Cui Xiao-Xian, Yang Xiao, Wang Hui-Jing, Rong Xing-Yu, Jing Sha, Xie You-Hua, Huang Dan-Feng, Zhao Chao
Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Front Microbiol. 2017 Dec 6;8:2425. doi: 10.3389/fmicb.2017.02425. eCollection 2017.
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 , 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--glucoside was identified and confirmed as a functional component of the lettuce extracts and exhibited similar anti-HBV activity as the lettuce extracts . The inhibition rate on HBsAg was up to 77.4%. Moreover, both the lettuce extracts and luteolin-7--glucoside functioned as organic antioxidants and, significantly attenuated HBV-induced intracellular reactive oxygen species (ROS) accumulation. Luteolin-7--glucoside also normalized ROS-induced mitochondrial membrane potential damage, which suggests luteolin-7--glucoside inhibits HBsAg and HBV replication via a mechanism involving the mitochondria. Our findings suggest luteolin-7--glucoside may have potential value for clinical application in CHB and may enhance HBsAg and HBV clearance when used as a combination therapy.
乙型肝炎病毒（HBV）感染在亚洲呈地方性流行，慢性乙型肝炎（CHB）是全球主要的公共卫生问题。目前CHB的治疗策略并不令人满意，因为它们诱导乙肝表面抗原（HBsAg）丢失率较低。从在含有甘氨酸或硝酸盐作为氮源的溶液中水培种植的生菜中制备提取物。生菜提取物在HepG2细胞系中发挥了强大的抗HBV作用，包括显著抑制HBsAg、抑制HBV复制和转录，且不产生细胞毒性作用。当与干扰素-α 2b（IFNα-2b）或拉米夫定（3TC）联合使用时，生菜提取物协同抑制HBsAg表达和HBV复制。通过差异代谢组学分析，鉴定并确认木犀草素-7-O-葡萄糖苷是生菜提取物的功能成分，并且表现出与生菜提取物相似的抗HBV活性。对HBsAg的抑制率高达77.4%。此外，生菜提取物和木犀草素-7-O-葡萄糖苷均作为有机抗氧化剂发挥作用，并显著减轻HBV诱导的细胞内活性氧（ROS）积累。木犀草素-7-O-葡萄糖苷还使ROS诱导的线粒体膜电位损伤恢复正常，这表明木犀草素-7-O-葡萄糖苷通过涉及线粒体的机制抑制HBsAg和HBV复制。我们的研究结果表明，木犀草素-7-O-葡萄糖苷可能对CHB的临床应用具有潜在价值，并可能在作为联合疗法使用时增强HBsAg和HBV清除率。
