Corylin protects LPS-induced sepsis and attenuates LPS-induced inflammatory response

Katsuhiko Suzuki,Yung-Li Hung,Kuo-Feng Hua,Ming-Yii Huang,Chia-Cheng Su,Po-Len Liu,Wei-Chung Cheng,Chi-Shuo Chen,Kun-Hung Shen,Yu-Ting Wang,Shih-Hua Fang,Shu-Chi Wang,Chia-Yang Li

doi:10.1038/srep46299

Abstract

Corylin is a main compound isolated from Psoralea corylifolia L. (Fabaceae). A variety of pharmacological effects such as antioxidant, anti-proliferation, and anti-inflammatory properties of corylin have been reported. Nevertheless, the effect of corylin in microbial infection and sepsis remains unclear. In the present study, we investigated the anti-inflammatory effects of corylin. Our experimental results demonstrated that corylin inhibited the production of TNF-α, IL-6 and NO by both LPS-activated RAW 264.7 cells and LPS-activated murine peritoneal macrophages. Moreover, corylin suppressed the expression levels of iNOS and COX-2, reduced the production of PGE2 and HMGB1, blocked the translocation of HMGB1 from the nucleus to cytosol, and decreased the phosphorylation of MAPKs in LPS-activated RAW 264.7 cells as well as suppressed the activity of NF-κB in LPS-activated J-Blue cells. In addition, the administration of corylin reduced the production of NO and TNF-α, decreased LPS-induced liver damage markers (AST and ALT) and kidney damage markers (BUN and CRE), attenuated infiltration of inflammatory cells and tissue damage of lung, liver and kidney, and enhanced the survival rate of LPS-challenged mice. Taken together, these results show the anti-inflammatory properties of corylin on LPS-induced inflammation and sepsis. Corylin could potentially be a novel anti-inflammatory and immunosuppressive drug candidate in the treatment of sepsis and septic shock.

Highlights

Interleukin-6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3) activity in hepatocarcinoma Hep3B cells[13]
The results revealed that the cell survival rate did not differ significantly when the RAW 264.7 cells were treated with corylin 0~20 μM (Fig. 1A)
Corylin is a main compound that is isolated from Psoralea corylifolia L., has potent antioxidant activity[11] and osteoblastic proliferation-stimulating activity[12]

Summary

Introduction

Interleukin-6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3) activity in hepatocarcinoma Hep3B cells[13]. Activation of the TLR-4 signaling-pathway plays an important role in regulating the secretion of pro-inflammatory cytokines and mediators through its downstream signaling pathway including mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways in macrophages[27]. The MAPK pathways include JUN N-terminal kinase (JNK) 1/2, p38 MAPK and extracellular-signal-regulated kinases (ERK) 1/2 pathways, which play important roles in regulating activation of NF-κBand activator protein-1 (AP-1)[28], and synthesis of pro-inflammatory cytokine and mediator production in response to stimulation of LPS29,30. We investigated the anti-inflammatory effects of corylin on LPS-stimulated RAW 264.7 cells and mouse peritoneal macrophages. Our results demonstrated that corylin suppresses LPS-induced production of pro-inflammatory cytokines and mediators in RAW 264.7 cells and mouse peritoneal macrophages. Administration of corylin protected mice from endotoxin-induced tissue injury and death, and blocked the production of NO and TNF-αin serum of LPS-challenged mice

Methods

Results

Conclusion