TY - JOUR
T1 - Inhibitory effect of silibinin on hepatitis B virus entry
AU - Umetsu, Teruyuki
AU - Inoue, Jun
AU - Kogure, Takayuki
AU - Kakazu, Eiji
AU - Ninomiya, Masashi
AU - Iwata, Tomoaki
AU - Takai, Satoshi
AU - Nakamura, Takuya
AU - Sano, Akitoshi
AU - Shimosegawa, Tooru
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan ( 15K08981 ).
Publisher Copyright:
© 2018 The Authors
PY - 2018/7
Y1 - 2018/7
N2 - Hepatitis B virus (HBV) infection is a worldwide health problem because of its potential to cause liver cirrhosis and hepatocellular carcinoma. Silibinin is a constituent of an extract of milk thistle, which is empirically used as a herbal medicine for the protection of liver, but its detailed effects on HBV are unknown. Because a previous study reported that silibinin hinders clathlin-mediated endocytosis (CME), we aimed to test whether silibinin inhibits the entry of HBV into hepatocytes. Using HepG2-NTCP-C4 cells, which overexpress sodium taurocholate cotransporting polypeptide (NTCP), it was shown that silibinin inhibited HBV infection dose-dependently. Similar effects were observed using human primary hepatocytes (PXB-cells). Additionally, a combination of silibinin and entecavir reduced HBV DNA in the culture supernatant more than either mono-treatment alone in HepG2-NTCP-C4 cells that had already been infected with HBV. Silibinin decreased transferrin uptake but did not affect the interaction between the HBV envelope and NTCP, suggesting that silibinin might inhibit HBV infection by hindering CME. In conclusion, this study showed that silibinin inhibits HBV entry in vitro.
AB - Hepatitis B virus (HBV) infection is a worldwide health problem because of its potential to cause liver cirrhosis and hepatocellular carcinoma. Silibinin is a constituent of an extract of milk thistle, which is empirically used as a herbal medicine for the protection of liver, but its detailed effects on HBV are unknown. Because a previous study reported that silibinin hinders clathlin-mediated endocytosis (CME), we aimed to test whether silibinin inhibits the entry of HBV into hepatocytes. Using HepG2-NTCP-C4 cells, which overexpress sodium taurocholate cotransporting polypeptide (NTCP), it was shown that silibinin inhibited HBV infection dose-dependently. Similar effects were observed using human primary hepatocytes (PXB-cells). Additionally, a combination of silibinin and entecavir reduced HBV DNA in the culture supernatant more than either mono-treatment alone in HepG2-NTCP-C4 cells that had already been infected with HBV. Silibinin decreased transferrin uptake but did not affect the interaction between the HBV envelope and NTCP, suggesting that silibinin might inhibit HBV infection by hindering CME. In conclusion, this study showed that silibinin inhibits HBV entry in vitro.
KW - Clathrin-mediated endocytosis
KW - HBV
KW - Herbal medicine
UR - http://www.scopus.com/inward/record.url?scp=85056403753&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056403753&partnerID=8YFLogxK
U2 - 10.1016/j.bbrep.2018.03.003
DO - 10.1016/j.bbrep.2018.03.003
M3 - Article
AN - SCOPUS:85056403753
SN - 2405-5808
VL - 14
SP - 20
EP - 25
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
ER -
