ABSTRACT
Physalin B (PB), one of the major active steroidal constituents of Solanaceae Physalis plants, has a wide variety of biological activities. We found that PB significantly down-regulated β-amyloid (Aβ) secretion in N2a/APPsw cells. However, the underlying mechanisms are not well understood. In the current study, we investigated the changes in key enzymes involved in β-amyloid precursor protein (APP) metabolism and other APP metabolites by treating N2a/APPsw cells with PB at different concentrations. The results indicated that PB reduced Aβ secretion, which was caused by down-regulation of β-secretase (BACE1) expression, as indicated at both the protein and mRNA levels. Further research revealed that PB regulated BACE1 expression by inducing the activation of forkhead box O1 (FoxO1) and inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). In addition, the effect of PB on BACE1 expression and Aβ secretion was reversed by treatment with FoxO1 siRNA and STAT3 antagonist S3I-201. In conclusion, these data demonstrated that PB can effectively down-regulate the expression of BACE1 to reduce Aβsecretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.
Subject(s)
Humans , Alzheimer Disease , Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Peptides/metabolism , Aspartic Acid Endopeptidases/metabolism , Down-Regulation , Forkhead Box Protein O1/genetics , Phosphorylation , STAT3 Transcription Factor/metabolism , SecosteroidsABSTRACT
En el campo de la Clínica Médica, la vitamina D se asocia tradicionalmente con la regulación del metabolismo fosfocálcico. Sin embargo, no es el rol exclusivo de esta vitamina dado que tiene diferentes funciones, no menos relevantes. Interviene en procesos tales como la regulación de la tensión arterial con la ulterior disminución del riesgo de enfermedad cardiovascular, el aumento del tono y fuerza muscular y consecuentemente en la prevención de las caídas en adultos mayores y su derivación más grave, las fracturas y la participación en procesos inmunitarios con disminución del riesgo de padecer alergias, cáncer, diabetes e incluso esclerosis múltiple. Dada la importancia de la Vitamina D en patologías con alta prevalencia en la tercera edad, esimportante analizar sus niveles en este grupo poblacional y proceder a su suplementación cuando así se requiera.
Vitamin D is associated in the field of Medical Clinic, traditionally shaped bounded to the regulation of phospho-calcium metabolism; however, this is not an exclusive role: Vitamin D has several different functions longer involved in processes such as the regulation of blood pressure with subsequent decreased risk of cardiovascular disease; increased muscle tone and strength and consequently in the prevention of falls in older adults and its most severe consequence, the fractures; involvement in immune processes with reduced risk of allergies, cancer, diabetes and even multiple sclerosis. Given the importance of the Vitamin.D inpathology with high prevalence in the elderly, it seems important to analyze the level of this element in that population group and proceed to supplementation when required.
Subject(s)
Humans , Aged , Aged, 80 and over , Vitamin D , Health of the Elderly , Secosteroids , AvitaminosisABSTRACT
Physalis angulata is a specie of the Solanaceae family, which edible fruit is used in several countries of tropical and subtropical regions of the world as medicinal and fruit-tree. This review shows research over the last 30 years, about traditional uses, chemical constituents and pharmacology of this specie. The studies related to traditional uses show that P. angulata is known for its antimalarial, anti-inflammatory and post-partum treating properties. It presents the different pharmacological experiments in vitro and in vivo models that have been made, also the identification of phytochemical constituents with medicinal importance, the main being physalins and withanolides. Pharmacological studies have shown antiparasitic, anti-inflammatory, antimicrobial, antinociceptive, antimalarial, antileishmanial, immunosuppressive, antiasthmatic diuretic, and antitumor activities, thus validating its traditional uses and demonstrating the great potential of this specie for further development within the pharmaceutical industry.
Physalis angulata, es una especie de la familia Solanaceae, de frutos comestibles, que en diferentes países de regiones tropicales y subtropicales del mundo utilizan como medicinal y frutal. La presente revisión muestra las investigaciones realizadas durante los últimos 30 años, sobre los usos tradicionales, componentes químicos y farmacología de esta especie. Los estudios referidos a los usos tradicionales, muestran que la especie es conocida por propiedades antimaláricas, antiinflamatorias y en el tratamiento de postparto. Se muestran los diferentes experimentos farmacológicos de ensayos in vitro y modelos in vivo que se han realizado, asimismo la identificación de sus constituyentes fitoquímicos con importancia medicinal, siendo los principales las fisalinas y los witanólidos. Los estudios farmacológicos revelan que tiene actividad antiparasitaria, antiinflamatoria, antimicrobiana, antinociceptiva, antimalárica, antileishmania, inmunosupresor, antiasmático, diurético y antitumoral, validando de esta manera sus usos tradicionales y demostrando el gran potencial que tiene esta especie para un mayor desarrollo dentro de la industria farmacéutica.
Subject(s)
Plant Extracts/pharmacology , Plant Extracts/chemistry , Physalis/chemistry , Medicine, Traditional , Secosteroids , Solanaceae/chemistry , WithanolidesABSTRACT
Parameters for microbial transformation of 13-ethyl-3-methoxy-8, 14-seco-gona-1,3,5 (10), 9(11)-tetraene-14,17-dione to its 17 beta-hydroxy derivative by P. farinosa have been standardised in pilot plant fermentors. The yield of the pure crystalline compound was 80%.