ABSTRACT
Introducción: Los ecdiesteroides presentan cualidades únicas dentro del reino vegetal y animal. Su similitud a esteroides endógenos de mamíferos les otorga actividad biológica sobre el tejido muscular esquelético. Sin embargo, su mecanismo de acción está por definirse en su totalidad. Método: Se realizó una revisión narrativa utilizando la evidencia científica más relevante. Se consultaron de las bases de datos Medline, Google Scholar, Scielo y Wiley, incluyéndose y excluyéndose trabajos acordes a los criterios del autor. Resultados: La actividad de los ecdiesteroides, principalmente de la Ecdisterona (Ec), podría deberse a la interacción con Mas, receptor acoplado a proteína-G transmembrana (GPCR), y la posterior activación del receptor de estrógenos β (ER β) no nuclear. Dicho mecanismo de acción induce la activación de la ruta alternativa del Sistema Renina-Angiotensina-Aldosterona (RAA) aboliendo los mecanismos de degradación muscular y, mediante la activación indirecta de Erβ, se suprime la expresión del gen de la miostatina. Esta actividad biológica pudiera conferir a los ecdiesteroides propiedades farmacológicas óptimas para impedir la degradación proteico-muscular, tales como la regeneración y reparación del tejido. Conclusiones: Ec ha demostrado poseer propiedades farmacológicas interesantes para el abordaje alternativo de patologías musculodegenerativas por sus efectos anticatabólicos. Aunque prosigue la investigación para su implementación en la clínica, esta siendo utilizada en la industria deportiva y en ensayos para el tratamiento de diferentes patologías. (AU)
Introduction: Ecdysteroids present unique qualities within the plant and animal kingdoms. Their similarity to en-dogenous mammalian steroids allows them to present biological activity on skeletal muscle tissue. However, this molecules action mechanism remains to be fully understood. Method: A narrative review was carried out using the most relevant scientific evidence. Different databases such as Medline, Google Scholar, Scielo and Wiley were consulted. Works were included or excluded according to the author ́s criterium. Results: Ecdysteroids activity, mostly that of ecdysterone, might be due to the interaction with Mas receptor, a transmembrane G-Protein Coupled Receptor (GPCR), and the subsequent indirect activation of β-Estrogen Recep-tor ́s (β-ER) non-nuclear form. Said action mechanism induces the alternative pathway activation of the Renin-An-giotensin-Aldosterone System (RAAS), abolishing muscular degradation mechanism. Finally, through β-ER activa-tion, the myostatin gene is supressed. This biological activity could provide ecdysteroids optimal pharmacological properties to prevent muscular protein degradation. These include tissue regeneration and repair. Conclusions: Due to its anticatabolic effects, Ec has shown great pharmacological properties that could make it work as an alternative treatment for degenerative muscle pathologies. Although investigations regarding Ec are still in progress, it has already been used by the sports industry and in several clinical trials that focus on the treatment of other diseases. (AU)
Subject(s)
Humans , Muscle, Skeletal , Ecdysterone/pharmacology , Ecdysterone/adverse effects , Receptors, Estrogen , Hypertrophy , Gonadal Steroid Hormones/pharmacologyABSTRACT
Neste trabalho foi avaliado, em roedores, o efeito depressor das frações clorofórmio (CHCl3), acetato de etila (EtOAc) e n-butanol, obtidas das partes subterrâneas de Pfaffia glomerata, empregando-se o teste de tempo de sono barbitúrico como referência. Somente a fração lipofílica (CHCl3:EtOAc, 1:1, m/m) (i.p. 500 mg/kg; v.o. 1000 mg/kg) potenciou o tempo de sono induzido por pentobarbital. A ecdisterona foi isolada e identificada como constituinte majoritário (1,4 por cento m/m) desta fração, através de cromatografia líquida de alta eficiência e métodos espectroscópicos, respectivamente. Este composto potenciou o tempo de sono barbitúrico (100 mg/kg, i.p.; 400 mg/kg, v.o), sem causar hipotermia. Nestas mesmas doses, a ecdisterona não alterou a performance dos animais no rota-rod, esquiva inibitória e labirinto em cruz-elevado, além de não alterar o padrão de convulsões induzidas por pentilenotetrazol. Este perfil indica que esta substância, nestas doses, não apresenta perfil ansiolítico ou neurotóxico. Estes resultados indicam que a ecdisterona é o componente responsável pela ação hipnótica apresentada pela fração lipofílica obtida das partes subterrâneas de P. glomerata.
In this study the depressant effect of fractions from P. glomerata was initially evaluated using the mice barbiturate sleeping time test as reference. The fractions tested were the CHCl3, the EtOAc, the n-BuOH and the aqueous fraction obtained from P. glomerata subterraneous parts. Only the pretreatment with the lipophilic fraction (CHCl3: EtOAc, 1:1, w/w) increased the barbiturate sleeping time (i.p 500 mg/kg; v.o. 1000 mg/kg). Ecdysterone, the main substance isolated from this lipophilic fraction, was identified by spectroscopic methods and its content in the ethanol extract was determined as 1.4 percent (w/w) by HPLC. In order to investigate the hypothesis of ecdysterone displaying a depressant effect on nervous central system, an evaluation toward the hypnotic-sedative and anxiolytic effects of this drug was carried out. Ecdysterone 100 mg/kg, i.p, increased the barbiturate sleeping time without provoking hypothermia; when administered by oral route its minimal effective dose was 400 mg/kg. On the other hand, ecdysterone (100 mg/kg, i.p; 400 mg/kg, p.o) did not impair motor coordination and was ineffective on pentylenetetrazole-induced convulsion, elevated plus-maze and step-down inhibitory avoidance tests, indicating that at these doses the drug does not present an anxiolytic profile and does not cause manifest neurotoxic effects as well. In conclusion, the lipophilic fraction from P. glomerata presents a hypnotic effect being ecdysterone one of the compounds responsible for this CNS activity.
ABSTRACT
As raízes secas da espécie brasileira Pfaffia tuberosa (Spreng.) Hicken foram submetidas a extração com metanol. Deste extrato metanólico foram isolados a ecdisterona e o ácido oleanólico, através de processos de separação por HPLC e cromatografia em coluna. Tanto a ecdisterona como o ácido oleanólico foram identificados comparativamenve com os respectivos padrões. Análise quantitativa por HPLC mostrou 0,23 por cento de ecdisterona. Este teor foi considerado baixo em relação a outra espécie, também brasileira, a Pfaffia iresinoides.
In this paper, we wish to report the isolation and identification of ecdysterone from Pfaffia tuberosa (Spreng.) Hicken. The roots of Pfaffia tuberosa (Spreng.) Hicken were colected in the Mato Grosso State - Brazil. The dried and sliced roots (197g) were extracted with hot MeOH. A suspension of the resulting MeOH extract in the water was treated with n-BuOH. The n-BuOH layer was concentrated in vacuo to give a brown viscous oil (5g), wich was chromatographed on silicagel (65g) using CHCl3 - MeOH - H2O (80:20:10) lower phase, and 15ml fractions were collected. Fractions 11-13 were concentrated and the residual solid was recrystallized from EtOH to afford oleanolic acid (65mg). The crystalline residue obtained from fractions 44-56 was recrystallized from EtOAC-MeOH to give ecdysterone (87mg). Each compound was identified by direct comparison with an authentic sample. Further HPLC quantitative analysis showed lower content of ecdysterone (0,23 percent) compared with that of Pfaffia iresinoides Spreng.
