Effects of α-lipoic acid on LPS-induced neuroinflammation and NLRP3 inflammasome activation through the regulation of BV-2 microglial cells activation

Microglial cells are known as the main immune cells in the central nervous system, both regulating its immune response and maintaining its homeostasis. Furthermore, the antioxidant alpha-lipoic acid (LA) is a recognized therapeutic drug for diabetes because it can easily invade the blood-brain barrier. This study investigated the effect of alpha-LA on the inflammatory response in lipopolysaccharide (LPS)-treated BV-2 microglial cells. Our results revealed that alpha-LA significantly attenuated several inflammatory responses in BV-2 microglial cells, including pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin (IL)-6, and other cytotoxic molecules, such as nitric oxide and reactive oxygen species. In addition, alpha-LA inhibited the LPS-induced phosphorylation of ERK and p38 and its pharmacological properties were facilitated via the inhibition of the nuclear factor kappa B signaling pathway. Moreover, alpha-LA suppressed the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, multiprotein complexes consisting of NLRP3 and caspase-1, which are involved in the innate immune response. Finally, alpha-LA decreased the genes accountable for the M1 phenotype, IL-1 beta and ICAM1, whereas it increased the genes responsible for the M2 phenotype, MRC1 and ARG1. These findings suggest that alpha-LA alleviates the neuroinflammatory response by regulating microglial polarization.