姜黄素抑制所有丙型肝炎病毒基因型进入人肝细胞
Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells

肠道。2014年7月,63(7):1137 - 49。
Anggakusuma, Colpitts CC, Schang LM, Rachmawati H, Frentzen A, Pfaender S, Behrendt P, Brown RJ, Bankwitz D, Steinmann J, Ott M, Meuleman P, Rice CM, Ploss A, Pietschmann T, Steinmann E。
摘要

目的:
丙型肝炎病毒(HCV)感染可导致严重的肝病，并影响全球1.6亿人。接受肝器官移植的人们面临着移植器官的普遍再次感染。因此，迫切需要针对感染早期的廉价抗病毒策略，以防止HCV感染的复发。本研究的目的是确定姜黄素作为HCV进入抑制剂的效力。

设计:
采用HCV伪粒子(HCVpp)和细胞培养衍生的HCV (HCVcc)对姜黄素及其衍生物在肝癌细胞系和原发性人肝细胞中的抗病毒活性进行了评价。采用r18标记的病毒粒子和膜流动性试验对其作用机理进行了分析。

结果:
姜黄素治疗对HCV RNA复制或病毒组装/释放无影响。然而，HCV与姜黄素共孵育能有效抑制所有主要HCV基因型的进入。除了tetrahydrocurcumin，其它姜黄素衍生品也有类似的抗病毒活动,表明α,β-unsaturated酮组抗病毒活性的重要性。已知的丙肝病毒受体的表达水平未发生改变，而使用该化合物预处理则减少了病毒的传染性，而没有发生病毒裂解。膜流动性实验表明，姜黄素影响HCV包膜的流动性，导致病毒结合和融合能力下降。姜黄素还被发现可以抑制细胞间的传播，并与其他抗病毒药物联合有效。

结论:
姜黄姜黄素通过影响细胞膜的流动性从而削弱病毒的结合和融合，从而独立于基因型和原发性人肝细胞抑制HCV的进入。

　

Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells

Gut. 2014 Jul;63(7):1137-49.
Anggakusuma, Colpitts CC, Schang LM, Rachmawati H, Frentzen A, Pfaender S, Behrendt P, Brown RJ, Bankwitz D, Steinmann J, Ott M, Meuleman P, Rice CM, Ploss A, Pietschmann T, Steinmann E.

Abstract
OBJECTIVE:
Hepatitis C virus (HCV) infection causes severe liver disease and affects more than 160 million individuals worldwide. People undergoing liver organ transplantation face universal re-infection of the graft. Therefore, affordable antiviral strategies targeting the early stages of infection are urgently needed to prevent the recurrence of HCV infection. The aim of the study was to determine the potency of turmeric curcumin as an HCV entry inhibitor.

DESIGN:
The antiviral activity of curcumin and its derivatives was evaluated using HCV pseudo-particles (HCVpp) and cell-culture-derived HCV (HCVcc) in hepatoma cell lines and primary human hepatocytes. The mechanism of action was dissected using R18-labelled virions and a membrane fluidity assay.

RESULTS:
Curcumin treatment had no effect on HCV RNA replication or viral assembly/release. However, co-incubation of HCV with curcumin potently inhibited entry of all major HCV genotypes. Similar antiviral activities were also exerted by other curcumin derivatives but not by tetrahydrocurcumin, suggesting the importance of α,β-unsaturated ketone groups for the antiviral activity. Expression levels of known HCV receptors were unaltered, while pretreating the virus with the compound reduced viral infectivity without viral lysis. Membrane fluidity experiments indicated that curcumin affected the fluidity of the HCV envelope resulting in impairment of viral binding and fusion. Curcumin has also been found to inhibit cell-to-cell transmission and to be effective in combination with other antiviral agents.

CONCLUSIONS:
Turmeric curcumin inhibits HCV entry independently of the genotype and in primary human hepatocytes by affecting membrane fluidity thereby impairing virus binding and fusion.

Comment in
Curcumin against hepatitis C virus infection: spicing up antiviral therapies with 'nutraceuticals'? [Gut. 2014]
PMID: 23903236 DOI: 10.1136/gutjnl-2012-304299
[Indexed for MEDLINE]

https://www.ncbi.nlm.nih.gov/pubmed/23903236/