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Biomedicine and pharmacotherapy
Volume 109
pages 322-332 (janvier 2019)
Doi : 10.1016/j.biopha.2018.10.054
Received : 7 July 2018 ;  accepted : 10 October 2018
Original Articles

A proteomic analysis of the anti-dengue virus activity of andrographolide
 

Atchara Paemanee a, b, Atitaya Hitakarun a, Phitchayapak Wintachai a, Sittiruk Roytrakul b, Duncan R. Smith a,
a Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, 25/25 Phuttamonthon Sai 4, Salaya, Nakorn Pathom 73170, Thailand 
b 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 

Corresponding author at: Institute of Molecular Biosciences, Mahidol University, Salaya Campus, 25/25 Phuttamonton Sai 4, Salaya, 73170 Nakorn Pathom, Thailand.Institute of Molecular BiosciencesMahidol UniversitySalaya Campus25/25 Phuttamonton Sai 4SalayaNakorn Pathom73170Thailand
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The full text of this article is available in PDF format.
Highlights

Proteomic analysis was used to investigate the anti-DENV activity of andrographolide
Identified proteins included chaperone proteins including GRP78
Increased phosphorylation of PERK and eIF2α was observed
The antiviral activity of andrographolide may result from its action on GRP78

The full text of this article is available in PDF format.
Abstract

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.

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Keywords : Andrographolide, Dengue virus, Glucose regulated protein 78, Proteomics




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