Chronic human immunodeficiency virus (HIV) infection, separately and in combination with highly active antiretroviral therapy (HAART) is closely associated with oxidative stress (OS). Most studies demonstrating redox imbalances in HIV-infected individuals have done so using conventional biochemical methodologies. The limited simultaneous detection of multiple OS markers within one sample is a major drawback of these methodologies and can be addressed through the use of metabonomics. HIV-metabonomic studies utilizing biofluids from HAART cohorts as the investigative source, are on the increase. Data from many of these studies identified metabolic markers indicative of HIV-induced OS, usually as an outcome of an untargeted metabonomics study. Untargeted studies cast a wide net for any and all detectable metabolites in complex mixtures. Given the prevalence of OS during HIV infection and antiviral treatment, it is perhaps not surprising that indicators of this malady would become evident during metabolite identification. At times, targeted studies for specific (non-OS) metabolites would also yield OS markers as an outcome. This review examines the findings of these studies by first providing the necessary background information on OS and the main ways in which free radicals/reactive oxygen species (ROS) produced during OS, cause biomolecular damage. This is followed by information on the biomarkers which come about as a result of free radical damage and the techniques used for assaying these stress indicators. The established links between elevated ROS and lowered antioxidants during HIV infection and the subsequent use of HAART is then presented followed by a review of the OS markers detected in HIV metabonomic studies to date. We identify gaps in HIV/HAART-associated OS research and finally suggest how these research gaps can be addressed through metabonomic analysis, specifically targeting the multiple markers of HIV-induced OS.

Global health, whether in developed or developing countries, is in need of robust systems diagnostics for major diseases, such as HIV/AIDS, impacting the world populations. Fourier transform Infrared (FTIR) spectroscopy of serum is a quick and reagent-free methodology with which to analyze metabolic alterations such as those caused by disease or treatment. In this study, Attenuated Total Reflectance Fourier-Transform (ATR-FTIR) Spectroscopy was investigated as a means of distinguishing HIV-infected treatment-experienced (HIV ^pos ART ^pos , n =39) and HIV-infected-treatment-naïve (HIV ^pos ART ^neg , n =16) subjects from uninfected control subjects ( n =30). Multivariate pattern recognition techniques, including partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA), successfully distinguished sample classes, while univariate approaches identified significant differences ( p 90%. Compared to uninfected controls, HIV ^pos ART ^pos and HIV ^pos ART ^neg subjects displayed significant differences in spectral regions linked to lipids/fatty acids (3010 cm ⁻¹ ), carbohydrates (1299 cm ⁻¹ ; 1498 cm ⁻¹ ), glucose (1035 cm ⁻¹ ), and proteins (1600 cm ⁻¹ ; 1652 cm ⁻¹ ). These are all molecules shown by conventional biochemical analysis to be affected by HIV/ART interference. The biofluid metabolomics approach applied here successfully differentiated global metabolic profiles of HIV-infected patients and uninfected controls and detected potential biomarkers for development into indicators of host response to treatment and/or disease progression. Our findings therefore contribute to ongoing efforts for capacity-building in global health for robust omics science and systems diagnostics towards major diseases impacting population health.

Bioassay-guided fractionation using different chromatographic and spectroscopic techniques in the analysis of the Red Sea soft coral Litophyton arboreum led to the isolation of nine compounds; sarcophytol M (1), alismol (2), 24-methylcholesta-5,24(28)-diene-3β-ol (3), 10-O-methyl alismoxide (4), alismoxide (5), (S)-chimyl alcohol (6), 7β-acetoxy-24-methylcholesta-5-24(28)-diene-3,19-diol (7), erythro-N-dodecanoyl-docosasphinga-(4E,8E)-dienine (8), and 24-methylcholesta-5,24 (28)-diene-3β,7β,19-triol (9). Some of the isolated compounds demonstrated potent cytotoxic- and/or cytostatic activity against HeLa and U937 cancer cell lines and inhibitory activity against HIV-1 protease (PR). Compound 7 was strongly cytotoxic against HeLa cells (CC₅₀ 4.3 ± 0.75 µM), with selectivity index of SI 8.1, which was confirmed by real time cell electronic sensing (RT-CES). Compounds 2, 7, and 8 showed strong inhibitory activity against HIV-1 PR at IC₅₀s of 7.20 ± 0.7, 4.85 ± 0.18, and 4.80 ± 0.92 µM respectively. In silico docking of most compounds presented comparable scores to that of acetyl pepstatin, a known HIV-1 PR inhibitor. Interestingly, compound 8 showed potent HIV-1 PR inhibitory activity in the absence of cytotoxicity against the cell lines used. In addition, compounds 2 and 5 demonstrated cytostatic action in HeLa cells, revealing potential use in virostatic cocktails. Taken together, data presented here suggest Litophyton arboreum to contain promising compounds for further investigation against the diseases mentioned.

Monitoring the progression of HIV infection to full-blown acquired immune deficiency syndrome (AIDS) and assessing responses to treatment will benefit greatly from the identification of novel biological markers especially since existing clinical indicators of disease are not infallible. Nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are powerful methodologies used in metabonomic analyses for an approximation of HIV-induced changes to the phenotype of an infected individual. Although early in its application to HIV/AIDS, (biofluid) metabonomics has already identified metabolic pathways influenced by both HIV and/or its treatment. To date, biofluid NMR and MS data show that the virus and highly active antiretroviral treatment (HAART) mainly influence carbohydrate and lipid metabolism, suggesting that infected individuals are susceptible to very specific metabolic complications. A number of well-defined biofluid metabonomic studies clearly distinguished HIV negative, positive and treatment experienced patient profiles from one another. While many of the virus or treatment affected metabolites have been identified, the metabonomics measurements were mostly qualitative. The identities of the molecules were not always validated neither were the statistical models used to distinguish between groups. Assigning particular metabolic changes to specific drug regimens using metabonomics also remains to be done. Studies exist where identified metabolites have been linked to various disease states suggesting great potential for the use of metabonomics in disease prognostics. This review therefore examines the field of metabonomics in the context of HIV/AIDS, comments on metabolites routinely detected as being affected by the pathogen or treatment, explains what existing data suggest and makes recommendations on future research.

Plants from the genus Ocimum are used as folk medicine for treating various diseases including inflammatory and immune-related diseases. Numerous reports have suggested plant extracts and their constituents as possible anti-inflammatory agents. Here, in vitro evidence of Ocimum labiatum’s immune-enhancing and antioxidant properties is presented for the first time. The anti-inflammatory effect of O. labiatum ethanolic extract and an isolated diterpenoid was determined using a cytometric bead array (CBA) technique. The effect on phytohemagglutinin (PHA)-induced nitric oxide (NO) production in peripheral blood mononuclear cells (PBMCs) was also assessed. A battery of antioxidant assays were used for detecting antioxidant activity while the anti-inflammatory mechanism was evaluated using an ELISA-based activator protein (AP-1) (c-Jun) assay. Cytotoxicity was determined on TZM-bl and PBMCs using a tetrazolium dye and confirmed by a novel label-free real-time assay. A 25 μg/mL non-cytotoxic concentration of O. labiatum extract significantly (p < 0.05) inhibited the production of pro-inflammatory cytokines; IL-2, IL-4, IL-6 and IL-17A. Except for the dual acting pro- or anti-inflammatory cytokine, IL-6, which was upregulated, a non-cytotoxic 50 μM concentration of the isolated labdane diterpenoid compound significantly (p < 0.05) decreased the production of all the pro-inflammatory cytokines. In the anti-inflammatory pathway studies, the compound also inhibited AP-1 significantly (p < 0.05) at 50 μM. The extract demonstrated strong, dose dependent antioxidant activity with IC50 values ranging from 13 ± 0.8 to 54.86 ± 1.28 μg/mL while the terpene had no antioxidant property. The extract and diterpenoid decreased the production of the inflammatory mediator NO, at non-cytotoxic concentrations. The CC50 of the extract in TZM-bl and PBMCs was 62.6 ± 0.6 and 30.1 ± 0.4 μg/mL while that of the compound was 112.6 ± 0.2 and 70 ± 0.4 μM respectively. The real time studies confirmed tetrazolium dye assessed viability and also detected a unique growth pattern for the plant materials compared to untreated cells. O. labiatum extract demonstrated promising anti-inflammatory and antioxidant properties while the terpenoid showed anti-inflammatory but no antioxidant activity. The anti-inflammatory mechanism of the terpene was a result of inhibition of AP-1. These data represents promising first steps towards the development of naturally derived anti-inflammation drugs.