Soy isoflavones ameliorate experimental colitis by targeting ERα/NLRP3 inflammasome pathways

Xiaona Gao; Wentao Fan; Lei Tan; Yuanguo Shi; Chenchen Ding; Shuhui Liu; Yufan Miao; Yan Luo; Xizhi Shi; Sarah DeSaeger; Suquan Song

doi:10.1016/j.jnutbio.2020.108438

Soy isoflavones ameliorate experimental colitis by targeting ERα/NLRP3 inflammasome pathways

J Nutr Biochem. 2020 Sep:83:108438. doi: 10.1016/j.jnutbio.2020.108438. Epub 2020 May 28.

Authors

Xiaona Gao¹, Wentao Fan¹, Lei Tan², Yuanguo Shi², Chenchen Ding¹, Shuhui Liu¹, Yufan Miao¹, Yan Luo², Xizhi Shi³, Sarah DeSaeger⁴, Suquan Song⁵

Affiliations

¹ College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing, 210095, China.
² Administration for Market Regulation of Guangdong Province Key Laboratory of Supervision for Edible Agricultural Products, Shenzhen Centre of Inspection and Testing for Agricultural Products, Shenzhen, 518000, China.
³ State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, 315211, China; School of Marine Sciences, Ningbo University, Ningbo, 315211, PR China.
⁴ Centre of Excellence in Mycotoxicology and Public Health, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
⁵ College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address: suquan.song@njau.edu.cn.

PMID: 32563803
DOI: 10.1016/j.jnutbio.2020.108438

Abstract

Soy isoflavones (SIFs) are selective estrogen receptor modulators (SERMs) that have anti-inflammatory activities. Our previous study found that estrogen receptor α (ERα) directly regulates the NLRP3 transcription and NLRP3 inflammasome assembly. Therefore, we hypothesized that SIFs alleviate colitis via an ERα-dependent mechanism by targeting the NLRP3 inflammasome. The influence of SIFs on colitis and the potential mechanisms were thoroughly determined in this study. The results suggested that SIFs ameliorated dextran sodium sulfate (DSS)-induced body weight loss, reduced disease activity index and promoted the recovery of colon pathological damage in mice. Moreover, expression of the NLRP3 inflammasome was significantly inhibited, and the release of IL-1β and IL-18 was suppressed by SIFs. Furthermore, ERα blockade ameliorated DSS-induced inflammatory responses in the intestine, and SIFs markedly suppressed the expression of ERα in a dose-dependent manner. Our study demonstrated that the protective therapeutic action of SIFs on DSS-induced colitis depended on inhibition of ERα and subsequent NLRP3 inflammasome activation, and SIFs are promising therapeutic agents for the treatment of colitis.

Keywords: Colitis; ERα; Inflammation; NLRP3 inflammasome; Soy isoflavones.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / administration & dosage*
Colitis / drug therapy*
Colitis / genetics
Colitis / immunology
Estrogen Receptor alpha / genetics
Estrogen Receptor alpha / immunology*
Glycine max / chemistry
Humans
Inflammasomes / drug effects*
Inflammasomes / genetics
Inflammasomes / immunology
Interleukin-18 / genetics
Interleukin-18 / immunology
Interleukin-1beta / genetics
Interleukin-1beta / immunology
Isoflavones / administration & dosage*
Male
Mice
Mice, Inbred C57BL
NLR Family, Pyrin Domain-Containing 3 Protein / genetics
NLR Family, Pyrin Domain-Containing 3 Protein / immunology*
Plant Extracts / administration & dosage*

Substances

Anti-Inflammatory Agents
Estrogen Receptor alpha
Inflammasomes
Interleukin-18
Interleukin-1beta
Isoflavones
NLR Family, Pyrin Domain-Containing 3 Protein
Plant Extracts