Anti-inflammatory Effects of Metformin on Neuro-inflammation and NLRP3 Inflammasome Activation in BV-2 Microglial Cells

Abstract

Metformin is a drug used for the treatment of diabetes and is associated with anti-inflammatory reaction, but the underlying mechanism is unclear. In this study, we investigated the effect of metformin on the inflammatory response in BV-2 microglial cells induced by lipopolysaccharide (LPS) and S100 calcium-binding protein A8 (S100A8). The results revealed that metformin significantly attenuated several inflammatory responses in BV-2 microglial cells, including the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin (IL)-6, involved in the activation of Beclin-1, a crucial regulator of autophagy. In addition, metformin inhibited the LPS-induced phosphorylation of ERK. Metformin also suppressed the activation of NOD-like receptor pyrin domain containing 3 inflammasomes composed of NLRP3, caspase-1, and apoptosis-associated speck like protein containing a caspase recruitment domain, which are involved in the innate immune response. Notably, metformin decreased the secretion of S100A8-induced IL-6 production. These findings suggest that metformin alleviates the neuroinflammatory response via autophagy activation.

Metformin pretreatment rescues olfactory memory associated with subependymal zone neurogenesis in a juvenile model of cranial irradiation

“… 28 , 63 , 65 Importantly, metformin preTx has been shown to reduce in vivo microgliosis, NF-κB activity, and levels of tumor necrosis factor alpha (TNF-α), IL-6, and IL-1β in a rodent stroke model, 43 as well as in vitro microglial secretion of TNF-α and IL-6 in the presence of lipopolysaccharide or S100 calcium-binding protein A8. 66 , 67 Thus, understanding the specific factor(s) that regulate NSC behavior has important implications for neuro-regenerative strategies.…”

Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation

“…This way of western blot analysis is well accepted and reliable one. Researchers usually present the relative expression in their test samples either in ratio of control (at the scale of 1) [36–38] or percent of control (at the scale of 100) [39–43]. We have been presenting our western data in previous lab publications in this pattern [27, 28, 32, 33, 44].…”

Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer’s Disease Treatment

“…It has been reported that metformin decreases the levels of IL-1β and IL-6 in APP/PS1 mice [76]. In addition, different studies have highlighted the anti-inflammatory and antioxidant function of metformin, with several pathways playing a key role in the activation of AMPK [147][148][149][150][151][152]. In certain cases, metformin suppresses inflammation and decreases or removes inflammatory factors largely by dependent pathways and often independently of AMPK at the cellular level and elsewhere at the systemic level [148,149].…”

“…According to Ha and colleagues, metformin possesses anti-inflammatory effects [ 147 ]. The neuroinflammatory response requires microglial cells, which are resident phagocytes in the CNS.…”