Neuro-inflammation is a defense mechanism to multiple exogenous stimuli and pathogens in the central nervous system (CNS) [1]. It is regarded as the pathogenesis of several neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) [2–4]. Microglia, the main immune defense cells, constitute 10–15% of the glial cell population in the brain [5, 6], which play a vital role in the innate immune response and represent the first line of defense against invading pathogens and pro-inflammatory reactions [7, 8].
In a resting stage, microglia survey the microenvironment in real-time with their ramified processes and secrete various neurotrophic factors to help the development and maintenance of neuronal. When the microglia cells were activated, the shape of them could be changed from highly ramified morphology into ameboid shape. In addition, a series of cellular and molecular events happened. Microglia would secrete a high level of pro-inflammatory factors and cytotoxic mediators, such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) [9]. Therefore, regulation of microglial activation might represent a potential therapeutic strategy for neuro-inflammation.
Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria, which is a strong stimulator of microglial activation [10]. LPS recognizes and binds with LPS-binding protein (LBP) and glycosylphosphatidylinositol-anchored protein CD14, interacts with Toll-like receptor 4 (TLR4) and activates downstream signaling pathway. Activated TLR4 activates the NF-κB signal pathway [11], which is the most frequently used to investigate the mechanism of inflammatory responses in microglia. In response to external stimulation, IκB family members can be phosphorylated and degraded, the NF-κB moved from the cytoplasm into the nucleus, leading to the expression of various pro-inflammatory mediators [12].
Traditionally, Chinese herbal medicine has been widely used to treat various diseases with little side effects, including neurodegenerative diseases [13–17]. Pec is a glycosylated flavone which is first isolated from Linaria vulgaris [18]. Moreover, Pec has widely reported due to its presence in many medicinal plants, such as Cirsium [19]. According to recent studies, Pec has turned out to be good biological activities, including anti-tumor, antioxidant [20], antiviral [21, 22], anti-inflammatory [23, 24] and anti-cancer effects. As for anti-inflammatory effects, a previous study showed that Pec inhibited the acid-induced writhing in mice in a dose-dependent manner [25]. However, the effects of Pec on neuro-inflammation are still largely unknown. In this study, the anti-inflammatory effects of Pec in LPS-stimulated murine microglial cell line BV2 were investigated, and the underlying mechanisms were further elucidated.