Involvement of Nrf2 and NF-kB Pathways in the Antioxidant and Anti-Inflammatory Effects of Metformin in LPS Activated BV-2 Microglial Cells

Abstract ID 98699 Poster Board 129 Chronic neuroinflammation is associated with several neurodegenerative diseases, such as Alzheimer's disease. Microglia are the brain's primary immune cells, and when excessively activated, they cause neuronal damage by releasing pro-inflammatory cytokines and reactive oxygen intermediates. Therefore, suppressing microglia-mediated inflammation and oxidative stress has been considered an important management strategy in neurodegenerative disease therapy. Metformin, mainly used for Type 2 Diabetes therapy, has been shown in in-vitro and in-vivo studies to have anti-inflammatory properties. Thus, we hypothesize that metformin provides neuroprotective properties by suppressing inflammation and oxidative stress by inhibiting the NF- κB1a pathway and activating the Nrf2 pathway. To assess the potential neuroprotective role of metformin as an anti-inflammatory and antioxidant, stimulated BV-2 microglial cells were treated with 1μg/mL LPS for one hr. followed by 24 hr. incubation in the presence and absence of 1mM, 2mM, and 4mM metformin. This study used Alamar Blue (Resazurin) assay, PrimePCR array, and Western blotting technology to evaluate cell viability and inflammatory and oxidative stress signaling pathways. Our findings indicate that metformin significantly downregulated the expression of mRNA of NF- κB1a, IL-1b, and CCl2(MCP-1), demonstrating that metformin can reduce inflammation. Metformin also considerably increased the expression of mRNA of Hmox1 and IL-10, suggesting its antioxidant and neuroprotective effects. The Western blot results also revealed that metformin significantly increased the protein expression of Nrf2, which participates in the transcription of many antioxidant genes. According to these results, metformin's anti-inflammatory and antioxidant effects may be mediated by inhibiting the NF- κB1a pathway and activating the Nrf2 signaling pathway. Modulating these pathways by metformin in the brain may protect neuronal cells against neuroinflammation, oxidative stress, and cell death. In conclusion, these findings suggest that metformin is not only beneficial for the treatment of Type 2 Diabetes but may also have therapeutic potential to prevent or slow the progression of neurodegenerative diseases, such as Alzheimer's disease, by reducing oxidative stress and neuroinflammation. This research was funded by a grant from the National Institute on Minority Health and Health Disparities (NIMHD) (U54 MD007582).