Umbelliferone (7-hydroxycoumarin): A non-toxic antidiarrheal and antiulcerogenic coumarin.

Gastrointestinal diseases are very common problems; available treatments are very limited and come with a range of side effects. Coumarins are an extensive class of phenolic compounds that can be found in plants, fungi and bacteria. The 7-hydroxycoumarin, also known as umbelliferone (UMB), is a compound that comes from coumarin and has been showing biological activities in other studies. As of this scenario, the present study was designed to evaluate the acute oral toxicity, mutagenic, antidiarrheal, anti-bacterial, and antiulcerogenic effects, and antioxidant capacity of UMB. An investigation was conducted through the hippocratic screening method and through histopathological analysis in animals to evaluate the effects of acute oral administration of a dose of 50, 100 and 200 mg/kg of UMB. A micronucleus test on peripheral blood of Swiss mice, which were orally treated with three doses (50, 100 and 200 mg/kg), was conducted to evaluate mutagenic activities. The antiulcerogenic activity was accomplished through the ethanol-induced damage method. Antidiarrheal activities were tested for inducing diarrhea with castor oil and evaluating intestinal transit duration; additionally, the antimicrobial effect against some enteropathogenic bacteria was analyzed. Finally, the antioxidant capability was determined by the capacity of the UMB sample to kidnap the stable radical 2,2-diphenyl-1-picrylhydrazyl. Of the evaluated doses, signs of toxicity after acute administration of the compound were not observed. UMB presented antiulcerogenic activity (100 and 200 mg/kg), which was explained because of its antioxidant capacity. A gastro protective effect was similar to the positive control, and the UMB was able to significantly reduce intestinal transit, and also diarrheal symptoms. Furthermore, UMB had an anti-bacterial effect with minimum inhibitory concentration fluctuating between 62.5 and 1000 µg/mL. Based on these findings, we can suggest that UMB has important biological activities in vivo and in vitro and is not toxic under the evaluated circumstances, which demonstrates its large potential for pharmacological use.

Development and in vivo evaluation of chitosan-gel containing Mitracarpus frigidus methanolic extract for vulvovaginal candidiasis treatment.

Vulvovaginal candidiasis (VVC) is characterized by inflammatory changes in the vaginal mucosa caused by abnormal colonization of Candida species. Traditional topical therapies using reference antifungal drugs usually present several issues and limitations for VVC treatment. Thus, the interest in new vaginal formulations, mainly those based on compounds from natural origin, has been growing over the last years. Methanolic extract from the plant species Mitracarpus frigidus (Willd. Ex Reem Schult.) K. Schum (MFM) has presented potential antifungal activity against C. albicans vaginal infection. Here, we aimed to develop and characterize a gynecological gel formulation based on chitosan containing MFM and to evaluate its anti-C. albicans effectiveness in the treatment of VVC. First, MFM was incorporated into a gel formulation based on chitosan in three final concentrations: 2.5 %, 5.0 %, and 10.0 %. Next, these gel formulations were subjected to stationary and oscillatory rheological tests. Finally, the gel was tested in an experimental VVC model. The rheological tests indicated pseudoplastic fluids, becoming more viscous and elastic with the increase of the extract concentration, indicating intermolecular interactions. Our in vivo analyses demonstrated a great reduction of vulvovaginal fungal burden and infection accompanied with the reduction of mucosal inflammation after MFM chitosan-gel treatment. The present findings open perspectives for the further use of the MFM-chitosan-gel formulation as a therapeutic alternative for VVC treatment.

Efficacy of curcumin in the treatment of experimental vulvovaginal candidiasis / Eficacia de la curcumina en el tratamiento de la candidiasis vulvovaginal experimental

Background: Candida albicans is the main agent that causes vulvovaginal candidiasis. Resistance among isolates to azole antifungal agents has been reported. Aims: Due to the well-known antifungal potential of curcumin, the purpose of this work was to evaluate the in vitro anticandidal activity of curcumin and its effect in the treatment of experimental vulvovaginal candidiasis. Methods: The anticandidal activity of curcumin was investigated against eight Candida strains by the broth microdilution assay, and its mechanism of action was evaluated by testing the binding to ergosterol. Then, the effect of curcumin in the treatment of vulvovaginal candidiasis was evaluated in an immunosuppressed, estrogen treated rat model. Results: Curcumin showed minimum inhibitory concentration values of 125-1000μg/ml, and the best result was observed against Candida glabrata. The compound was shown to be able to bind to the ergosterol present in the membrane, event that may be the mechanism of action. In addition, in the in vivo model of vulvovaginal candidiasis with C. albicans, treatments reduced the vaginal fungal burden in infected rats after seven days of treatment with different doses. Conclusions: Curcumin could be considered a promising effective antifungal agent in the treatment of vulvovaginal candidiasis

Antecedentes: Candida albicans es la principal causante de la candidiasis vulvovaginal y algunos aislamientos pueden presentar resistencia a los antifúngicos azólicos. Objetivos: Debido al conocido potencial antifúngico de la curcumina, el objetivo de este trabajo fue evaluar su actividad anti-Candidain vitro y su efecto en el tratamiento de la candidiasis vulvovaginal experimental. Métodos: La actividad anti-Candida de la curcumina se evaluó frente a ocho cepas de Candida mediante un ensayo de microdilución en caldo, y su mecanismo de acción se estudió por una prueba de unión a ergosterol. Posteriormente se evaluó el efecto de la curcumina en el tratamiento de la candidiasis vulvovaginal con un modelo de rata inmunosuprimida, tratada con estrógenos. Resultados: La curcumina mostró valores de concentración inhibitoria mínima de 125-1.000μg/ml, y el mejor resultado se observó frente a Candida glabrata. El compuesto demostró ser capaz de unirse al ergosterol de la membrana, lo que podría ser su mecanismo de acción. Además, en el modelo in vivo de candidiasis vulvovaginal con C. albicans, los tratamientos redujeron la carga fúngica vaginal en ratas infectadas después de siete días de tratamiento con diferentes dosis. Conclusiones: La curcumina podría considerarse un agente antifúngico eficaz prometedor en el tratamiento de la candidiasis vulvovaginal

Efficacy of curcumin in the treatment of experimental vulvovaginal candidiasis.

BACKGROUND: Candida albicans is the main agent that causes vulvovaginal candidiasis. Resistance among isolates to azole antifungal agents has been reported. AIMS: Due to the well-known antifungal potential of curcumin, the purpose of this work was to evaluate the in vitro anticandidal activity of curcumin and its effect in the treatment of experimental vulvovaginal candidiasis. METHODS: The anticandidal activity of curcumin was investigated against eight Candida strains by the broth microdilution assay, and its mechanism of action was evaluated by testing the binding to ergosterol. Then, the effect of curcumin in the treatment of vulvovaginal candidiasis was evaluated in an immunosuppressed, estrogen treated rat model. RESULTS: Curcumin showed minimum inhibitory concentration values of 125-1000µg/ml, and the best result was observed against Candida glabrata. The compound was shown to be able to bind to the ergosterol present in the membrane, event that may be the mechanism of action. In addition, in the in vivo model of vulvovaginal candidiasis with C. albicans, treatments reduced the vaginal fungal burden in infected rats after seven days of treatment with different doses. CONCLUSIONS: Curcumin could be considered a promising effective antifungal agent in the treatment of vulvovaginal candidiasis.