穿心莲内酯抗登革病毒活性的蛋白质组学分析。
A proteomic analysis of the anti-dengue virus activity of andrographolide.
机构信息
Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, 25/25 Phuttamonthon Sai 4, Salaya, Nakorn Pathom 73170, Thailand; Proteomics Research Laboratory, Genome Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 113 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathumthani 12120, Thailand.
Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, 25/25 Phuttamonthon Sai 4, Salaya, Nakorn Pathom 73170, Thailand.
出版信息
Biomed Pharmacother. 2019 Jan;109:322-332. doi: 10.1016/j.biopha.2018.10.054. Epub 2018 Nov 3.
Andrographolide is a major bioactive constituent of Andrographis paniculata that has been shown in vitro to have antiviral activity against a number of viruses, including the mosquito transmitted dengue virus (DENV). However, how andrographolide exerts an anti-DENV effect remains unclear. This study therefore sought to further understand the mechanism of action of andrographolide in inhibiting DENV infection of liver cells using a proteomic based approach. Both 1 dimension (D) and 2D proteome systems were used. Initial data was generated through andrographolide treatment of HepG2 cells without DENV infection (1D analysis), while subsequent data was generated through a combination of andrographolide treatment and DENV infection (2D analysis). A total of 17 (1D) and 18 (2D) proteins were identified as differentially regulated. The analyses identified proteins involved in chaperone activities, as well as energy production. In particular evidence suggested an important role for GRP78 and the unfolded protein response in mediating the anti-DENV activity of andrographolide, which might, in part, explain the broad antiviral activity of andrographolide.
穿心莲内酯是穿心莲的主要生物活性成分，体外实验表明它具有抗多种病毒的活性，包括蚊虫传播的登革热病毒（DENV）。然而，穿心莲内酯如何发挥抗 DENV 作用尚不清楚。因此，本研究采用基于蛋白质组学的方法，进一步研究穿心莲内酯抑制肝细胞感染 DENV 的作用机制。使用了一维（1D）和二维（2D）蛋白质组系统。最初的数据是通过未感染 DENV 的 HepG2 细胞用穿心莲内酯处理生成的（1D 分析），而随后的数据是通过穿心莲内酯处理和 DENV 感染的组合生成的（2D 分析）。共鉴定出 17 种（1D）和 18 种（2D）差异调节蛋白。分析鉴定出与伴侣蛋白活性和能量产生相关的蛋白。特别是有证据表明，GRP78 和未折叠蛋白反应在介导穿心莲内酯的抗 DENV 活性中起着重要作用，这可能部分解释了穿心莲内酯广泛的抗病毒活性。
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