Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model.
Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model.
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DOI：
10.1371/journal.pone.0115323
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Murata RM
中科院分区：
文献类型：
--
作者：
Pasetto S;Pardi V;Murata RM
通过性传播感染艾滋病毒仍然是一个巨大的全球健康问题。每年有100多万妇女新感染。杀微生物剂是一种很有希望的预防战略，妇女可以很容易地控制。在新兴疗法中，类黄酮等天然小分子是新活性物质的重要来源。在这项研究中，我们报告了在体外细胞毒性和抗HIV-1和杀微生物剂活性的黄酮类化合物：杨梅素，槲皮素和松属。使用0.01-100 µM浓度对TZM-bl、HeLa、PBMC和H9细胞培养物进行细胞毒性试验。杨梅素的毒性最低，槲皮素和松属素的毒性相对较高。用TZM-bl细胞加HIV-1 BaL（R5嗜性）、H9和PBMC细胞加HIV-1 MN（X4嗜性）和双嗜性（X4 R5）HIV-1 89.6测试抗HIV-1活性。所有的黄酮类化合物都显示出抗HIV活性，虽然杨梅素比槲皮素或松属素更有效。在TZM-bl细胞中，杨梅素抑制≥90%的HIV-1 BaL感染。结果通过类黄酮处理后H9和PBMC细胞上清液中HIV-1 p24抗原的定量来证实。在HIV-1 MN和HIV-189.6感染的H9和PBMC细胞中，杨梅素显示超过80%的抗HIV活性。槲皮素和Pinocembrin在所有实验中均表现出适度的抗HIV活性。测试了杨梅素对HIV-RT的活性，并抑制了49%的酶。使用双腔女性生殖道模型评价杀微生物剂活性。在体外杀微生物剂活性模型中，杨梅素对不同的HIV-1菌株显示出有希望的结果，同时也显示出微不足道的细胞毒性作用。因此，需要对杨梅素进行进一步的研究，以确定其分子靶点，为转基因研究提供坚实的生物学基础。
HIV infection by sexual transmission remains an enormous global health concern. More than 1 million new infections among women occur annually. Microbicides represent a promising prevention strategy that women can easily control. Among emerging therapies, natural small molecules such as flavonoids are an important source of new active substances. In this study we report the in vitro cytotoxicity and anti-HIV-1 and microbicide activity of the following flavonoids: Myricetin, Quercetin and Pinocembrin. Cytotoxicity tests were conducted on TZM-bl, HeLa, PBMC, and H9 cell cultures using 0.01–100 µM concentrations. Myricetin presented the lowest toxic effect, with Quercetin and Pinocembrin relatively more toxic. The anti-HIV-1 activity was tested with TZM-bl cell plus HIV-1 BaL (R5 tropic), H9 and PBMC cells plus HIV-1 MN (X4 tropic), and the dual tropic (X4R5) HIV-1 89.6. All flavonoids showed anti-HIV activity, although Myricetin was more effective than Quercetin or Pinocembrin. In TZM-bl cells, Myricetin inhibited ≥90% of HIV-1 BaL infection. The results were confirmed by quantification of HIV-1 p24 antigen in supernatant from H9 and PBMC cells following flavonoid treatment. In H9 and PBMC cells infected by HIV-1 MN and HIV-1 89.6, Myricetin showed more than 80% anti-HIV activity. Quercetin and Pinocembrin presented modest anti-HIV activity in all experiments. Myricetin activity was tested against HIV-RT and inhibited the enzyme by 49%. Microbicide activities were evaluated using a dual-chamber female genital tract model. In the in vitro microbicide activity model, Myricetin showed promising results against different strains of HIV-1 while also showing insignificant cytotoxic effects. Further studies of Myricetin should be performed to identify its molecular targets in order to provide a solid biological foundation for translational research.
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