Glycyrrhizin Alleviates Neuroinflammation and Memory Deficit Induced by Systemic Lipopolysaccharide Treatment in Mice

Abstract

Abstract:The present study investigated the effects of glycyrrhizin (GRZ) on neuroinflammation and memory deficit in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of GRZ was orally administered (10, 30, or 50 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. At 24 h after the LPS injection, GRZ significantly reduced TNF-α and IL-1β mRNA at doses of 30 and 50 mg/kg. COX-2 and iNOS protein expressions were significantly reduced by GRZ at doses of 30 and 50 mg/kg. In the Morris water maze test, GRZ (30 mg/kg) significantly prolonged the swimming time spent in the target and peri-target zones. GRZ also significantly increased the target heading and memory score numbers. In the hippocampal tissue, GRZ significantly reduced the up-regulated Iba1 protein expression and the average cell size of Iba1-expressing microglia induced by LPS. The results indicate that GRZ ameliorated the memory deficit induced by systemic LPS treatment and the effect of GRZ was found to be mediated through the inhibition of pro-inflammatory mediators and microglial activation in the brain tissue. This study supports that GRZ may be a putative therapeutic drug on neurodegenerative diseases associated with cognitive deficits and neuroinflammation such as Alzheimer's disease.

Behavioral and monoamine perturbations in adult male mice with chronic inflammation induced by repeated peripheral lipopolysaccharide administration

“…Increased familiarity of the open field test environment over repeated test sessions may reflect a form of recognition memory [76]. Significant reduction in recognition memory following acute peripheral LPS administration has been demonstrated in several animal studies [77–79]. In this regard, the decreased long-term habituation over repeated open field testing exhibited by LPS-treated mice in this study could be due to the LPS-induced deficits in recognition memory; this needs to be verified by further testing.…”

Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s Disease (AD): From Risk Factors to Therapeutic Targeting

“…Although the therapeutic effect of glycyrrhizin has not been demonstrated in AD mice with developed Aβ pathology, its effects have been extensively evaluated against several AD-like pathologies such as LPS-induced neuroinflammation and cognitive deficits, as well as in surgery-induced cognitive decline. Glycyrrhizin and its derivatives have exerted promising effects mainly by inhibiting HMGB1, improving memory deficits, and reducing the levels of inflammatory cytokines [108][109][110]. The experimental studies with promising outcomes upon HMGB1 inhibition in AD-like pathologies are summarized in Table 1.…”

Tumor Necrosis Factor Alpha: A Major Cytokine of Brain Neuroinflammation

“…Inflammation is a classical host defense response of vascularized living tissue to infection and injury, and in the central nervous system (CNS), the term neuroinflammation is used to denote cellular and inflammatory responses of vascularized neuronal tissue through activation of resident cells in the brain (microglia, astrocytes, and endothelial cells), the recruitment of blood-derived leukocytes including neutrophils, lymphocytes, and macrophages, and a plethora of humoral factors [6,7]. More appropriately, neuroinflammation is a term used to denote inflammation associated with the brain and is characterized by the activation of microglia and expression of major inflammatory mediators without typical features of peripheral inflammation such as edema and neutrophil infiltration [8]. Neuroinflammation in the brain supposedly has a positive effect such as increasing blood flow and removal of damaged tissue by phagocytosis, but in a disease state, the resulting inappropriate inflammation caused negative effects which by far out weight the positive effect [6].…”