Effects of cocktail of four local Malaysian medicinal plants (Phyllanthus spp.) against dengue virus 2

Abstract

BackgroundThe absence of commercialized vaccines and antiviral agents against dengue has made the disease a major health concern around the world. With the current dengue virus transmission rate and incidences, the development of antiviral drugs is of vital need. The aim of this project was to evaluate the possibility of developing a local medicinal plant, Phyllanthus as an anti-dengue agent.MethodsCocktail (aqueous and methanolic) extracts were prepared from four species of Phyllanthus (P.amarus, P.niruri, P.urinaria, and P.watsonii) and their polyphenolic compounds were identified via HPLC and LC-MS/MS analysis. MTS assay was then carried out to determine the maximal non-toxic dose (MNTD) of the extracts, followed by screening of the in vitro antiviral activity of aqueous cocktail extracts against DENV2 by means of time-of-addition (pre-, simultaneous and post-) using RT-qPCR. The differentially expressed proteins in the treated and infected cells were analysed with two dimensional gel electrophoresis experiments.ResultsSeveral active compounds including gallic acid, geraniin, syringin, and corilagen have been identified. The MNTD of both aqueous and methanolic extracts on Vero cells were 250.0 μg/ml and 15.63 μg/ml respectively. Phyllanthus showed strongest inhibitory activity against DENV2 with more than 90% of virus reduction in simultaneous treatment. Two-dimensional analysis revealed significantly altered levels of thirteen proteins, which were successfully identified by tandem MS (MS/MS). These altered proteins were involved in several biological processes, including viral entry, viral transcription and translation regulations, cytoskeletal assembly, and cellular metabolisms.ConclusionsPhyllanthus could be potentially developed as an anti-DENV agent.

Anti-Viral Effects of Medicinal Plants in the Management of Dengue: A Systematic Review

“…Natural products have been considered as an important alternative to manage several diseases, such as dengue (Rothan et al, 2014; Lee et al, 2013).…”

“…As authors have demonstrated the antiviral effect of medicinal plants against DENV (Tang et al, 2012; Lee et al, 2013;Rothan et al, 2014), the aim of this study was to review systematically the published research concerning the use of medicinal plants in the management of dengue using the PubMed database. Considering the findings described in the literature, it is hypothesized an antiviral activity against DENV of some medicinal plants.…”

Carica Papaya; A Paired and Alternative Therapy of Dengue Fever

“…In addition to vaccines, every other possible treatment including alternative medicines are being investigated to test their usefulness in controlling this problem. Lee and his co-investigators demonstrated the effectiveness of cocktail extracts prepared from four species of phyllanthus against the DENV [9].…”

Phyllanthus Sp a Local Plant With Multiple Medicinal Properties

“…The maximum non-toxic dose on Vero cells for both aqueous and methanolic extracts were determined to be 250μg/ml and 15.63μg/ml respectively. At these concentrations, Phyllanthus showed strongest inhibitory activity against DENV2 with more than 90% of virus reduction in simultaneous treatment through regulation of various proteins that play important roles in cell-virus attachment, viral entry, viral polyprotein production, viral RNA replication as well as viral assembly and maturation (17,37). Inhibition of the viral entry into the host cell via binding of viral E protein to heparin sulfate during early infection is normally the first point of intervention (34).…”

“…Herpesviridae family consists of at least eight species of single large double stranded DNA enveloped viruses that are pathogenic to humans (16)(17)(18)(19)(20). Among these species, HSV-1 and HSV-2 are more intriguing due to the enormous clinical symptoms that they may manifest, ranging from gingivostomatitis to keratoconjunctivitis, genital disease, encephalitis.…”