RESUMEN
Osteoclasts are multinucleated cells that originate from hemopoietic stem cells. Targeting over activated osteoclasts is thought to be an effective therapeutic approach to osteoporosis. In a previous study, we reported that Tatarinan O, a lignin-like compound, suppressed RANKL-induced osteoclastogenesis. In this study, we further examined the effects on osteoclast formation of three lignin-like compounds including Tatarinan N (TN), Tatarinan U (TU) and Tatarinan V (TV), all containing a common structure of asarone. We found that only TN suppressed RANKL-induced osteoclast differentiation, bone resorption pit formation and F-acting ring formation. TU and TV did not influence RANKL-induced osteoclastogenesis. We also found that TN dose-dependently inhibited the expression of osteoclastogenesis-associated genes, including TRAP, cathepsin K and MMP-9. Furthermore, we found that TN down-regulated the key transcription factor NFATc1 and c-Fos by preventing the activation of NF-κB and phosphorylation of MAPKs including ERK1/2 and p38 but not JNK. TN attenuated calcineurin expression via suppression of the Btk-PLCγ2 cascade and reduction of intracellular Ca2+, modulating NFATc1 activation. Taking together, our results indicated that TN might have therapeutic potential for osteoporosis.
Asunto(s)
Anisoles/farmacología , Células de la Médula Ósea/fisiología , Lignina/farmacología , Osteoclastos/fisiología , Osteoporosis/tratamiento farmacológico , Derivados de Alilbenceno , Animales , Anisoles/química , Anisoles/uso terapéutico , Calcineurina/metabolismo , Señalización del Calcio , Técnicas de Cultivo de Célula , Diferenciación Celular , Lignina/química , Lignina/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , OsteogénesisRESUMEN
The commercially available alpha-asarone injections (CA-ARE) were frequently found to cause severe anaphylactic reactions by the solubilizer contained in the formulation such as polysorbate 80 and propylene glycol. This study aimed to develop a new ARE injection using Kolliphor HS 15 as solubilizing agent (HS 15-ARE) by the dissolution method to resolve its poor solubility problem and reduce the anaphylaxis of CA-AREs caused by Polysorbate 80. The HS 15-ARE micelle showed a homogeneous round shape with the mean particle size of around 13.73 ± 0.02 nm, polydisperse index (PDI) of 0.19 ± 0.01 and solubilizing efficiency of 95.7% ± 2.4%. In vitro and in vivo studies showed that HS 15-ARE is a stable injection presenting the same pharmacokinetic profile with CA-ARE. Moreover, improved therapeutic effect was observed for HS 15-ARE in treating asthma compared to CA-ARE (p < 0.05) with no anaphylactic reactions observed. These results demonstrate that the new formulation of ARE (HS 15-ARE) has a great potential for replacing CA-AREs injections.
Asunto(s)
Anafilaxia/inducido químicamente , Anisoles/administración & dosificación , Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Polietilenglicoles/química , Solventes/química , Estearatos/química , Derivados de Alilbenceno , Anafilaxia/sangre , Animales , Anisoles/efectos adversos , Anisoles/sangre , Anisoles/uso terapéutico , Antiasmáticos/efectos adversos , Antiasmáticos/sangre , Antiasmáticos/uso terapéutico , Asma/sangre , Disponibilidad Biológica , Células Cultivadas , Química Farmacéutica , Modelos Animales de Enfermedad , Estabilidad de Medicamentos , Eritrocitos/efectos de los fármacos , Cobayas , Hemólisis/efectos de los fármacos , Histamina/sangre , Inyecciones Intravenosas , Masculino , Estructura Molecular , Tamaño de la Partícula , Ratas Wistar , Ovinos , Propiedades de Superficie , Distribución TisularAsunto(s)
Anisoles/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Plantas Medicinales , Administración Oral , Derivados de Alilbenceno , Animales , Anisoles/administración & dosificación , Anisoles/farmacología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Modelos Animales de Enfermedad , Hipercolesterolemia/inducido químicamente , Masculino , Ratones , Polisorbatos/química , Triglicéridos/sangreAsunto(s)
Benzoatos/uso terapéutico , Ácido Deshidrocólico/uso terapéutico , Dispepsia/tratamiento farmacológico , Pancreatina/uso terapéutico , Adolescente , Adulto , Anciano , Amidas/uso terapéutico , Anisoles/uso terapéutico , Bromelaínas/uso terapéutico , Niño , Combinación de Medicamentos , Etilaminas/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Elastómeros de Silicona/uso terapéuticoAsunto(s)
Benzoatos/uso terapéutico , Bromelaínas/uso terapéutico , Ácido Deshidrocólico/uso terapéutico , Dispepsia/tratamiento farmacológico , Pancreatina/uso terapéutico , Amidas/uso terapéutico , Anisoles/uso terapéutico , Ensayos Clínicos como Asunto , Combinación de Medicamentos , Etilaminas/uso terapéutico , Estudios de Evaluación como Asunto , Humanos , Elastómeros de Silicona/uso terapéuticoAsunto(s)
Antidepresivos/efectos adversos , Antiparkinsonianos/efectos adversos , Tranquilizantes/efectos adversos , Xerostomía/inducido químicamente , Anisoles/uso terapéutico , Ergotamina/uso terapéutico , Compuestos Heterocíclicos/uso terapéutico , Salivación/efectos de los fármacos , Fumar , Sulfuros/uso terapéutico , Xerostomía/diagnóstico , Xerostomía/tratamiento farmacológicoRESUMEN
Sialor, a sialogogue, was studied in a double-blind crossover trial in patients with autoimmune exocrinopathy (Sjögren's syndrome). Sialor appears to frequently alleviate the symptoms of xerostomia and increase salivary flow rate, and it is rarely associated with side effects. Sialor is useful in management of xerostomia in patients with Sjögren's syndrome and may also be of value in the treatment of xerophthalmia.