on HepG2 cell. Transwell experiment was used to detect the migration effect of menthol on HepG2 cell. Real-time fluorescent quantitative polymerase chain reaction technique was used to detect the inflammatory chemokines IL-8 and CXCL-12 mRNA expression levels in HepG2 cell. Western blot was used to detect the expression level of VEGF in HepG2 cells treated with menthol. Result: Compare with the blank group, menthol (25, 50, 100, 200 μmol·L-1) significantly inhibited proliferation and migration of HepG2 cells in vitro. When the concentration of menthol was 100 μmol·L-1 microns, the inhibitory effect was significant (P-1) significantly inhibited the expression levels of IL-8, CXCL-12 mRNA and VEGF protein in HepG2 cells (PConclusion: Menthol has an inhibitory effect on the proliferation and migration of hepatoma HepG2 cells in vitro, and the potential anti-liver cancer mechanism might be related to the inhibition of IL-8, CXCL-12 and VEGF expressions in the cells. This conclusion provides the experimental basis for elucidating the effect of menthol against liver cancer.

O uso do picolé mentolado no manejo da sede do paciente idoso no pósoperatório imediato: ensaio clínico randomizado / The use of mentholated popsicle to manage the elderly patient´s thirst in the immediate postoperative period: randomized clinical trial

Os mecanismos fisiológicos de detecção e controle da sede no paciente cirúrgico idoso ocorrem de forma diferenciada do que em adultos e crianças o que justifica o investimento na condução de estudos sobre estratégias que podem proporcionar alívio deste sintoma com o uso de temperatura fria e volume pequeno. O objetivo do estudo foi comparar a intensidade e o desconforto da sede de pacientes idosos que degustaram o picolé mentolado com a sede de pacientes idosos que receberam o cuidado usual, no pós-operatório imediato. Trata-se de ensaio clínico randomizado em paralelo com dois grupos, realizado em sala de recuperação pós-anestésica de hospital público de ensino no sul do Brasil. A amostra foi composta de 50 pacientes idosos em pós-operatório imediato, os quais foram alocados em dois grupos, sendo 25 no grupo controle e 25 no grupo experimental, sem perda de seguimento. Os critérios de inclusão foram: pacientes com idade >= 60 anos; estar em jejum; verbalizar sede e ter sido aprovado na avaliação do Protocolo de Segurança no Manejo da Sede. Os pacientes com restrições à ingesta ou deglutição, bem como os que autorreferiram alergia à menta, foram excluídos. Os pacientes alocados no grupo controle receberam o cuidado usual de rotina da instituição, onde o estudo foi conduzido, que consiste na manutenção do jejum. Já os pacientes alocados no grupo experimental receberam um picolé mentolado de 20 ml. Os desfechos primários de interesse foram a intensidade e o desconforto da sede, sendo que ambos foram avaliados inicialmente (T0) e novamente (T1) após 20 minutos da intervenção ou cuidado usual. A intensidade da sede foi mensurada por meio da Escala Numérica (zero significa nenhuma sede e 10 a maior sede já vivenciada pelo paciente), e o desconforto da sede pela Escala de Desconforto da Sede Perioperatória (pontuação de zero a 14 pontos, sendo zero a ausência de desconforto e 14 corresponde ao desconforto mais intenso relacionado à sede). A mediana da intensidade e do desconforto da sede inicial (T0) foi de 6,0 para os participantes alocados no grupo experimental, e 5,0 para a intensidade e 6,0 para o desconforto da sede para os participantes alocados no grupo controle. Para a comparação das mudanças nos escores da Escala Numérica e da Escala de Desconforto da Sede Perioperatória entre o grupo experimental e o grupo controle (valor final menos valor inicial), o teste de Mann-Whitney foi empregado para diferenças de medianas. Os resultados do ensaio clínico randomizado demonstraram que houve diminuição estatisticamente significante na intensidade (p<0,001) e no desconforto da sede (p<0,001) dos pacientes cirúrgicos idosos, após vinte minutos da degustação do picolé mentolado quando comparados à intensidade e desconforto da sede dos pacientes que receberam o cuidado usual, no pósoperatório imediato. Considerando a escassez de evidências sobre estratégias para manejo da sede do paciente cirúrgico idoso, o picolé mentolado é uma estratégia inovadora e segura, podendo se tornar método de escolha para uso na prática clínica

Physiological mechanisms of detection and control of thirst in the elderly surgical patient occur differently than in adults and children, which justifies the investment in conducting studies on strategies that can provide relief of this symptom with use of cold temperature and small volume. The aim of the study was to compare thirst intensity and discomfort of elderly patients who savoured mentholated popsicle with thirst of elderly patients who received the usual care in the immediate postoperative period. This is a randomized controlled clinical trial in parallel with two groups, conducted in a post anesthesia care unit of a public teaching hospital in southern Brazil. The sample consisted of 50 elderly patients in the immediate postoperative period, who were allocated in two groups, 25 in the control and 25 in the experimental group, without follow-up losses. Inclusion criteria were: patients aged >= 60 years; being fasting; verbalize thirst and having been approved in the assessment of Safety Protocol of Thirst Management. Patients with restrictions to ingestion or swallowing, as well as those who self-referred peppermint allergy, were excluded. Patients assigned to the control group received usual routine care of the institution where the study was conducted, which consists in maintenance of fasting. Patients assigned to the experimental group received a 20 ml mentholated popsicle. Primary outcomes of interest were thirst intensity and discomfort, both of which were assessed initially (T0) and again (T1) after 20 minutes of the intervention or usual care. Thirst intensity was measured using a Numerical Scale (zero means no thirst and 10 the greatest thirst ever experienced by patient), and thirst discomfort by Perioperative Thirst Discomfort Scale (score of zero to 14 points, being zero the absence of discomfort and 14 corresponds to the most intense discomfort related to thirst). Median of initial thirst intensity and discomfort (T0) was 6.0 for the participants assigned to the experimental group, 5.0 for thirst intensity and 6.0 for thirst discomfort for the participants assigned to the control group. Mann-Whitney test was used evaluating differences in medians, comparing changes in Numerical Scale and in Perioperative Thirst Discomfort Scale between the experimental group and the control group (final value minus initial value). Results of the randomized clinical trial demonstrated that there was a statistically significant decrease in thirst intensity (p <0.001) and discomfort (p <0.001) of elderly surgical patients, after twenty minutes of tasting the mentholated popsicle when compared to thirst intensity and discomfort of the patients who received the usual care, in the immediate postoperative period. Considering the shortage of evidence on strategies for thirst management of elderly surgical patient, mentholated popsicle is an innovative and safe strategy, and may become a method of choice for use in clinical practice

Action of Essential Oils on Sprouting of Non-Dormant Potato Tubers

ABSTRACT The breakdown of dormancy and early sprouting is one of the main causes of losses of stored potatoes. Sprouting control becomes important especially when tubers are submitted to long-term storage for further processing by the potato industry. The objective of this work is to evaluate the effect of organic sprout inhibitors, eugenol and menthol essential oils, on the suppression of growth on non-dormant 'Asterix' tubers stored at 8 °C. Administration of eugenol and menthol essential oils reduced the number and the length of sprouts during cold storage up to fifty days. Nevertheless, the essential oils stimulated the break of bud apical dominance, stimulating auxiliary buds growth. The effect of the oils was restricted to inducing necrosis of superficial sprout cells without any apparent effect on the skin periderm structure. Repeated applications of oils are necessary to prolong the inhibitory effects of the essential oils on sprouts growth.

Effect of paeoniflorin and menthol on membrane fluidity, Na⁺-K⁺-ATPase activity and Ca²⁺-ATPase activity during transport of puerarin in Calu-3 cell / 中国中药杂志

The aim of this research is to investigate the effects of paeoniflorin and menthol on the physiological function of Calu-3 cell membrane during the transport of puerarin. Calu-3 cell was used as the cell model to simulate nasal mucosa tissues, and the cell membrane fluidity, Na⁺-K⁺-ATPase activity and Ca²⁺-ATPase activity were detected by fluorescence recovery after photobleaching(FRAP) and ultramicro enzyme activity testing, in order to explore the mechanism of compatible drugs on promoting puerarin transport. The results showed that when puerarin associated with low, middle and high concentration of menthol or both paeoniflorin and menthol, the fluorescence recovery rate was increased significantly, while Na⁺-K⁺-ATPase activity had no significant change and Ca²⁺-ATPase activity was enhanced significantly as compared with puerarin alone. Therefore, it was concluded that menthol had the abilit of promoting the transport and the mechanism might be related to increasing membrane fluidity and activating Ca²⁺-ATPase.

Application of borneol and menthol in promoting nanopreparations across physiological barriers / 中草药

In this review, the ability of borneol and menthol as the common penetration enhancers in traditional Chinese medicines was summarized, and the effect of borneol and menthol on the ability of nanopreparations across the main physiological barriers of the human body promoting drug absorption or increasing the distribution of drugs was also reviewed, which aims to provide reference for promoting the treatment effect of nanopreparations through the combination of traditional Chinese medicine and modern preparation technology.