Soyasapogenol B and Genistein Attenuate Lipopolysaccharide-Induced Memory Impairment in Mice by the Modulation of NF-κB-Mediated BDNF Expression

Abstract

Lactobacillus plantarum C29-fermented defatted soybean (FDS), which contains soyasaponins such as soyasaponin I (SI) and soyasapogenol B (SB) and isoflavones such as genistin (GE) and genistein (GT), attenuated memory impairment in mice. Moreover, in the preliminary study, FDS and its soyasaponins and isoflavones significantly inhibited NF-κB activation in LPS-stimulated microglial BV2 cells. Therefore, we examined the effects of FDS and its constituents SI, SB, GT, and GE on LPS-induced memory impairment in mice. Oral administration of FDS (80 mg/kg), which has higher concentrations of SB and GE than DS, recovered LPS-impaired cognitive function in Y-maze (55.1 ± 3.5%) and passive avoidance tasks (50.9 ± 19.2 s) to 129.2% (74.1 ± 3.5%) and 114.2% (290.0 ± 22.4 s) of normal mice, respectively (P < 0.05). SB and GE (10 μM) also more potently attenuated LPS-impaired cognitive behavior than SI and GT, respectively. SB (10 mg/kg) was the most effective: treatment recovered LPS-impaired spontaneous alternation and latency time to 105.7% and 126.8% of normal control mice, respectively (P < 0.05). SB and GE significantly increased BDNF expression and CREB phosphorylation in LPS-treated mice and corticosterone-stimulated SH-SY5Y cells. Furthermore, SB and GE (10 μM) also significantly inhibited NF-κB activation in LPS-treated mice. These findings suggested that FDS and its constituent soyasaponins and isoflavones may attenuate memory impairment by the regulation of NF-κB-mediated BDNF expression.

Lactobacillus plantarum C29‐Fermented Soybean (DW2009) Alleviates Memory Impairment in 5XFAD Transgenic Mice by Regulating Microglia Activation and Gut Microbiota Composition

“…A Luminata Forte Western HRP Substrate was purchased from Millipore Corporation (Billerica, MA, USA). FDS (DW2009) and C29 (KCCM10885, Korea Culture Center of Microorganisms, Seoul, Korea) were prepared in DongHwa Pharm according to the method of Lee et al . and the preparation protocol was described in the supplement.…”

“…Brain cortex and hippocampus and colon tissues were removed 2 h after the performance of the final task and homogenized with RIPA lysis buffer with 1% protease inhibitor cocktail and a phosphatase inhibitor cocktail on the ice . The supernatant of the lysates was electrophoresed by SDS‐PAGE and then transferred to a nylon membrane.…”

“…Lactobacillus plantarum C29 increased cognitive function in aged rats and attenuated LPS‐ or scopolamine‐induced memory impairment in mice . C29‐fermented defatted soybean powder (FDS, DW2009) also inhibited gut microbiota LPS production and attenuated LPS‐ or scopolamine‐induced memory impairment in mice . Nevertheless, the memory impairment‐ameliorating mechanism of FDS against AD remains elusive.…”

Protective effects of Genistein on the cognitive deficits induced by chronic sleep deprivation

“…NF-κB is sequestered in the cytoplasm and occupies a vital position in the inflammatory cascade; once under oxidative stress, it translocates into the nucleus and induces various inflammatory proteins such as iNOS and COX-2 (Qiao, Jiang, & Gao, 2018). Moreover, GE was reported to exhibit the neuroprotective effects owing to the anti-inflammatory ability both in vivo and in vitro, that it was able to inhibit LPS-induced NF-κB activation in the hippocampus of mice and inhibit the LPSstimulated TNF-α expression in microglial BV-2 cells (Lee et al, 2017). Besides, the ameliorative property of GE against the metalinduced neurotoxicity was related to its anti-inflammatory property (Sukanya et al, 2018).…”

Improvement in Cognitive Function with Green Soybean Extract May Be Caused by Increased Neuritogenesis and BDNF Expression

“…BDNF is widely expressed in the mammalian brain and is a key mediator involved in both neurogenesis and memory processing [23]. Soybean isoflavones have been found to promote the activity of neurotrophic factors such as BDNF and nerve growth factor in the brain [24][25][26]. Genistein and daidzein at 0.02-2 µM significantly promoted hippocampus neuronal cell viability and proliferation in the H19-7 neural cell line [27].…”