A cardiac glucoside with<i>in vitro</i>anti-HIV activity isolated from<i>Elaeodendron croceum</i>

Prinsloo, Gerhard; Meyer, J.J.M.; Hussein, Ahmed A.; Muñóz, Eduardo; Sanchez, Rocio

doi:10.1080/14786410903211912

Cited by 18 publications

(20 citation statements)

References 6 publications

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“…The possibility of repurposing drugs already used in humans as novel therapeutics for the control of HIV-1 infection is highly attractive. Our findings agree with a recent study which identified multiple CSs as inhibitors of HIV-1 expression 45 , 51 . Our study confirms that ≥ 5 of the reported hits and 7 additional CSs suppress HIV-1 gene expression in transformed cells [HeLa and CD4 + SUPT1s, Supplementary Figs S2 (or Fig.…”

Section: Discussionsupporting

confidence: 93%

Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1/2-ERK1/2 signaling

Wong

Lingwood

Ostrowski

et al. 2018

Sci Rep

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The capacity of HIV-1 to develop resistance to current drugs calls for innovative strategies to control this infection. We aimed at developing novel inhibitors of HIV-1 replication by targeting viral RNA processing—a stage dependent on conserved host processes. We previously reported that digoxin is a potent inhibitor of this stage. Herein, we identify 12 other cardiac glycoside/aglycones or cardiotonic steroids (CSs) that impede HIV growth in HIV-infected T cells from clinical patients at IC50s (1.1–1.3 nM) that are 2–26 times below concentrations used in patients with heart conditions. We subsequently demonstrate that CSs inhibit HIV-1 gene expression in part through modulation of MEK1/2-ERK1/2 signaling via interaction with the Na+/K+-ATPase, independent of alterations in intracellular Ca2+. Supporting this hypothesis, depletion of the Na+/K+-ATPase or addition of a MEK1/2-ERK1/2 activator also impairs HIV-1 gene expression. Similar to digoxin, all CSs tested induce oversplicing of HIV-1 RNAs, reducing unspliced (Gag) and singly spliced RNAs (Env/p14-Tat) encoding essential HIV-1 structural/regulatory proteins. Furthermore, all CSs cause nuclear retention of genomic/unspliced RNAs, supporting viral RNA processing as the underlying mechanism for their disruption of HIV-1 replication. These findings call for further in vivo validation and supports the targeting of cellular processes to control HIV-1 infection.

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Section: Discussionsupporting

confidence: 93%

Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1/2-ERK1/2 signaling

Wong

Lingwood

Ostrowski

et al. 2018

Sci Rep

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“…); saffraan, bossafraan (Afr.) Leaves, bark, roots Cleaning of the digestive tract, chest congestion [ 34 , 35 ]. PRU 120127 Morus mesozygia Moraceae Black mulberry or African mulberry Leaves, bark, roots Arthritis, debility, malnutrition, gastroenteritis, rheumatism, venereal diseases, wound infections, dermatitis, syphilis, malaria, fever, pain, depression, peptic ulcers [ 48 ] PRU 120128 …”

Section: Methodsmentioning

confidence: 99%

The efficacy and safety of nine South African medicinal plants in controlling Bacillus anthracis Sterne vaccine strain

Elisha

Dzoyem

Botha

et al. 2015

BMC Complement Altern Med

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BackgroundAnthrax is a zoonotic disease caused by Bacillus anthracis, a Gram-positive spore-forming bacterium. The presence of the bacteria and the toxins in the blood of infected hosts trigger a cascade of pathological events leading to death. Nine medicinal plants with good activities against other bacteria were selected to determine their in vitro antibacterial activity against Bacillus anthracis Sterne strain. The cytotoxicity of the extracts on Vero kidney cells was also determined.ResultsThe minimum inhibitory concentration (MIC) values of the extracts against Bacillus anthracis Sterne strain ranged from 0.02 to 0.31 mg/ml. Excellent MIC values were observed for the following plant species: Maesa lanceolata (0.02 mg/ml), Bolusanthus speciosus, Hypericum roeperianum, Morus mesozygia (0.04 mg/ml) and Pittosporum viridiflorum (0.08 mg/ml). The total antibacterial activity of the extracts ranged from 92 to 5562 ml/g. Total activity presents the volume to which the extract from 1 g of plant material can be diluted and still inhibit microbial growth. Maesa lanceolata and Hypericum roeperianum had the highest total activity with values of 5562 and 2999 ml/g respectively. The extracts of Calpurnia aurea had the lowest total activity (92 ml/g). The cytotoxicity determined on Vero cells indicated that most of the extracts were relatively non-toxic compared to doxorubicin (LC50 8.3 ± 1.76 μg/ml), except for the extracts of Maesa lanceolata, Elaeodendron croceum and Calpurnia aurea with LC50 values at 2.38 ± 0.25, 5.20 ± 0.24 and 13 ± 2.26 μg/ml respectively. The selectivity index (SI) ranged from 0.02 to 1.66. Hypericum roeperianum had the best selectivity index, (SI = 1.66) and Elaeodendron croceum had lowest value (SI = 0.02).ConclusionsThe crude acetone extracts of the selected plant species had promising antibacterial activity against Bacillus anthracis. Maesa lanceolata extracts could be useful as a disinfectant and Hypericum roeperianum could be useful to protect animals based on its high total activity and selectivity index. Further investigation of these plant extracts may lead to the development of new therapeutic agents to protect humans or animals against anthrax.

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“…Compounds stabilizing the firefly luciferase reporter protein give false positives. (Auld et al, 2008;Cos et al, 2002;Ngwira et al, 2015;Prinsloo et al, 2010;Shoemaker et al, 2004;Sotoca et al, 2010;Wang et al, 2014) NF-κB activation assay Cells are stably transfected with a plasmid containing the firefly luciferase gene driven by the HIV-LTRpromoter, highly dependent on NF-κB activation induced by TNFα. High expression of luciferase activity reflects NF-κB activation through the canonical pathway.…”

Section: Constituents With Antioxidant Activity Results In Toomentioning

confidence: 99%

“…Thereby, upon infection with HIV, the reporter gene will be induced in a quantifiable fashion as beta galactosidase allows quantification of inhibitory effects of compounds or extracts (Lubbe et al, 2012). HIV-1 pseudovirions and viruses has been used (Ngwira et al, 2015;Prinsloo et al, 2010;Wang et al, 2014) and Hela-Tat-Luc cells that are stably transfected with for instance a plasmid pcDNA3-TAT together with a reporter plasmid LTR-Luc indicates protein activation. Therefore the HIV-1 LTR is highly activated in this cell line as a consequence of high levels of intracellular Tat protein (Tshikalange et al, 2008b).…”

Section: Constituents With Antioxidant Activity Results In Toomentioning

confidence: 99%

Anti-HIV activity of southern African plants: Current developments, phytochemistry and future research

Prinsloo

Marokane

Street

2018

Journal of Ethnopharmacology

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An investigation of the plants from southern Africa with ethnobotanical use for the treatment of HIV, management of HIV or HIV-related symptoms, therefore provide a very good analysis of the major assays employed and the anti-viral compounds and compound groups identified. The similarity in identified anti-viral compounds worldwide should support the progression from in vitro studies to in vivo testing in development of affordable and effective anti-HIV agents for countries with high infection and mortality rates due to HIV/AIDS.

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A cardiac glucoside within vitroanti-HIV activity isolated fromElaeodendron croceum

Cited by 18 publications

References 6 publications

Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1/2-ERK1/2 signaling

Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1/2-ERK1/2 signaling

The efficacy and safety of nine South African medicinal plants in controlling Bacillus anthracis Sterne vaccine strain

Anti-HIV activity of southern African plants: Current developments, phytochemistry and future research

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