Achyranthes bidentata polypeptide k suppresses neuroinflammation in BV2 microglia through Nrf2-dependent mechanism

Microglia play an important role in immune defense and tissue repair of central nervous system (1). Under normal conditions, microglial cells are in a static state, participating in the maintenance of homeostasis in the brain. Factors such as brain damage, infection or harmful toxins activate microglia, causing neuroinflammation (2). Neuroinflammation can be good or bad for neurons in nearby areas, like a double-edged sword in the brain (3). The functional phenotypes of microglia largely determine the pros and cons of neuroinflammation, mainly the pro-inflammatory M1-type and the anti-inflammatory M2-type (4,5). M1-type microglia mediate inflammation by releasing pro-inflammatory mediators like tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, nitric oxide (NO), and reactive oxygen series (ROS), etc., while M2-type microglia inhibit inflammation mainly by producing anti-inflammatory factors, such as IL-4, IL-10, transformation growth factor β (TGF-β) (6-9). Some studies suggest that the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in the anti-inflammatory effect of the M2-type microglia (10,11). Nrf2 is a key factor of brain endogenous defense system, which can be produced by microglial cells in response to oxidative stress (12,13). Studies showed that activation of Nrf2 and its downstream heme oxygenase-1 (HO-1) could suppress lipopolysaccharide (LPS)-induced neuroinflammation both in vivo and in vitro (14-16). A large body of evidence demonstrate that nuclear factor kappa B (NF-κB) also plays a key role in the process of releasing inflammatory mediators in the activated M1-type microglia, which is thought to be the main regulator of the M1 phenotype (17-20). From this perspective, to regulate the function of microglial cells by targeting Nrf2 and/or NF-κB with active compounds may help to prevent inflammation-mediated neurotoxicity