scholarly journals Anti-HIV Activity of Cucurbitacin-D against Cigarette Smoke Condensate-Induced HIV Replication in the U1 Macrophages

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1004
Author(s):  
Sunitha Kodidela ◽  
Namita Sinha ◽  
Asit Kumar ◽  
Santosh Kumar

Chemodietary agents are emerging as promising adjuvant therapies in treating various disease conditions. However, there are no adjuvant therapies available to minimize the neurotoxicity of currently existing antiretroviral drugs (ARVs). In this study, we investigated the anti-HIV effect of a chemodietary agent, Cucurbitacin-D (Cur-D), in HIV-infected macrophages using an in-vitro blood–brain barrier (BBB) model. Since tobacco smoking is prevalent in the HIV population, and it exacerbates HIV replication, we also tested the effect of Cur-D against cigarette smoke condensate (CSC)-induced HIV replication. Our results showed that Cur-D treatment reduces the viral load in a dose-dependent (0–1 µM) manner without causing significant toxicity at <1 µM concentration. Further, a daily dose of Cur-D (0.1 µM) not only reduced p24 in control conditions, but also reduced CSC (10 µg/mL)-induced p24 in U1 cells. Similarly, Cur-D (single dose of 0.4 µM) significantly reduced the CSC (single dose of 40 µg/mL)-induced HIV replication across the BBB model. In addition, treatment with Cur-D reduced the level of pro-inflammatory cytokine IL-1β. Therefore, Cur-D, as an adjuvant therapy, may be used not only to suppress HIV in the brain, but also to reduce the CNS toxicity of currently existing ARVs.

2015 ◽  
Vol 87 (2) ◽  
pp. 997-1005 ◽  
Author(s):  
Jinqiang Hu ◽  
Tao Wei ◽  
Siwen Sun ◽  
Aijing Zhao ◽  
Chunping Xu

The aim of the study was to investigate the effect of cigarette smoke on the production and characterization of exopolysaccharides (EPSs) produced by Bifidobacterium. Cigarettes of Shanhua brand (nicotine: 1.1 mg, tar: 11 mg) were utilized to prepare a cigarette smoke condensate (CSC). The standard strain of Bifidobacterium animalis was cultured in MRS media under anaerobic addition of CSC. The results showed that CSC significantly decreased the growth of B. animalis as well as EPSs and acetic acid production. Furthermore, two EPSs fractions (Fr-I and Fr-II) were isolated and purified for chemical and molecular determination. By comparison with control, CSC was found to be of great impact on EPSs carbohydrate composition. The molecular weight mass of Fr-I changed from 3.33×105 g/mol (without CSC) to 2.99×105 (with CSC). In conclusion, in vitro studies revealed that CSC was directly able to affect the production of metabolites for B. animalis, which could be an essential factor in certain pathological disorders.


1994 ◽  
Vol 266 (4) ◽  
pp. L382-L388 ◽  
Author(s):  
A. J. Ghio ◽  
J. Stonehuerner ◽  
D. R. Quigley

Deposition of pigmented matter in the lower respiratory tract correlates with the extent of emphysema in smokers as well as with free radical generation and iron accumulation. Pulmonary emphysema is postulated to be mediated by free radical generation which is either directly or indirectly associated with cigarette smoke exposure. The hypothesis was tested that 1) incomplete combustion of tobacco yields humic-like substances (HLS) which 2) deposit in the lung as pigmented particulates, 3) complex iron cations in vitro and in vivo, and 4) have a capacity to catalyze oxidant formation. HLS, isolated by alkali extraction of cigarette smoke condensate (CSC) (Tobacco Health Research Institute, University of Kentucky), demonstrated a high carbon and low carboxylate content on elemental and functional group analyses, respectively, compared with values for HLS sequestered from soils. The HLS isolated from CSC had a capacity to complex iron in vitro and accumulated the metal in vivo after intratracheal instillation in an animal model. Both HLS and its iron complex generated free radicals, and some portion of this oxidant generation was metal dependent. Lung tissue collected at autopsy from smokers contained HLS with an infrared spectrum almost identical to that of the material isolated from CSC. Associations between particulate deposition, metal accumulation, and free radical generation suggest a possible role of HLS in the induction of lung disease following cigarette exposure.


Oncogene ◽  
2004 ◽  
Vol 23 (35) ◽  
pp. 5880-5889 ◽  
Author(s):  
Satya Narayan ◽  
Aruna S Jaiswal ◽  
Diana Kang ◽  
Pratima Srivastava ◽  
Gokul M Das ◽  
...  

1985 ◽  
Vol 157 (2-3) ◽  
pp. 169-180 ◽  
Author(s):  
Margareta Curvall ◽  
Tommy Jansson ◽  
Bertil Pettersson ◽  
Annica Hedin ◽  
Curt R. Enzell

2004 ◽  
Vol 58 (2) ◽  
pp. 90-94 ◽  
Author(s):  
Pascale Nguyen Van Binh ◽  
Dong Zhou ◽  
Françoise Baudouin ◽  
Chantal Martin ◽  
Martine Radionoff ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Tong-Cui Ma ◽  
Run-Hong Zhou ◽  
Xu Wang ◽  
Jie-Liang Li ◽  
Ming Sang ◽  
...  

Abstract The Bowman-Birk inhibitor (BBI), a soybean-derived protease inhibitor, is known to have anti-inflammatory effect in both in vitro and in vivo systems. Macrophages play a key role in inflammation and immune activation, which is implicated in HIV disease progression. Here, we investigated the effect of BBI on HIV infection of peripheral blood monocyte-derived macrophages. We demonstrated that BBI could potently inhibit HIV replication in macrophages without cytotoxicity. Investigation of the mechanism(s) of BBI action on HIV showed that BBI induced the expression of IFN-β and multiple IFN stimulated genes (ISGs), including Myxovirus resistance protein 2 (Mx2), 2′,5′-oligoadenylate synthetase (OAS-1), Virus inhibitory protein (viperin), ISG15 and ISG56. BBI treatment of macrophages also increased the expression of several known HIV restriction factors, including APOBEC3F, APOBEC3G and tetherin. Furthermore, BBI enhanced the phosphorylation of IRF3, a key regulator of IFN-β. The inhibition of IFN-β pathway by the neutralization antibody to type I IFN receptor (Anti-IFNAR) abolished BBI-mediated induction of the anti-HIV factors and inhibition of HIV in macrophages. These findings that BBI could activate IFN-β-mediated signaling pathway, initialize the intracellular innate immunity in macrophages and potently inhibit HIV at multiple steps of viral replication cycle indicate the necessity to further investigate BBI as an alternative and cost-effective anti-HIV natural product.


2014 ◽  
Vol 59 (1) ◽  
pp. 397-406 ◽  
Author(s):  
Tomokazu Yoshinaga ◽  
Masanori Kobayashi ◽  
Takahiro Seki ◽  
Shigeru Miki ◽  
Chiaki Wakasa-Morimoto ◽  
...  

ABSTRACTGSK1265744 is a new HIV integrase strand transfer inhibitor (INSTI) engineered to deliver efficient antiviral activity with a once-daily, low-milligram dose that does not require a pharmacokinetic booster. Thein vitroantiviral profile and mechanism of action of GSK1265744 were established through integrase enzyme assays, resistance passage experiments, and cellular assays with site-directed molecular (SDM) HIV clones resistant to other classes of anti-HIV-1 agents and earlier INSTIs. GSK1265744 inhibited HIV replication with low or subnanomolar efficacy and with a selectivity index of at least 22,000 under the same culture conditions. The protein-adjusted half-maximal inhibitory concentration (PA-EC50) extrapolated to 100% human serum was 102 nM. When the virus was passaged in the presence of GSK1265744, highly resistant mutants with more than a 10-fold change (FC) in EC50relative to that of the wild-type were not observed for up to 112 days of culture. GSK1265744 demonstrated activity against SDM clones containing the raltegravir (RAL)-resistant Y143R, Q148K, N155H, and G140S/Q148H signature variants (FC less than 6.1), while these mutants had a high FC in the EC50for RAL (11 to >130). Either additive or synergistic effects were observed when GSK1265744 was tested in combination with representative anti-HIV agents, and no antagonistic effects were seen. These findings demonstrate that, similar to dolutegravir, GSK1265744 is differentiated as a new INSTI, having a markedly distinct resistance profile compared with earlier INSTIs, RAL, and elvitegravir (EVG). The collective data set supports further clinical development of GSK1265744.


1986 ◽  
Vol 169 (3) ◽  
pp. 129-139 ◽  
Author(s):  
Tommy Jansson ◽  
Margareta Curvall ◽  
Annica Hedin ◽  
Curt R. Enzell

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