Cerebralcare Granule® attenuates cognitive impairment in rats continuously overexpressing microRNA-30e.

Previous studies have demonstrated that dysregulation of micro (mi)RNAs is associated with the etiology of various neuropsychiatric disorders, including depression and schizophrenia. Cerebralcare Granule® (CG) is a Chinese herbal medicine, which has been reported to have an ameliorative effect on brain injury by attenuating blood­brain barrier disruption and improving hippocampal neural function. The present study aimed to evaluate the cognitive behavior of rats continuously overexpressing miRNA­30e (lenti­miRNA­30e), prior to and following the administration of CG. In addition, the mechanisms underlying the ameliorative effects of CG were investigated. The cognitive ability of the rats was assessed using an open­field test and a Morris water maze spatial reference/working memory test. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect neuronal apoptosis in the dentate gyrus of the hippocampus. Immunohistochemical analysis and western blotting were conducted to detect the expression levels of B­cell lymphoma 2 (BCL­2) and ubiquitin­conjugating enzyme 9 (UBC9), in order to examine neuronal apoptosis. The lenti­miRNA­30e rats exhibited increased signs of anxiety, depression, hyperactivity and schizophrenia, which resulted in a severe impairment in cognitive ability. Furthermore, in the dentate gyrus of these rats, the expression levels of BCL­2 and UBC9 were reduced and apoptosis was increased. The administration of CG alleviated cognitive impairment, enhanced the expression levels of BCL­2 and UBC9, and reduced apoptosis in the dentate gyrus in the lenti­miRNA­30e rats. No significant differences were detected in behavioral indicators between the lenti­miRNA­30e rats treated with CG and the normal controls. These findings suggested that CG exerts a potent therapeutic effect, conferred by its ability to enhance the expression levels of BCL­2 and UBC9, which inhibits the apoptotic process in neuronal cells. Therefore, CG may be considered a potential therapeutic strategy for the treatment of cognitive impairment in mental disorders.

Effects of coffee and caffeine on bladder dysfunction in streptozotocin-induced diabetic rats.

AIM: To explore the effects and mechanisms of caffeine and coffee on bladder dysfunction in streptozotocin-induced diabetic rats. METHODS: Sprague-Dawley male rats were divided randomly into 4 groups: control, diabetes mellitus (DM), DM with coffee treatment, and DM with caffeine treatment. The diabetic rat was induced by intraperitoneal injection of streptozotocin (60 mg/kg). After 7 weeks of treatment with coffee and caffeine, cystometrogram, contractile responses to electrical field stimulation (EFS) and acetylcholine (ACh), and cyclic AMP (cAMP) concentration of the bladder body and base were measured. RESULTS: The bladder weight, volume threshold for micturition and post-void residual volume (PVR) in the diabetic rats were significantly higher compared to those in the control animals. Coffee or caffeine treatment significantly reduced the bladder weight, bladder capacity and PVR in the diabetic rats. DM caused significant decreases in cAMP concentration of the bladder and coffee and caffeine caused upregulation of cAMP content in the diabetic bladder. In addition, coffee and caffeine tended to normalize the altered detrusor contractile responses to EFS and ACh in the diabetic rats. CONCLUSION: These results indicate that caffeine and coffee may have beneficial effects on bladder dysfunction in the early stage of diabetes by increasing cAMP content in the lower urinary tract, recovering the micturition reflex and improving the detrusor contractility.