4 / 10
Page 42
conferenceseries
.com
Volume 7, Issue 5 (Suppl)
J Clin Exp Pathol
ISSN: 2161-0681 JCEP, an open access journal
Pathology Congress 2017
November 13-14, 2017
NOVEMBER 13-14, 2017 OSAKA, JAPAN
14
th
Asia Pacific Pathology Congress
Inhibition of HBV replication and HBV-related inflammatory responses by KCT-01 through suppression
of cccDNA formation
Eungyeong Jang
1
, Na-Rae Lee
2
, Kyung-Tae Lee
2
, Bum-Joon Kim
3
, Jang-Hoon Lee
1
and Kyung-Soo Inn
2
1
Kyung Hee University, Republic of Korea
2
Kyung Hee University, Republic of Korea
3
Seoul National University, Republic of Korea
C
hronic hepatitis B (CHB) remains incurable because hepatitis B virus (HBV) nuclear covalently closed circular DNA
(cccDNA) undergoes persistent maintenance in hepatocytes. Due to the fact that no current antiviral strategies with
nucleos(t)ide analogs or interferon completely eradicate cccDNA, a novel antiviral option to suppress effectively cccDNA
formation is urgently required. KCT-01 is a newly developed herbal mixture consisted of
Artemisia capillaris, Sanguisorba
officinalis
, and
Curcuma longa
, which each plant has been revealed to cure viral infection and hepatic inflammation in previous
studies. Thus, we investigated whether KCT-01 inhibits HBV virion replication as well as HBV-related hepatic inflammation
through inhibition of cccDNA levels using HepG2.2.15 cell line and HBV hydrodynamic injection mouse model. KCT-01
significantly reduced HBsAg production, virion particle excretion, and intracellular 3.5 kb pregenomic RNA (pgRNA) quantity
in HepG2.2.15 cells, which antiviral effects were comparable to entecavir, a representative antiviral. In accordance with
in
vitro
results, KCT-01 administration dose-dependently suppressed HBsAg production and HBV virion excretion in serum
and cccDNA formation and viral DNA levels in the liver tissue were also inhibited in mouse models. Besides, HBV-related
inflammation mediators, such as TNF-α, IL-6, IL-1β, and MCP, were significantly downregulated under the treatment of KCT-
01, validating that it could mediate both viral replication and inflammatory responses induced by HBV pathogen. Furthermore,
KCT-01 produced according to Good Manufacturing Practices(GMP) regulations showed no toxicity in a preclinical study.
Consequently, this study suggests that KCT-01 may play an effective regulatory role for treating CHB through suppression of
cccDNA formation, a major challenge to cure HBV infection.
Biography
Eungyeong Jang completed her MD and PhD from Kyung Hee University in Republic of Korea.
obliviona@naver.comEungyeong Jang et al., J Clin Exp Pathol 2017, 7:5 (Suppl)
DOI: 10.4172/2161-0681-C1-041