Abstract
Hepatitis B virus (HBV) infection is endemic in Asia and chronic hepatitis B (CHB) is a major public health issue worldwide. Current treatment strategies for CHB are not satisfactory as they induce a low rate of hepatitis B surface antigen (HBsAg) loss. Extracts were prepared from lettuce hydroponically cultivated in solutions containing glycine or nitrate as nitrogen sources. The lettuce extracts exerted potent anti-HBV effects in HepG2 cell lines in vitro, including significant HBsAg inhibition, HBV replication and transcription inhibition, without exerting cytotoxic effects. When used in combination interferon-alpha 2b (IFNα-2b) or lamivudine (3TC), the lettuce extracts synergistically inhibited HBsAg expression and HBV replication. By using differential metabolomics analysis, Luteolin-7-O-glucoside was identified and confirmed as a functional component of the lettuce extracts and exhibited similar anti-HBV activity as the lettuce extracts in vitro. The inhibition rate on HBsAg was up to 77.4%. Moreover, both the lettuce extracts and luteolin-7-O-glucoside functioned as organic antioxidants and, significantly attenuated HBV-induced intracellular reactive oxygen species (ROS) accumulation. Luteolin-7-O-glucoside also normalized ROS-induced mitochondrial membrane potential damage, which suggests luteolin-7-O-glucoside inhibits HBsAg and HBV replication via a mechanism involving the mitochondria. Our findings suggest luteolin-7-O-glucoside may have potential value for clinical application in CHB and may enhance HBsAg and HBV clearance when used as a combination therapy.
Highlights
Hepatitis B virus (HBV) causes transient and chronic infections of the liver
The intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were assessed. This study demonstrates both lettuce extracts and luteolin-7O-glucoside, which we identified as a functional component of the lettuce extracts, exert potent anti-HBV effects and effectively reduce hepatitis B surface antigen (HBsAg) secretion
The effects of the two lettuce extracts cultivated by 9 mM NaNO3 (S11) and 9 mM glycine (S15) on expression of viral antigens were investigated by measuring the rate of HBsAg and hepatitis B e antigen (HBeAg) secretion by HBV-expressing cells
Summary
Hepatitis B virus (HBV) causes transient and chronic infections of the liver. An effective preventive vaccine has been available for more than 30 years, more than 350 million individuals worldwide still have CHB (Curtis et al, 2005). Infected individuals are at high risk for cirrhosis and hepatocellular carcinoma (Buendia, 1992). The HBV vaccine elicits almost no production of protective antibodies in patients with CHB (Trepo et al, 2014). Approved treatments for CHB based on interferons (IFNs) or NAs can effectively decrease HBV viremia. Neither of these monotherapies nor their combination can effectively reduce serum HBsAg, which is a reliable marker of a favorable long-term prognosis (European Association for the Liver, 2012)
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