Effects of saffron and its constituents, crocin-1, crocin-2, and crocetin on α-synuclein fibrils.

Saffron, the stigma of Crocus sativus Linné (Iridaceae family), has been known to inhibit aggregation of ß-amyloid, a nerve tissue protein. α-Synuclein (αS) is a 140-amino acid protein found abundantly in various regions of the brain. Its abnormal aggregation and accumulation in nerve tissue are said to cause neurodegenerative diseases such as Parkinson's disease, Lewy body dementia, and multiple-system atrophy. This study (part of this study was presented at the 137th Annual Meeting of the Pharmaceutical Society of Japan) examined the effects of saffron, its constituents (crocin-1, crocin-2, crocetin, and safranal), and crocetin structural analogs (hexadecanedioic acid, norbixin, and trans, trans-muconic acid) on αS aggregation, and αS fibril dissociation. Saffron dose-dependently inhibited αS aggregation and dissociated αS fibrils by thioflavin T fluorescence assay. These effects were observed by transmission electron microscopy, which showed reduced and shortened αS fibrils. Crocin-1, crocin-2, and crocetin showed anti-aggregation and fibril dissociation effects, with crocetin being the most potent. The effects of norbixin were weaker than those of crocetin, and the other crocetin structural analogs showed no effects. These results show that saffron and its constituents (crocin-1, crocin-2, and crocetin) can be effective in preventing and treating diseases caused by abnormal αS aggregation.

Agarwood Inhibits Histamine Release from Rat Mast Cells and Reduces Scratching Behavior in Mice: Effect of Agarwood on Histamine Release and Scratching Behavior.

OBJECTIVES: This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. METHODS: Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate the effects of agarwood. The hyaluronidase activity and the 3',5'-cyclic adenosine monophosphate (cAMP) levels in mast cells were examined to investigate the mechanisms for the inhibition of histamine release. The correlation between the inhibitory effects of agarwood on histamine release and the content of its typical ingredients, a 2-(2-phenylethyl)chromone derivatives, was analyzed using thin-layer chromatography. RESULTS: Agarwood showed an inhibitory effect on mast-cell histamine release induced by compound 48/80 or Con A without any effect on hyaluronidase activity; this effect involves an increase in the cAMP levels in mast cells. Oral administration of agarwood showed an inhibitory effect on compound 48/80-induced scratching behavior in mice. The inhibitory effects of agarwood on histamine release were quite different, depending on the area where the agarwood was produced, its quality, and its market price. No correlation was found between the inhibitory effects of agarwood on histamine release and the typical ingredients of agarwood, which are 2-(2-phenylethyl)chromone derivatives. CONCLUSION: These results show that agarwood inhibits histamine release from mast cells partially through an increase in the cAMP levels in cells. We suggest that some active ingredients of agarwood must be effective on oral intake and that agarwood can be used to treat patients with a number of conditions, including urticaria, atopic dermatitis, and bronchial asthma, in which an increase in histamine release occurs. Differences in the pharmacological effects of this crude drug among markets may provide important information for the quality control of this herbal medicine.

Defensive function of persecutory delusion and discrepancy between explicit and implicit self-esteem in schizophrenia: study using the Brief Implicit Association Test.

BACKGROUND: If delusions serve as a defense mechanism in schizophrenia patients with paranoia, then they should show normal or high explicit self-esteem and low implicit self-esteem. However, the results of previous studies are inconsistent. One possible explanation for this inconsistency is that there are two types of paranoia, "bad me" (self-blaming) paranoia and "poor me" (non-self-blaming) paranoia. We thus examined implicit and explicit self-esteem and self-blaming tendency in patients with schizophrenia and schizoaffective disorder. We hypothesized that patients with paranoia would show lower implicit self-esteem and only those with non-self-blaming paranoia would experience a discrepancy between explicit and implicit self-esteem. METHODS: Participants consisted of patients with schizophrenia and schizoaffective disorder recruited from a day hospital (N=71). Participants were assessed for psychotic symptoms, using the Brief Psychiatric Rating Scale (BPRS), and self-blaming tendency, using the brief COPE. We also assessed explicit self-esteem, using the Rosenberg Self-Esteem Scale (RSES), implicit self-esteem, using Brief Implicit Association Test (BIAT), and discrepancy between explicit and implicit self-esteem. RESULTS: Contrary to our hypothesis, implicit self-esteem in paranoia and nonparanoia showed no statistical difference. As expected, only patients with non-self-blaming paranoia experienced a discrepancy between explicit and implicit self-esteem; other groups showed no such discrepancy. CONCLUSION: These results suggest that persecutory delusion plays a defensive role in non-self-blaming paranoia.