Available online A B S T R A C TTotal phenolic, flavonoid and anthocyanin contents of dichloromethane, ethyl acetate, ethanol, and aqueous extracts of branches, leaves and fruits from Prunus spinosa were quantified by spectrophotometrical methods and the results showed solvent and botanical organ dependence. In order to detect antioxidant activity, a method based on the reduction of DPPH was carried out. Activity of ethanol, ethyl acetate and aqueous extracts of branches demonstrated a higher scavenging capacity compared to other analysed extracts. Phytochemical analysis allowed detecting flavonoids, coumarins, phenolic acids and flavan-3-ols. Ethanolic extract of branches was subjected to an in vitro digestion. Buccal and gastric digestion had no substantial effect on any of the phenolic compounds. However, these compounds were significantly altered during intestinal digestion. The results showed that a significant proportion of these compounds would be transformed into other unknown and/or undetected structural forms. Furthermore, three phenolic acids, two coumarins, fourteen flavan-3-ols, and six flavonols were identified using HPLC-DAD-ESI-MS.

Objectives Regulation of gene expression is important for the development and function of the nervous system. However, the transcriptional programs altered in psychiatric diseases are not completely characterized. Human gene association studies and analysis of mutant mice suggest that the transcription factor specificity protein 4 (SP4) may be implicated in the pathophysiology of psychiatric diseases. We hypothesized that SP4 levels may be altered in the brain of bipolar disorder (BD) subjects and regulated by neuronal activity and drug treatment. Methods We analyzed messenger RNA (mRNA) and protein levels of SP4 and SP1 in the postmortem prefrontal cortex and cerebellum of BD subjects (n = 10) and controls (n = 10). We also examined regulation of SP4 mRNA and protein levels by neuronal activity and lithium in rat cerebellar granule neurons. Results We report a reduction of SP4 and SP1 proteins, but not mRNA levels, in the cerebellum of BD subjects. SP4 protein and mRNA levels were also reduced in the prefrontal cortex. Moreover, we found in rat cerebellar granule neurons that under non-depolarizing conditions SP4, but not SP1, was polyubiquitinated and degraded by the proteasome while lithium stabilized SP4 protein. Conclusions Our study provides the first evidence of altered SP4 protein in the cerebellum and prefrontal cortex in BD subjects supporting a possible role of transcription factor SP4 in the pathogenesis of the disease. In addition, our finding that SP4 stability is regulated by depolarization and lithium provides a pathway through which neuronal activity and lithium could control gene expression suggesting that normalization of SP4 levels could contribute to treatment of affective disorders.

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