Sinomenine activation of Nrf2 signaling prevents hyperactive inflammation and kidney injury in a mouse model of obstructive nephropathy

Free Radical Biology & Medicine
Tian QinWangsen Cao

Abstract

Sinomenine is originally derived from medicinal herb and used preferentially in treatment of rheumatoid diseases in Far East regions. SIN has strong anti-inflammatory and immune-regulatory properties, acting mainly through inhibiting NF-kB signaling. Although the upstream target through which SIN affects NF-kB activity is unknown, evidence suggests that SIN might regulate inflammation through Nrf2 signaling. In this study we explored the role of Nrf2 in mediating SIN's anti-inflammation and kidney protection in a mouse model of obstructive nephropathy. We found that SIN is an activator of Nrf2 signaling. It markedly increased Nrf2 protein level, Nrf2 nuclear translocation, Nef2 transcription capacity, and the downstream protein expression. We further demonstrated that SIN activation of Nrf2 is likely due to its repression of the Nrf2 inhibitor Keap1 since it drastically reduced Keap1 protein through the PKC-sensitive ubiquitination-proteasomal degradation. SIN treatment of nephropathy mice effectively reduced the kidney damage and inflammatory responses, balanced renal oxidative stress, and improved the pathological protein expression in an Nrf2 dependent manner. In addition, SIN also Nrf2-dependently modulated macrophage M1/M2...Continue Reading

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Citations

Oct 7, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jun YangWangsen Cao
May 17, 2019·Journal of Toxicologic Pathology·Ayaka SasakiKazuhiko Suzuki
Jun 27, 2019·Annals of the Rheumatic Diseases·Xiaobo ZhuWangsen Cao
Aug 12, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Ming-Ming ZhaoYu Zhang
May 8, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Fangfang BiWangsen Cao
Nov 16, 2019·The Journal of Pharmacy and Pharmacology·Wanqiu WangFengjie Huang
Oct 8, 2020·Cell Death and Differentiation·Fang ChenWangsen Cao
Jun 5, 2020·CNS & Neurological Disorders Drug Targets·Saeed SamarghandianTahereh Farkhondeh
Aug 24, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Suzi LiuFengjie Huang

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