RESUMEN
Natural moisturizing factor (NMF) in the stratum corneum contributes to the retention of moisture there. The purpose of this study was to determine the penetration of ions in Shotokuseki extract (SE) into the three-dimensional cultured epidermis and the effect of NMF on the biosynthesis of amino acids and pyrrolidone carboxylic acid formation. Various ions, amino acids and pyrrolidone carboxylic acid were quantified by inductively coupled plasma mass spectrometry, fully automatic amino acid analyzer or high-performance liquid chromatography (HPLC) in three-dimensional cultured epidermis after application of SE. Gene expression levels of profilaggrin, calpain1, caspase14, and bleomycin hydrolase, which are involved in NMF production, were determined by reverse-transcription qPCR and bleomycin hydrolase activity was determined by aminopeptidase assay. The application of SE increased Na, K, Mg, Ca, Al, and Fe levels in three-dimensional cultured epidermis. The mRNA levels of the starting material of amino acid synthesis profilaggrin, and calpain1 and bleomycin hydrolase, which are involved in its fragmentation, increased. The activity of bleomycin hydrolase also increased. Furthermore, the levels of amino acids and pyrrolidone carboxylic acid increased in the three-dimensional cultured epidermis. This suggests that the ionic composition of SE may be involved in its moisturizing effect on the stratum corneum.
RESUMEN
The mechanism underlying the improvement in hepatic function by liver hydrolysate (LH) after ethanol-induced hepatic injury is unclear. Therefore, we investigated the effects of LH administration on chronic ethanol-induced hepatic injury in normal rats and the mechanism underlying the improvement of its symptoms by LH. LH attenuated liver damage and reduced oxidative stress after chronic ethanol-induced hepatic injury in normal rats. LH treatment reduced hepatic injury biomarkers of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT). LH treatment also decreased levels of 8-hydroxy-deoxyguanosine (8-OHdG) as oxidative stress marker. LH may prove beneficial to prevent the liver damage of chronic ethanol, at least in part, by alleviating oxidative stress.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Etanol/farmacología , Hígado/metabolismo , Alanina Transaminasa/sangre , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Femenino , Masculino , Malondialdehído/sangre , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa/sangre , Superóxido Dismutasa/metabolismoRESUMEN
We examined whether chondroitin sulfate (CS), a compound used to treat osteoarthritis and joint pain, is effective against partial sciatic nerve ligation (PSNL)-induced neuropathic pain. Repeated oral administration of CS (300 mg/kg, b.i.d. for 20 days) resulted in inhibition of tactile allodynia observed 21 days after PSNL. On day 21, phosphorylation of spinal p38 mitogen-activated protein kinase (MAPK) was attenuated by CS. CS also inhibited c-Fos upregulation in ipsilateral deep dorsal horn (laminae III-IV) neurons, which receive Aß-fiber afferent inputs. These findings suggest that CS attenuates PSNL-induced tactile allodynia by inhibiting spinal p38 MAPK phosphorylation and Aß-fiber activation.
Asunto(s)
Sulfatos de Condroitina/administración & dosificación , Hiperalgesia/tratamiento farmacológico , Ligadura/efectos adversos , Neuralgia/tratamiento farmacológico , Nervio Ciático , Administración Oral , Péptidos beta-Amiloides/metabolismo , Animales , Sulfatos de Condroitina/farmacología , Hiperalgesia/etiología , Masculino , Ratones Endogámicos , Neuralgia/etiología , Fosforilación , Proteínas Proto-Oncogénicas c-fos/metabolismo , Médula Espinal/enzimología , Asta Dorsal de la Médula Espinal/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
We explored the effects of chondroitin sulfate on knee osteoarthritis in a one-year, randomized, double-blind, dose-comparison study. Patients with painful, Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group) or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index and visual analog scale for pain. We made subgroup analyses according to background symptom severity (Lequesne's index ≥8 or <8) in 73 patients. Serum level of cartilage oligomeric matrix protein and hyaluronic acid were also determined. In the subgroup with severe symptoms (Lequesne's index ≥8), the chondroitin sulfate dose of 1560 mg/d improved pain faster after 6 and 9 months' therapy. However, no dose-related effects were found on cartilage oligomeric matrix protein or hyaluronic acid levels. Chondroitin sulfate also had good tolerability. We conclude that chondroitin sulfate is useful for pain control in knee osteoarthritis.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Sulfatos de Condroitina/uso terapéutico , Articulación de la Rodilla/efectos de los fármacos , Osteoartritis de la Rodilla/tratamiento farmacológico , Anciano , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Biomarcadores/sangre , Proteína de la Matriz Oligomérica del Cartílago/sangre , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Ácido Hialurónico/sangre , Japón , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/inmunología , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/fisiopatología , Dimensión del Dolor , Radiografía , Índice de Severidad de la Enfermedad , ComprimidosRESUMEN
We examined the effect of chondroitin sulfate (CS), a compound used in the treatment of osteoarthritis and joint pain, on the formalin-induced tactile allodynia in mice. A repeated oral administration of CS (300 mg/kg, b.i.d.) significantly ameliorated the formalin-induced tactile allodynia from day 10 after formalin injection. On day 14, the phosphorylation of spinal p38 MAPK and subsequent increase in c-Fos-immunoreactive dorsal lumbar neurons were attenuated by the repeated administration of CS. These findings suggest that CS attenuates formalin-induced tactile allodynia through the inhibition of p38 MAPK phosphorylation and subsequent up-regulation of c-Fos expression in the dorsal lumbar spinal cord.
Asunto(s)
Sulfatos de Condroitina/farmacología , Formaldehído , Hiperalgesia/inducido químicamente , Hiperalgesia/prevención & control , Animales , Masculino , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Liver hydrolysate (LH) is used as a pharmaceutical agent in Japan, to enhance liver function. However, the effects of LH on sickness behavior are unknown. This study investigated the effect of LH on sickness behaviors, such as concanavalin A (ConA)-induced reduction of locomotor activity. ConA treatment significantly decreased locomotor activity. The striatal tyrosine hydroxylase (TH) levels were also significantly decreased following ConA treatment. The decreased locomotor activity and TH levels were significantly reversed by LH treatment. LH may prove beneficial for preventing sickness behavior following ConA treatment, at least in part, by activating TH in the striatum.