RESUMEN
A number of studies confirmed the involvement of transient receptor potential vanilloid (TRPV) and acid-sensing (ASIC) ion channels in the physiological processes associated with the development of anxiety disorders. This makes their ligands new potential anxiolytic agents. We examined the efficacy of two peptides from the sea anemone Heteractis crispa, Hcr 1b-2 and HCRG21, affecting ASIC1a and TRPV1 channels, respectively, in the open field and elevated plus maze tests. According to the obtained data, HCRG21 significantly decreases both the level of anxiety and stimulates the activity of animals at doses of 0.01-1 mg/kg, whereas Hcr 1b-2 has a weak anxiolytic effect only at a dose of 0.1 mg/kg. The pharmacodynamic study showed that the HCRG21 has an anxiolytic effect for 2 h, and its effectiveness is higher than that of the reference drug.
Asunto(s)
Ansiolíticos , Anémonas de Mar , Canales Iónicos Sensibles al Ácido , Animales , Ansiolíticos/farmacología , Péptidos/farmacología , Canales Catiónicos TRPVRESUMEN
The ion channel TRPV1, which is one of the most important integrators of pain and inflammatory stimuli, is considered a promising therapeutic target in the treatment of pain conditions. In this work, we performed a comparative study of the analgesic effect in the "hot plate" test of recombinant analogues of Kunitz-type peptides from the sea anemone Heteractis crispa venom: APHC1-modulator of TRPV1 and HCRG21-a full blocker of TRPV1. As a result of biological tests, it was shown that the full blocker HCRG21, despite the higher value of 50% effective concentration of TRPV1 inhibition, had an equal analgesic ability with the APHC1 upon intramuscular administration and retained it for 13 h of observation. The analgesic effect of APHC1 at a dose of 0.1 mg/kg when administered intramuscularly developed very quickly in 5 min but lasted 3 h. The differences in the pharmacodynamic profile of the peptides are in good agreement with different mechanisms of binding to TRPV1.
Asunto(s)
Analgésicos/farmacología , Venenos de Cnidarios/farmacología , Dolor/tratamiento farmacológico , Péptidos/farmacología , Canales Catiónicos TRPV/antagonistas & inhibidores , Secuencia de Aminoácidos , Analgésicos/administración & dosificación , Animales , Venenos de Cnidarios/administración & dosificación , Modelos Animales de Enfermedad , Calor , Inyecciones Intramusculares , Ratones , Ratones Endogámicos ICR , Dolor/metabolismo , Péptidos/administración & dosificación , Anémonas de Mar , Homología de SecuenciaRESUMEN
The review considers recent experimental studies of biological activity and mechanisms of therapeutic action of rosmarinic acid, luteolin and its sulfated derivatives in diseases associated with disorders of carbohydrate and lipid metabolism. Particular attention is focused on the results of studies showing a high therapeutic potential of these phenolic compounds in their prophylactic and therapeutic use at experimental modeling of type 2 diabetes and hyperlipidemia. Based on the analysis of our results and the literature data putative mechanisms of therapeutic action of rosmarinic acid, luteolin and its sulfated derivatives have been proposed.
Asunto(s)
Cinamatos , Depsidos , Diabetes Mellitus Tipo 2 , Hiperlipidemias , Luteolina , Animales , Cinamatos/farmacocinética , Cinamatos/uso terapéutico , Depsidos/farmacocinética , Depsidos/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animales de Enfermedad , Humanos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Luteolina/metabolismo , Luteolina/farmacocinética , Luteolina/uso terapéutico , Ácido RosmarínicoRESUMEN
A comparative study of antioxidant (radical-interceptor) properties of tryptanthrin (quinazoline alkaloid shows a high anti-inflammatory activity and it is found in many types of different families of higher plants and microorganisms, including the human microbiome) in the systems of 2,2'-azo-bis(2-methylpropionamidin)dihydrochloride-luminol and hemoglobin-hydrogen peroxide-luminol has been conducted and the influence on the permeability of planar bilayer lipid membranes is evaluated. Trolox was used as a reference antioxidant, and ascorbic acid and dihydroquercetin were taken as standards. Tryptanthrin exhibits very weak antioxidant activity, being markedly inferior to the reference standard and antioxidants while testing antioxidant activity in both studied systems. By the efficacy of antioxidative action the substrates in the systems studied can be arranged in the following order: dihydroquercetin > trolox > ascorbic acid > tryptanthrin. Antioxidant potential of tryptanthrin is approximately 1000 and 3000 times lower than that of trolox and bioflavonoid dihydroquercetine, respectively. Tryptanthrin causes no significant changes in the permeability of planar bilayer membranes in a dose range of 0.5 to. 10 µg/ml. Our data show that tryptanthrin displays no significant radical-interceptor and membranotropic activities. It can be assumed that the observed high anti-inflammatory activity of tryptanthrin is not related to the neutralizing effect against reactive oxygen species and the influence on the permeability of cell membranes. The anticipated mechanisms of biological activity of tryptanthrin are discussed.