Luteolin-7-O-Glucoside Present in Lettuce Extracts Inhibits Hepatitis B Surface Antigen Production and Viral Replication by Human Hepatoma Cells in Vitro.

Luteolin-7-O-Glucoside Present in Lettuce Extracts Inhibits Hepatitis B Surface Antigen Production and Viral Replication by Human Hepatoma Cells in Vitro.
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生菜提取物中的 Luteolin-7-O-Glucoside 可在体外抑制人肝癌细胞产生乙型肝炎表面抗原和病毒复制。

DOI:
10.3389/fmicb.2017.02425
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发表时间:
2017
影响因子:
5.2
通讯作者:
Zhao C
Zhao C
中科院分区:
生物学2区
文献类型:
--
作者:
Cui XX;Yang X;Wang HJ;Rong XY;Jing S;Xie YH;Huang DF;Zhao C

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B型肝炎病毒(HBV)感染是亚洲的地方病,慢性B型肝炎(CH B)是世界范围内的主要公共卫生问题。目前CH B的治疗策略并不令人满意,因为它们诱导的B型肝炎表面抗原(HBsAg)丢失率低。提取物是从生菜水培含有甘氨酸或硝酸盐作为氮源的解决方案。莴苣提取物在体外HepG 2细胞系中产生有效的抗HBV作用,包括显著的HBsAg抑制、HBV复制和转录抑制,而不产生细胞毒性作用。当与干扰素-α 2b(IFNα-2b)或拉米夫定(3 TC)联合使用时,莴苣提取物协同抑制HBsAg表达和HBV复制。通过差异代谢组学分析,木犀草素-7-O-葡萄糖苷被鉴定和确认为莴苣提取物的功能成分,并表现出与莴苣提取物相似的体外抗HBV活性。对HBsAg的抑制率达77.4%。此外,莴苣提取物和木犀草素-7-O-葡萄糖苷作为有机抗氧化剂,显着衰减HBV诱导的细胞内活性氧(ROS)的积累。木犀草素-7-O-葡萄糖苷也使ROS诱导的线粒体膜电位损伤正常化,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,毛地黄黄酮-7-O-葡萄糖苷可能有潜在的临床应用价值,在慢性乙型肝炎,并可能提高HBsAg和HBV清除时,作为联合治疗。
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.
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