RESUMO
Schizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal), and cognitive impairment. In the present study, we explored whether D-pinitol could ameliorate schizophrenia-like behaviors induced by MK-801, an N-methyl-D-aspartate receptor antagonist. Acoustic startle response test was conducted to evaluate the effects of D-pinitol on sensorimotor gating function. Social interaction and novel object recognition tests were employed to measure the impact of D-pinitol on social behavior and cognitive function, respectively. Additionally, we examined whether D-pinitol affects motor coordination. Western blotting was conducted to investigate the mechanism of action of D-pinitol. Single administration of D-pinitol at 30, 100, or 300 mg/kg improved the sensorimotor gating deficit induced by MK801 in the acoustic startle response test. D-Pinitol also reversed social behavior deficits and cognitive impairments induced by MK-801 without causing any motor coordination deficits. Furthermore, D-pinitol reversed increased expression levels of pNF-kB induced by MK-801 treatment and consequently increased expression levels of TNF-α and IL-6 in the prefrontal cortex. These results suggest that D-pinitol could be a potential candidate for treating sensorimotor gating deficits and cognitive impairment observed in schizophrenia by down-regulating transcription factor NF-κB and pro-inflammatory cytokines in the prefrontal cortex.
Assuntos
Disfunção Cognitiva , Esquizofrenia , Camundongos , Animais , Maleato de Dizocilpina/efeitos adversos , Reflexo de Sobressalto/fisiologia , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. (Asteraceae) has been used as an antipyretic and anti-parasitic drug in traditional medicine for more than 2000 years. It has also been prescribed to treat symptoms caused by deficiency of Yin, which might be observed in menopausal state from the point of view of traditional medicine. AIM OF THE STUDY: We hypothesized that A. annua might be useful for treating menopausal disorders with less adverse effects than hormone replacement therapy. Thus, the aim of the present study was to investigate effects of A. annua on postmenopausal symptoms of ovariectomized (OVX) mice. MATERIALS AND METHODS: OVX mice were employed as a model for postmenopausal disorders. Mice were treated with a water extract of A. annua (EAA; 30, 100 or 300 mg/kg, p.o.) or 17ß-estradiol (E2; 0.5 mg/kg, s.c.) for 8 weeks. Open field test (OFT), novel object recognition task (NOR), Y-maze test, elevated plus maze test (EPM), splash test and tail suspension test (TST) were conducted to determine whether EAA could ameliorate postmenopausal symptoms. Phosphorylated levels of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and glycogen synthase kinase-3ß (GSK-3ß), ß-catenin and expression level of synaptophysin in the cortex and hippocampus were evaluated by Western blot analysis. RESULTS: EAA treatment significantly increased the discrimination index in NOR, decreased the time in closed arm than in open arm in EPM, increased grooming time in splash test, and decreased immobility time in TST, as did E2 treatment. In addition, decreased phosphorylation levels of ERK, Akt, GSK-3ß, and ß-catenin and expression levels of synaptophysin in the cortex and hippocampus after OVX were reversed by administration of EAA and E2. CONCLUSION: These results suggest that A. annua can ameliorate postmenopausal symptoms such as cognitive dysfunction, anxiety, anhedonia, and depression by activating ERK, Akt, and GSK-3ß/ß-catenin signaling pathway and hippocampal synaptic plasticity, and that A. annua would be a novel treatment for postmenopausal symptoms.
Assuntos
Artemisia annua , Proteínas Proto-Oncogênicas c-akt , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Glicogênio Sintase Quinase 3 beta , beta Catenina/metabolismo , Sinaptofisina , Pós-Menopausa , MAP Quinases Reguladas por Sinal Extracelular/metabolismoRESUMO
BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSION: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.