Protection of Beta Boswellic Acid against Streptozotocin-induced Alzheimer's Model by Reduction of Tau Phosphorylation Level and Enhancement of Reelin Expression.

Alzheimer's disease is a growing general health concern with huge implications for individuals and society. Beta boswellic acid, a major compound of the Boswellia serrata plant, has long been used for the treatment of various inflammatory diseases. The exact mechanism of beta boswellic acid action in Alzheimer's disease pathogenesis remains unclear. In the current study, the protective effect of beta boswellic acid on streptozotocin-induced sporadic Alzheimer's disease was surveyed. Alzheimer's disease model was induced using streptozotocin followed by an assessment of the treatment effects of beta boswellic acid in the presence of streptozotocin. The prevention effect of beta boswellic acid on Alzheimer's disease induction by streptozotocin was evaluated. Behavioral activities in the treated rats were evaluated. Histological analysis was performed. Phosphorylation of tau protein at residues Ser396 and Ser404 and the expression of reelin protein were determined. Glial fibrillary acidic protein immunofluorescence staining was applied in the hippocampus regions. Our findings indicated that beta boswellic acid decreased traveled distance and escape latency in the prevention (beta boswellic acid + streptozotocin) and treatment (streptozotocin + beta boswellic acid) groups compared to control during the acquisition test. It increased "time spent" (%) in the target quadrant. Reelin level was enhanced in rats treated with beta boswellic acid. Tau hyperphosphorylation (p-tau404) and glial fibrillary acidic protein were decreased in the prevention group while the expression of reelin protein in both groups was increased. We could suggest that the anti-inflammatory property of beta boswellic acid is one of the main factors involving in the improvement of learning and memory in rats. Therefore the antineurodegenerative effect of beta boswellic acid may be due to its ability to reactivate reelin protein.

The Effects of Alpha Boswellic Acid on Reelin Expression and Tau Phosphorylation in Human Astrocytes.

Reelin is an extracellular glycoprotein which contributes to synaptic plasticity and function of memory in the adult brain. It has been indicated that the Reelin signaling cascade participates in Alzheimer's disease (AD). Besides the neurons, glial cells such as astrocytes also express Reelin protein. While functional loss of astrocytes has been reported to be associated with AD, dysfunction of astrocytic Reelin signaling pathway has not received much attention. Therefore, we investigated the effects of α-boswellic acid (ABA) as one of the major component of Boswellia serrata resin on primary fetal human astrocytes under a stress paradigm as a possible model for AD through study on Reelin cascade. For this aim, we used streptozotocin (STZ), in which from an outlook generates Alzheimer's hallmarks in astrocytes, and assayed Reelin expression, Tau and Akt phosphorylation as well as reactive oxygen species (ROS) generation and apoptosis in the presences of ABA. Our results indicated that while STZ (100 µM) down-regulated the expression of Reelin, ABA (25 µM) up-regulated its expression (p < 0.01) for 24 h. ABA efficiently reduced hyperphosphorylated Tau (Ser404) in STZ-treated astrocytes (p < 0.01). Furthermore, STZ-induced apoptosis by increasing cleaved caspase three (p < 0.01) and ROS generation (p < 0.01), a further pathological hallmark of Tauopathy. On the other hand, ABA decreased ROS generation and promoted proliferation of astrocytes through elevating Survivin expression (p < 0.01). These results showed that ABA could be considered as a potent therapeutic agent for prevention and decreasing the progression of Alzheimer's hallmarks in astrocytes; however, more in vivo studies would be needed.