Planta Med
DOI: 10.1055/s-0043-113044
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Curcumin Promotes Apoptosis of Activated Hepatic Stellate Cells by Inhibiting Protein Expression of the MyD88 Pathway

Ya-Jun He1, Kenny Kuchta2, Yan-Mei Deng1, Silke Cameron3, Yu Lin4, Xu-You Liu1, Guo-Ron Ye1, Xia Lv1, Yuta Kobayashi5, Jian-Chang Shu1
  • 1Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
  • 2National Institute of Health Sciences, Division of Pharmacognosy, Phytochemistry and Narcotics, Setagaya-ku, Tokyo, Japan
  • 3Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Germany
  • 4Medical Corporation Soujikai, Osaka, Japan
  • 5Faculty of Medicine, Shimane University, Izumo, Japan
Further Information

Publication History

received 30 October 2016
revised 11 May 2017

accepted 29 May 2017

Publication Date:
19 June 2017 (eFirst)

Abstract

Activation and proliferation of hepatic stellate cells (HSC) play an important role in the progress of liver fibrosis. HSC activation occurs in response to inflammatory cytokines, cellular interactions with immune cells, and morphogenetic signals. The literature hints to a role of the adaptor protein MyD88 in fibrosis. Although curcumin has been shown to exert inhibitory effects on the proliferation of HSC in vitro, its influence on the MyD88 pathway in HSC has remained unclear. Here, we investigated whether curcumin accelerates apoptosis of HSC through the MyD88 pathway. HSC (rat HSC T6) were divided into a control group, MyD88 small interfering RNA (siRNA) group, curcumin group, and curcumin + MyD88 siRNA group. The MyD88 siRNA groups were exposed to siRNA for 48 h. The curcumin groups were cultured in the presence of curcumin for 24 h. Apoptosis was detected by flow cytometry. For Toll-like receptor (TLR) 2 and 4 as well as MyD88 and the dependent factors NF-κB, TNF-α, and IL-1β, mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). For MyD88, protein expression was further observed by Western Blot. Both curcumin and MyD88 siRNA inhibited the mRNA expression of MyD88 pathway-related effectors (TLR2, TLR4, NF-κB, TNF-α, IL-1β) in HSC. Furthermore, both treatments reduced the expression of MyD88 protein in HSC and promoted their apoptosis. These effects were more obvious in the curcumin + MyD88 siRNA group. This study demonstrates that curcumin promotes apoptosis of activated HSC by inhibiting the expression of cytokines related to the MyD88 pathway. It elucidates the possible mechanisms of curcumin in inducing apoptosis of HSC through the MyD88 pathway.