Anti-inflammatory Activity of 8-Hydroxydaidzein in LPS-Stimulated BV2 Microglial Cells via Activation of Nrf2-Antioxidant and Attenuation of Akt/NF-κB-Inflammatory Signaling Pathways, as Well As Inhibition of COX-2 Activity

• DOI: 10.1021/acs.jafc.8b00437
• Publication Date: 2018-05-23T15:17:57Z
• Authors: Pei-Shan Wu; Hsiou-Yu Ding; Jui-Hung Yen; Shu-Fen Chen; Kuan-Han Lee; Ming-Jiuan Wu
• Keywords: Lipopolysaccharides; 0301 basic medicine; 572; Cyclooxygenase 2 Inhibitors; NF-E2-Related Factor 2; Akt; Anti-Inflammatory Agents; NF-kappa B; COX-2; Isoflavones; Nrf2; Antioxidants; Metabolic Detoxication, Phase II; 3. Good health; Mice; 03 medical and health sciences; 616; Animals; Microglia; Reactive Oxygen Species; Proto-Oncogene Proteins c-akt; 8-hydroxydaidzein; Cell Line, Transformed; Signal Transduction

It was demonstrated that isoflavones can cross the blood–brain barrier, making them desirable candidate agents for prevention of neurological symptoms. 8-Hydroxydaidzein (8-OHD, 4′,7,8-trihydoxyisoflavone) is an isoflavone found only in fermented soy food. Current results showed 8-OHD inhibited LPS-stimulated production nitric oxide (NO) and proinflammatory cytokines, such as tumor necrosis factor (TNF)-α interleukin (IL)-6, by inhibiting gene expression BV2 microglial cells. Moreover, markedly quenched reactive oxygen species (ROS) activated NF-E2-related 2 (Nrf2) so to upregulate Phase II enzymes, including heme oxygenase (HO)-1, NAD(P)H quinone dehydrogenase 1 (NQO1), modifier subunit glutamate cysteine ligase (GCLM). also suppressed phosphorylation Akt NF-κB-p65. The anti-inflammatory activity attenuated HO-1 inhibitor zinc protoporphyrin (Znpp) but augmented PI3K/Akt LY294002. diminished LPS-induced prostaglandin E2 (PGE2) without affecting cyclooxygenase (COX)-2 expression. In vitro assay shows displayed mixed-type inhibition COX-2 with IC50 8.9 ± 1.2 μM. These data suggest may be associated activation Nrf2/HO-1 attenuation Akt/NF-κB signaling pathways well enzyme activity. conclusion, 8-OHD, a potent Nrf2 activator, suppressor, inhibitor, have health-promoting effects mitigating microglia preventing neuroinflammation.