Physiological studies confirm improvement of memory by Olibanum, a resin from Boswellia species, while little is known about the molecular mechanism by which it affects memory performance. Two master transcription factors, CREB-1 and CREB-2, regulate downstream memory-related genes expression, leading to the long-term memory potentiation. This study addresses the effects of Beta-boswellic acid (β-BA), the main ingredient of Olibanum, and ethanolic extract of the resin from Boswellia serrata on the expression of CREB-1 and CREB-2 genes in B65 cell line. B65 cells were treated with β-BA or ethanolic extract of Olibanum in different doses and time intervals and the cell viability/toxicity was measured by MTT assay. Total RNA was extracted from the treated and untreated control cells and cDNA was synthesized. The expression levels of CREB-1 and CREB-2 genes were quantified by Real-time PCR. MTT assays revealed 50% inhibitory concentrations of 42. 05, 29. 63, and 21. 78 μ g/mL for ethanolic extract of Olibanum and 89. 54, 44. 05, and 21. 12 μ M for β-BA at 24, 48, and 72 h time intervals respectively. Both β-BA and ethanolic extract of Olibanum altered CREB-1 and CREB-2 gene expression levels in time-dependent but not in dose-dependent way. However, β-BA showed stronger and more stable effects. The expression levels of the both genes followed an alternate upregulation and downregulation pattern, but in opposite directions, in response to the both solutions with the progress of time. These results suggest that Olibanum possibly improves memory performance, at least partially, by regulating the levels of CREB-1 and CREB-2 transcription factors via positive/negative-feedback loops.

Antidepressant activity of crocin, saffron main component, has been established before. Based on previous study, it is suggested that elevation in the levels of BDNF (brain- derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide could be considered as one probable molecular mechanisms involved in antidepressant activity of long term crocin administration in the rat hippocampus. In this study we further investigated whether the antidepressant activity of crocin in long term administration was associated with alteration in these factors in the rat cerebellum.Crocin (12.5, 25 and 50 mg/kg/day) and imipramine (10 mg/kg/day) were administered interaperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were dissected. BDNF, VGF, CREB, and phospho- CREB (P-CREB) protein and mRNA levels in the rat cerebellum were evaluated using Western blot and quantitative reverse transcription- polymerase chain reaction (qRT-PCR).In the current study significant increases in mRNA and protein levels of VGF, CREB and(BDNF) in long term crocin treatment were not observed in the rat cerebellum. Although a slight increase was observed in protein level of P-CREB compared to normal saline, but it was not significant.It is concluded that antidepressant activity of crocin might be partially mediated to CREB. Moreover, other factors rather than BDNF and VGF neuropeptides may alter following long term crocin treatment in the cerebellum. To understand the precise mechanism of crocin antidepressant effects in the cerebellum, longer duration of crocin treatment in further studies is recommended.