Nutan, SK and Modi, M and Dezzutti, CS and Kulshreshtha, S and Rawat, AKS and Srivastava, SK and Malhotra, S and Verma, A and Ranga, U and Gupta, SK
(2013)
Extracts from Acacia catechu suppress HIV-1 replication by inhibiting the activities of the viral protease and Tat.
Virology Journal, 10.
Abstract
Background: Acacia catechu (Mimosa family) stem bark extracts have been used traditionally as a dietary supplement as well as a folk medicine given its reported anti-inflammatory, immunomodulatory, hepatoprotective, antioxidant, anti-microbial and anti-tumor activities. The present study was undertaken to evaluate the anti-HIV-1 activity of the extracts from stem bark of A. catechu. Methods. The aqueous and 50% ethanolic extracts of A. catechu stem bark were prepared and 50% ethanolic extract was further fractioned by successively partitioning with petroleum ether, chloroform and n-butanol. All the extracts and fractions were evaluated for cytotoxicity and anti-HIV-1 activity using different in vitro assays. The active n-butanol fraction was evaluated for its inhibition against HIV-1 reverse transcriptase, integrase, protease, pro-viral genome integration and viral Tat protein mediated transactivation. The effect of n-butanol fraction on the induction of pro-inflammatory cytokines secretion in Vk2/E6E7 cells and transepithelial resistance in Caco-2 and HEC-1A cells was investigated. Results: The aqueous and 50% ethanolic extracts of A. catechu showed IC§ssub§50§esub§ values of 1.8 ± 0.18 μg/ml and 3.6 ± 0.31 μg/ml, respectively in cell-free virus based assay using TZM-bl cells and HIV-1§ssub§NL4.3§esub§ (X-4 tropic). In the above assay, n-butanol fraction exhibited anti-HIV-1 activity with an IC§ssub§50§esub§ of 1.7 ± 0.12 μg/ml. The n-butanol fraction showed a dose-dependent inhibition against HIV-1§ssub§NL4.3§esub§ infection of the peripheral blood lymphocytes and against HIV-1§ssub§BaL§esub§(R-5-tropic) as well as two different primary viral isolates of HIV-1 infection of TZM-bl cells. The n-butanol fraction demonstrates a potent inhibitory activity against the viral protease (IC§ssub§50§esub§ = 12.9 μg/ml), but not reverse transcriptase or integrase. Further, in Alu-PCR no effect on viral integration was observed. The n-butanol fraction interfered with the Tat-mediated Long Terminal Repeat transactivation in TZM-bl cells, mRNA quantitation (qRT-PCR) and electrophoretic mobility shift assay (EMSA). The n-butanol fraction did not cause an enhanced secretion of pro-inflammatory cytokines in Vk2/E6E7 cells. Additionally, no adverse effects were observed to the monolayer formed by the Caco-2 and HEC-1A epithelial cells. Conclusions: The results presented here show a potential anti-HIV-1 activity of A. catechu mediated by the inhibition of the functions of the viral protein and Tat. © 2013 Nutan et al.; licensee BioMed Central Ltd.
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| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Nutan, SK | | | | | Modi, M | | | | | Dezzutti, CS | csd13@pitt.edu | CSD13 | | | Kulshreshtha, S | | | | | Rawat, AKS | | | | | Srivastava, SK | | | | | Malhotra, S | | | | | Verma, A | | | | | Ranga, U | | | | | Gupta, SK | | | |
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| Centers: |
Other Centers, Institutes, Offices, or Units > Magee-Women's Research Institute |
| Date: |
22 October 2013 |
| Date Type: |
Publication |
| Journal or Publication Title: |
Virology Journal |
| Volume: |
10 |
| DOI or Unique Handle: |
10.1186/1743-422x-10-309 |
| Refereed: |
Yes |
| Date Deposited: |
02 Dec 2016 16:09 |
| Last Modified: |
26 Jan 2019 19:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/29665 |
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