فهرست مطالب آسیه جبلی

The therapeutic properties of Olibanum have been considered in traditional medicine since ages past. Recent studies indicated the effect of Olibanum on memory enhancement and prevention/treatment of Alzheimer's disease. Fragile X mental retardation protein is the product of the FMR1 gene that mediates memory formation through the development of communications between nerve cells. MAP1B is the FMRP target mRNA and its translation is inhibited by the effect of FMRP. Disturbance in the expression of FMR1 causes fragile X syndrome. Therefore, the aim of this study was to investigate the effect of aqueous extract of Olibanum on the expression of FMR1 and MAP1B genes in hippocampal tissue samples of rats. This study was conducted on 18 rats which were divided into groups of control (n=6) and two treatment groups with 75 (n=6) and 150 mg/kg (n=6) concentrations of aqueous extract of Olibanum. The hippocampus of rats was isolated after eight weeks of treatment by Olibanum extract.  Total RNA was extracted and cDNA was synthesized in this study. Subsequently, the expression of FMR1 and MAP1B genes was evaluated by a real-time polymerase chain reaction. Ethics code:IR.TBZMED.REC.1396.1000 According to the results, the aqueous extract of Olibanum at a concentration of 75 mg/kg increased the expression of FMR1. In addition, MAP1B gene expression decreased in a dose-dependent manner following treatment with Olibanum extract. However, these changes are not statistically significant (P>0.05). The FMRP is a negative translation regulator that mediates synaptic neuronal transmission through inhibition translation of target mRNA, such as MAP1B. Olibanum probably leads to synaptic flexibility and memory improvement through increasing the expression of FMR1 in neuronal cells. This study could pave the way on the use of Olibanum in the treatment of patients with fragile X syndrome in the future.

Pancreatic cancer is ranked as the fourth leading cause of cancer related death. The survival rate of patients is very low and the mortality rate in men is higher than that of women. Various hereditary and non- hereditary factors are involved in the formation of pancreatic cancer; one of the important non- hereditary factors is smoking. Besides, it is known that the risk of pancreatic cancer in patients with diabetes mellitus is twice as high as in the non-diabetic population. Hereditary conditions also include genetic (activation of oncogenes and inactivation of tumor suppressor genes) and epigenetic changes (lncRNA). The mutation in KRAS oncogene is observed in 95% of the patients with pancreatic cancer. Despite the common use of ultrasound and tumor markers in diagnosing pancreatic cancer, their importance as powerful diagnostic tools has been challenged. An innovation in common therapeutic strategies such as chemotherapy, immunotherapy, and gene therapy based on genetic vectors has provided a promising tool for treatment.  Using oncolytic viruses with selective proliferation in cancer cells and minimal adverse effects has opened a new perspective on the future of treatment of this cancer. In addition, novel technologies in gene editing including CRISPR have allowed the genome manipulation of cancer cells to identify and regulate the molecular pathways involved in pancreatic cancer. Considering that multiple genetic and epigenetic changes play a role in the pathogenesis of this cancer, simultaneous control of these pathways with multiple therapies can be a useful therapeutic strategy for pancreatic cancer.

In the past, olibanum was used as an incense and perfume and a remedy for treating various diseases. Now, it is confirmed that olibanum improves memory and has a role in treatment and prevention of Alzheimer disease. CaMKIIα gene is known as molecular memory because of its role in cellular processes associated with memory. The aim of this research was to study the effect of ethanolic extract of olibanum on the expression of CaMKIIα in B65 and PC12 cells. To determine the effect of olibanum on cell viability, MTT assay was done and cells were treated with the extract in different concentrations and times. To study the gene expression, the cells were treated by two concentrations of the extract at four time points. Then, RNA was extracted, cDNA was synthesized, and the expression of CaMKIIα was quantified by qPCR. The qPCR data revealed that olibanum alternately changed the expression of CaMKIIα in a reducing and increasing pattern over time in B65 cells. However, the extract could not induce the expression of this gene in PC12 cells. According to the role of CaMKIIα as molecular memory and the positive effect of olibanum in memory improvement, current results could be helpful in understanding the molecular mechanisms by which olibanum affects memory performance.

Long-term memory depends on protein synthesis. The product of Camkiv gene promotes memory via activating its proteins. The treatment of laboratory animals by Olibanum leads to memory improvement and the recovery of Alzheimer. Therefore, the aim of this study is the evaluation of Olibanum ethanolic extract on the Camkiv expression in PC12 cells. Olibanum toxicity on the cell viability was investigated by MTT test. Cells were treated with concentrations 10,25,40,55,70 and 85 μg/ml of extract in time intervals 12,24,48 and 72 hours and their absorption rate was measured. Then, cells were treated by concentrations 2 and 20 μg/ml of extract in mentioned times. Extracted RNA was converted into cDNA and real-time PCR performed. Cell death was raised by increasing time and concentration of extract treatment. IC50 values were obtained as 71.01, 52.95, 21.05 and 13.85 μg/ml in 12, 24, 48 and 72 hours of treatment, respectively. Besides, concentrations 2 and 20 μg/ml significantly increased Camkiv expression following 24 hour treatment. The maximum expression of Camkiv was observed in 48 hour treatment. The effect of Olibanum on gene upregulation was stable until 72 hours. The Olibanum ethanolic extract can remarkably upregulate Camkiv expression for a long time. These results are consistent with the previous studies indicating the effect of Olibanum on upregulation of Bdnf, Camkiv -downstream gene. However, regarding the existence of the two-direction pathway in the expression regulation of Bdnf and Camkiv , comprehensive studies are required to determine exact mechanism of Olibanum function in the brain.

The most important effects of Frankincense on memory are included prevention and relative treatment of Alzheimer disease, as well as memory enhancement of off springs of the rats that had received Frankincense during their pregnancy and lactation period. Considerably, Camk4, one of the important memory genes, induces downstream memory genes expression through phosphorylation and activation of transcription factors. Here, we aimed to study the effects of aqueous extract of Frankincense on the Camk4 gene expression in PC12 and B65 cell lines.
The effect of extract on the cell viability was evaluated by cell treatment in two time intervals with six concentrations of extract and 50% inhibition concentration was obtained. In this way, for gene expression studies, cells were treated by two concentrations of extract in two time points. RNA was extracted and converted to cDNA and qPCR was performed to investigate the expression of Camk4 gene.
The aqueous extract of Frankincense decreased the cell viability in a time and concentration dependent pattern. However, the extract was more toxic for B65 cell line than PC12. Also, it significantly increased the expression of Camk4 gene in the cells. Nevertheless, the increase was dependent to the extract concentration and the cell type. The low concentration of the extract was more effective to the expression of Camk4 gene than the high concentration as well as to its expression in the PC12 cell line than B65.
This study showed that Frankincense could regulate the expression of Camk4 gene in a concentration dependent pattern. However, further studies are needed to identify the mechanisms of Frankincense action in different cells.