Presenting Author Florida A&M University Tallahasse, Florida
Neurodegeneration is characterized by slow and progressive loss of neuronal cells and synapses in different brain regions. These pathologic effects are the major feature of Alzheimers disease (AD), leading to a decline in learning and memory function. The main hallmarks of AD are the aggregation and deposition of amyloid-β peptides on the extracellular surface of neuronal cells. Hyperphosphorylation of tau protein and the formation of neurofibrillary tangles is another feature of AD. Neuroinflammation and oxidative stress follow the accumulation of amyloid-β and neurofibrillary tangles. Continuous activation of microglia cells, known as the resident, innate immune cells in the brain, participates in producing numerous neurotoxic factors, including nitric oxide and reactive oxygen species (ROS), which induce neurodegeneration. Numerous natural compounds, such as cardamonin, a bioactive compound found in many plants, have been reported to exert multiple therapeutic properties, including anti-cancer, anti-inflammatory, antioxidant, antiviral antibiotic, antifungal, and antiallergic activities. This study examined the effects of cardamonin on LPS-activated BV-2 microglial cells. Results of this study showed that cardamonin concentrations of 6.25 to 50 µM reduced over 95% the release of NO in LPS-activated BV-2 cells, compared to the cells treated with LPS only (Plt;0.001). Moreover, cardamonin significantly decreased the cellular production of SOD 3-fold (P lt; 0.05) and increased the levels of expression of CAT 2.5-fold (P lt; 0.05) and glutathione 2-fold (p lt; 0.05) in the LPS-activated BV-2 cells. In RT-PCR assays, cardamonin increased the mRNA expression of CAT and decreased the levels of NOS2, the enzyme responsible for the production of NO and associated with inflammatory processes. Furthermore, cardamonin downregulated the mRNA expression of CCL5/RANTES (5-fold), which promotes the recruitment and activation of inflammatory cells. Also, cardamonin downregulated SLC38A1 (3-fold), whose expression is upregulated during oxidative stress, and TXNIP (2-fold) that regulates thioredoxin, an important redox protein that controls levels of ROS in cells. The data show cardamonin efficacy in modulating proteins and genes involved in inflammation and the control of elevated intracellular levels of ROS. In conclusion, these findings suggest that cardamonin may have potential in the therapy of microglia-derived neurodegeneration, helping to prevent or slow the progression of the disease in the CNS.
This research was supported by NIH Grants U54 MD007582 and P20 MD 006738.
