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Abstract

Chronic 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-�±, IL-6, IL-1�², and MCP, were significantly downregulated under the treatment of KCT01, 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.