RESUMEN
Chronic pruritus is difficult to treat. Current treatment options are frequently ineffective and new therapeutic approaches are urgently needed. Avenanthramides are active substances in oats that exhibit anti-inflammatory effects. Their potential to interrupt pruritus mechanisms was investigated in this study. It was found that the synthetic analog dihydroavenanthramide D (DHAvD) can interact with the neurokinin-1 receptor (NK1R) and inhibit mast cell degranulation. DHAvD also affects inflammatory processes and reduces secretion of the cytokine interleukin-6. Our findings indicate that DHAvD may act as a NK1R inhibitor and could be a promising candidate for topical treatments of chronic pruritus.
Asunto(s)
Mastocitos/efectos de los fármacos , Prurito/tratamiento farmacológico , Receptores de Neuroquinina-1/metabolismo , ortoaminobenzoatos/uso terapéutico , Animales , Señalización del Calcio/efectos de los fármacos , Línea Celular , Enfermedad Crónica , Evaluación Preclínica de Medicamentos , Humanos , Ratas , Sustancia P , ortoaminobenzoatos/farmacologíaRESUMEN
During the past years, the topic sensitive skin became one of the most important fields in dermatology. The tremendous interest is based on several studies showing that about 50% of the population declares to have sensitive skin. The human thermoreceptor hTRPV1 was previously identified to contribute to this skin condition while facilitating neurogenic inflammation leading to hyperalgesia. Furthermore, skin sensitivity towards capsaicin, a natural activator of TRPV1, was shown to correlate with sensitive skin. In a screening campaign based on recombinant HEK293-cells stably transfected with hTRPV1, the selective antagonist trans-4-tert-butylcyclohexanol was identified. This antagonist is able to inhibit capsaicin-induced hTRPV1 activation with an IC(50) value of 34 ± 5 µm tested in HEK293-cells as well as in electrophysiological recordings performed in oocytes expressing hTRPV1. Strikingly, in a clinical study with 30 women using topical treatment with o/w emulsions containing 31.6 ppm capsaicin, we were able to show that 0.4% of this inhibitor significantly reduces capsaicin-induced burning (P < 0.0001) in vivo. Thus trans-4-tert-butylcyclohexanol has the potential as a novel bioactive for the treatment of sensitive skin.
Asunto(s)
Ciclohexanoles/farmacología , Ciclohexanoles/uso terapéutico , Moduladores del Transporte de Membrana/farmacología , Moduladores del Transporte de Membrana/uso terapéutico , Trastornos de la Sensación/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológico , Canales Catiónicos TRPV/antagonistas & inhibidores , Adulto , Animales , Compuestos de Boro/farmacología , Señalización del Calcio/efectos de los fármacos , Capsaicina/farmacología , Línea Celular , Femenino , Humanos , Activación del Canal Iónico/efectos de los fármacos , Oocitos/efectos de los fármacos , Canales Catiónicos TRPV/agonistas , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo , Transfección , Xenopus laevisRESUMEN
The glycosylated pyrrolizidine alkaloid, thesinine-4'-O-beta-D-glucoside, has been isolated from the aqueous methanol extract of dried, defatted seeds of Borago officinalis (Boraginaceae). The structure was established by means of spectroscopic and chemical analysis.