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Virus Res. 2016 Apr 2;215:104-13. doi: 10.1016/j.virusres.2015.12.005. Epub 2015 Dec 9.

Anti-hepatitis B virus effect of matrine-type alkaloid and involvement of p38 mitogen-activated protein kinase and tumor necrosis factor receptor-associated factor 6.

Author information

1
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China; China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China.
2
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China. Electronic address: shenhonghui@hotmail.com.
3
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China.
4
Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, China.
5
Chengde Medical University, Chengde, Hebei 067000, China.
6
Research Center of Clinical Medicine, 302 Military Hospital, Beijing 100039, China.
7
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China. Electronic address: zouwenjun@vip.163.com.
8
Integrative Medical Center, 302 Military Hospital, Beijing 100039, China. Electronic address: pharmacy302@126.com.

Abstract

The matrine-type alkaloid, oxymatrine inhibits hepatitis B virus (HBV) replication but very little is known about these effects in other matrine-type alkaloids, including sophoridine and sophocarpine. Therefore, we compared the in vitro anti-HBV effects of matrine, oxymatrine, sophocarpine, and sophoridine by treating an HBV-transfected cell line (HepG2.2.15) with 0.4-1.6mM of the compounds for 24 or 72h. The levels of the HBV surface antigen (HBsAg) and e antigen (HBeAg) in the culture medium, as well as the intracellular and extracellular HBV DNA levels, were determined. Metabolomic analysis and detection of the mRNA level of p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor receptor-associated factor (TRAF) 6, extracellular signal-regulated kinase (ERK) 1, NOD-like receptor family pyrin domain containing 10 (NLRP10), and caspase-1 were conducted in sophoridine-treated HepG2.2.15 cells. HepG2.2.15 cell exposure to 0.4-1.6mM sophocarpine or sophoridine for 24h reduced the HBsAg level of the medium more effectively than exposure to matrine and oxymatrine did, and reduced the HBeAg levels more effectively than these compounds did at 1.6mM. Sophoridine (0.4-1.6mM) reduced the cell medium HBV DNA levels more than the same concentrations of matrine, oxymatrine, or sophocarpine did. After 72h, 0.4 and 0.8mM sophoridine reduced HBsAg and intracellular HBV DNA levels more potently than matrine, oxymatrine, or sophocarpine did. Furthermore, sophoridine (0.8mM) potently reduced the cell medium HBeAg levels while the metabolomic analyses revealed that HepG2.2.15 cells exposed to 0.8mM sophoridine for 72h exhibited reduced cycloleucine and phytosphingosine levels. In addition, the mRNA expression analyses revealed that HepG2.2.15 cells exposed to 0.8mM sophoridine showed reduced levels of p38 MAPK, TRAF6, ERK1, NLRP10, and caspase-1. Sophoridine produced more potent anti-HBV effects than matrine, oxymatrine, and sophocarpine did. These effects may be related to the sophoridine-mediated reduction of p38 MAPK and TRAF6 levels.

KEYWORDS:

Hepatitis B virus; NLRP10; Sophoridine; Tumor necrosis factor receptor-associated factor 6; p38 Mitogen-activated protein kinase

PMID:
26685094
DOI:
10.1016/j.virusres.2015.12.005
[Indexed for MEDLINE]

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