Modulation of Inducible Nitric Oxide Synthase Expression in LPS-Stimulated BV-2 Microglia by Prenylated Chalcones from Cullen corylifolium (L.) Medik. through Inhibition of I-κBα Degradation.

Do Kim,Ji Jeong,Yeong Han,Hua Li,Jae-Ha Ryu,Hwa Lee

doi:10.3390/molecules23010109

Do Kim, Ji Jeong + Show 4 more

Open Access

https://doi.org/10.3390/molecules23010109

Copy DOI

Abstract

The overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) by microglia may cause neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. From the activity-guided purification of Cullen corylifolium (L.) Medik. (syn. Psoralea corylifolia L.), three prenylated chalcones were identified: isobavachalcone (1), bavachromene (2), and kanzonol B (3). These prenylated chalcones showed concentration-dependent inhibitory effects on NO and PGE2 production in lipopolysaccharide (LPS)-activated microglia. Western blotting and RT-PCR analysis demonstrated that these prenylchalcones reduced the expression of protein and mRNA of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-activated microglia. Furthermore, three prenylated chalcones blocked the inhibitory-κBα (I-κBα) degradation and down-regulated nuclear factor κB (NF-κB) level of nucleus in LPS-stimulated BV-2 microglia. Therefore, these prenylated chalcones from Psoralea corylifolia may be beneficial for the treatment of neuro-inflammatory diseases by modulating iNOS and COX-2 expressions in activated microglial cells.

Highlights

Microglia, an innate immune cell and resident phagocyte in the central nervous system (CNS), plays an active role in CNS homeostasis, infection and pathogen defense
These prenylated chalcones from Psoralea corylifolia may be beneficial for the treatment of neuro-inflammatory diseases by modulating inducible nitric oxide synthase (NOS) (iNOS) and COX-2 expressions in activated microglial cells
NO can be produced by three isoforms of nitric oxide synthase (NOS) such as neuronal NOS, endothelial NOS and inducible NOS [4]

Summary

Introduction

An innate immune cell and resident phagocyte in the central nervous system (CNS), plays an active role in CNS homeostasis, infection and pathogen defense. Activated microglia produce pro-inflammatory and neuro-toxic materials such as nitric oxide (NO), prostaglandins (PGs) and superoxide anion [1]. These mediators are involved in the brain injuries and neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis and Parkinson’s disease [2,3]. NO can be produced by three isoforms of nitric oxide synthase (NOS) such as neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) [4]. Many reports have shown that the iNOS and a large amount of NO produced by activated microglia contribute to the progress of neurodegenerative diseases [6]. Its seeds were gynaecological bleeding, vitiligo and psoriasis.

The chemical structures of compounds 1–3

General Information

Cell Culture

Measurement of Nitric Oxide Production

Prostagandin E2 Assay

Western Blot Analysis