Abstract

8-Hydroxydaidzein (8-HD) is a daidzein metabolite isolated from soybeans. This compound has been studied for its anti-proliferation, depigmentation, and antioxidant activities. However, the anti-inflammatory activities of 8-HD are not well-understood. Through its antioxidant effects in ABTS and DPPH assays, 8-HD reduces the production of sodium nitroprusside (SNP)-induced radical oxygen species (ROS). By triggering various Toll-like receptors (TLRs), 8-HD suppresses the inflammatory mediator nitric oxide (NO) without cytotoxicity. We examined the regulatory mechanism of 8-HD in lipopolysaccharide (LPS)-induced conditions. We found that 8-HD diminishes inflammatory gene expression (e.g., inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α) by regulating the transcriptional activities of nuclear factor (NF)-κB and activator protein 1 (AP-1). To find the potential targets of 8-HD, signaling pathways were investigated by immunoblotting analyses. These analyses revealed that 8-HD inhibits the activation of TAK1 and that phosphorylated levels of downstream molecules decrease in sequence. Together, our results demonstrate the antioxidant and anti-inflammatory actions of 8-HD and suggest its potential use in cosmetics or anti-inflammatory drugs.

Highlights

  • The human immune system comprises two arms: innate and adaptive immunity

  • pattern-associated molecular patterns (PAMPs) are recognized by specific pattern-recognition receptors (PRRs)

  • Toll-like receptors (TLRs) recognize a wide range of PAMPs, including lipids, proteins, glycans, and nucleic acids

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Summary

Introduction

Innate immunity is the first barrier faced by invading pathogens. PAMPs are recognized by specific pattern-recognition receptors (PRRs). These include the NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and Toll-like receptors (TLRs). TLRs recognize a wide range of PAMPs, including lipids, proteins, glycans, and nucleic acids. Each TLR recognizes specific ligands [2,3]. When ligands bind to TLRs, inflammatory signaling pathways are activated via nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) [2,4]. Both ddaiadidzezieninandangdenigseteniinstaerienbiaorteranbsifootrmanesdfotrommeodnothoydmrooxnyolhatyeddroanxydladtiehdydraonxdyladteihdymdreotaxbyolalitteeds mtherotaubgohlitceystothcrhoruogmhecPy4to5c0h-droempeenPd4e5n0t-dpeapthewndaeynst[p17a]t.hw8-ahyysd[r1o7x].y8d-ahiyddzreoinxy(d8a-HidDze, iFnig(8u-rHeD1,) Fisigounre 1d)aisdzoeniendmaeidtazbeoinlitme eistaoblaotleidtefirsoomlatfeedrmfreonmtedfersmoyebnetaendss[o1y8b,1e9a]n. Isntuthdiys, wstuedinyv, ewsteigiantvedestthigeaatendti-tinhfle aamnmti-aintoflraymamndataonrytioaxnidanant taicotxividitainest oafc8ti-vHitDiesanodf d8i-sHseDcteadndunddisesrelycitnedg urengduelraltyoirnygmreegcuhlaantiosrmysm. echanisms

Antioxidant Effects of 8-HD
Biochemical Reagents
Cell Culture
DPPH Assays
ABTS Assays
Preparation of mRNA and Semi-Quantitative PCR
Preparation of Whole Cell Lysates and Immunoblotting
4.10. Statistical Analyses
Full Text
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