Radical scavenging compounds from the aerial parts of Solenostemon monostachys briq (Lamiaceae)

Background: Solenostemon monostachys Briq. (Lamiaceae) is a weed widely used in ethno medicine to treat infections and inflammatory conditions but the active compounds are yet to be identified. This study isolated and identified the radical scavenging compounds from S. monostachys crude extract using diphenyl-1, 1-picryl hydrazyl (DPPH) to monitor the separation.Materials and Methods: The crude extract of the aerial parts of the plant was evaluated for antimicrobial activity using the agar diffusion test, anti-inflammatory test using carrageenan induced oedema of the rat paw and radical scavenging test using diphenyl-1, 1-picryl hydrazyl (DPPH). Repeated chromatographic separation of the ethyl acetate and n-butanol fractions on silica gel and Sephadex LH-20, monitored by DPPH bio-autographic assay resulted in the isolation of seven active compounds, which were identified using spectroscopic methods and comparison with literature data.Results: The ethyl acetate and n-butanol fractions were the most active fractions and contained apigenin, apigenin glucuronide, luteolin, caffeic acid, methyl caffeate, rosmarinic acid and methyl rosmarinate as the radical scavenging compounds with EC50 values of 26.67 ± 0.31, 185.89 ± 1.02, 5.35 ± 0.31, 3.92 ± 0.06, 13.41 ± 0.18, 4.99 ± 0.10, 5.97 ± 0.08 μg/ml respectively compared with 2.32 ± 0.08 μg/ml for quercetin as the reference standard.Conclusion: The isolated compounds are reported for the first time in this plant. The presence of the compounds in S. monostachys P. Beauv. (Briq.) (Lamiaceae) may provide justification for some of the ethnomedicinal uses of the plant in infections and inflammatory conditions.Keywords: Flavonoids, caffeic acid derivatives, radical scavenging ability, Lamiacea

RADICAL SCAVENGING COMPOUNDS FROM THE AERIAL PARTS OF SOLENOSTEMON MONOSTACHYS BRIQ (LAMIACEAE)

Background: Solenostemon monostachys Briq. (Lamiaceae) is a weed widely used in ethno-medicine to treat infections and inflammatory conditions but the active compounds are yet to be identified. This study isolated and identified the radical scavenging compounds from S. monostachys crude extract using diphenyl-1, 1-picryl hydrazyl (DPPH) to monitor the separation. Materials and Methods: The crude extract of the aerial parts of the plant was evaluated for antimicrobial activity using the agar diffusion test, anti-inflammatory test using carrageenan induced oedema of the rat paw and radical scavenging test using diphenyl-1, 1-picryl hydrazyl (DPPH). Repeated chromatographic separation of the ethyl acetate and n-butanol fractions on silica gel and Sephadex LH-20, monitored by DPPH bio-autographic assay resulted in the isolation of seven active compounds, which were identified using spectroscopic methods and comparison with literature data. Results: The ethyl acetate and n-butanol fractions were the most active fractions and contained apigenin, apigenin glucuronide, luteolin, caffeic acid, methyl caffeate, rosmarinic acid and methyl rosmarinate as the radical scavenging compounds with EC50 values of 26.67 ± 0.31, 185.89 ± 1.02, 5.35 ± 0.31, 3.92 ± 0.06, 13.41 ± 0.18, 4.99 ± 0.10, 5.97 ± 0.08 μg/ml respectively compared with 2.32 ± 0.08 μg/ml for quercetin as the reference standard. Conclusion: The isolated compounds are reported for the first time in this plant. The presence of the compounds in S. monostachys P. Beauv. (Briq.) (Lamiaceae) may provide justification for some of the ethnomedicinal uses of the plant in infections and inflammatory conditions

ISOLATION AND CHARACTERIZATION OF CHEMICAL CONSTITUENTS FROM Chrysophyllum albidum G. DON-HOLL. STEM-BARK EXTRACTS AND THEIR ANTIOXIDANT AND ANTIBACTERIAL PROPERTIES

Background: The plant, Chrysophyllum albidum is indigenous to Nigeria and its stem-bark has found relevance in folkloric medicine for infections and oxidative stress linked diseases medicaments. The study targets to isolate the chemical constituents accountable for the antioxidant and antibacterial actions of the plant stem-bark to substantiate some of its ethnomedicinal uses. Materials and Methods: Stem-bark extract of Chrysophyllum albidum was obtained from 80 % ethanol was partitioned in sequence with ethyl acetate (EtOAc) and n-butanol. The solvent fractions and isolated compounds were verified for antioxidant chattels utilizing 2-2-diphenyl-1-picrylhydrazyl. Antibacterial actions were also assessed by agency of agar-diffusion and broth micro dilution methods. EtOAc fraction was on many occasions chromatographed on silica and Sephadex LH-20 column to afford four compounds and their chemical structures were proven with the employment of NMR (1D and 2D) and MS. Results: Chromatographic fractionation of EtOAc fraction with the premier antioxidant and antimicrobial activities afforded stigmasterol (1), epicatechin (2), epigallocatechin (3) and procyanidin B5 (4). Procyanidin B5 isolated for the first time from Chrysophyllum genus proven the supreme antioxidant activity with IC50 values of 8.8 µM and 11.20 µM in DPPH and nitric oxide assays respectively and equally established the ultmost inhibitory activity against Escherichia coli (MIC 156.25 μg/mL), Staphylococcus aureus (MIC 156.25 μg/mL), Pseudomonas aeruginosa (MIC 625 μg/mL) and Bacillus subtilis (MIC 156.25 μg/mL). Conclusion: The antibacterial and antioxidant activities of epicatechin, epigallocatechin and procyanidin B5 isolated from Chrysophyllum albidum stem-bark substantiate the folkloric use

Screening of the Pan-African Natural Product Library Identifies Ixoratannin A-2 and Boldine as Novel HIV-1 Inhibitors

The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, combined with adverse effects and potential risks of resistance to existing antiretroviral therapies, emphasize the need to identify new HIV inhibitors. Here we performed a virtual screen of molecules from the pan-African Natural Product Library, the largest collection of medicinal plant-derived pure compounds on the African continent. We identified eight molecules with structural similarity to reported interactors of Vpu, an HIV-1 accessory protein with reported ion channel activity. Using in vitro HIV-1 replication assays with a CD4+ T cell line and peripheral blood mononuclear cells, we confirmed antiviral activity and minimal cytotoxicity for two compounds, ixoratannin A-2 and boldine. Notably, ixoratannin A-2 retained inhibitory activity against recombinant HIV-1 strains encoding patient-derived mutations that confer resistance to protease, non-nucleoside reverse transcriptase, or integrase inhibitors. Moreover, ixoratannin A-2 was less effective at inhibiting replication of HIV-1 lacking Vpu, supporting this protein as a possible direct or indirect target. In contrast, boldine was less effective against a protease inhibitor-resistant HIV-1 strain. Both ixoratannin A-2 and boldine also inhibited in vitro replication of hepatitis C virus (HCV). However, BIT-225, a previously-reported Vpu inhibitor, demonstrated antiviral activity but also cytotoxicity in HIV-1 and HCV replication assays. Our work identifies pure compounds derived from African plants with potential novel activities against viruses that disproportionately afflict resource-limited regions of the world

Replication of HIV-1_NL4-3, HIV-1_Δvpu, and drug-resistant HIV-1 strains in CEM-GXR cells.

<p>Data shown are at Day 4 in the presence of 0.1 μM of established ARVs, relative to the replication rate of each HIV-1 strain in the presence of 0.1% DMSO vehicle control. *, p < 0.004 vs. HIV-1_NL4-3 replication.</p

Effects of compounds on HCV replication.

<p><b>A,</b> Cell viability at 72 h post-infection in the presence of compounds at defined concentrations. Data are normalized to the percent of viable cells in a HCV-infected culture plus 0.1% DMSO. <b>B,</b> HCV replication at 72 h post-infection in the presence of compounds. Data are normalized to percent HCV-infected cells plus 0.1% DMSO.</p

Effects of p-ANAPL compounds on cell viability and <i>in vitro</i> HIV-1 replication.

<p><b>A,</b> CEM-GXR cell viability at Day 4 in the presence of p-ANAPL compounds at defined concentrations. Data are normalized to the percent of viable cells in an HIV-1_NL4-3-infected culture plus 0.1% DMSO. <b>B,</b> HIV-1 replication in CEM-GXR cells at Day 4 in the presence of compounds. Data are normalized to percent HIV-1_NL4-3-infected cells plus 0.1% DMSO. Dose-response plots of ixoratannin A-2 and boldine are highlighted with blue and green arrows, respectively. <b>C</b>, PBMC viability at Day 5 in the presence of p-ANAPL compounds. Data are normalized to the percent of viable cells in an uninfected culture plus 0.1% DMSO. <b>D</b>, HIV-1 replication in PBMCs at Day 12 in the presence of p-ANAPL compounds, as measured by p24^Gag levels in cell culture supernatants. Data are normalized to percent HIV-1_NL4-3-infected cells plus 0.1% DMSO.</p

Putative HIV-1 Vpu inhibitors identified from virtual screening of the p-ANAPL.

<p><b>A,</b> Structures of four molecules predicted to interact with the Vpu ion channel [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121099#pone.0121099.ref020" target="_blank">20</a>]. <b>B,</b> Alignment of four molecules. Chemical substituents that define a shared pharmacophore are highlighted. <b>C,</b> Eight p-ANAPL molecules containing aspects of the shared pharmacophore. For each compound, root mean square deviation (RMSD) values are shown in parentheses.</p

Effects of ixoratannin A-2 and boldine on replication of HIV-1_Δvpu and ARV-resistant HIV-1 strains in CEM-GXR cells.

<p>In all experiments, data are normalized to the replication rate of each HIV-1 strain plus 0.1% DMSO at Day 4. <b>A-B,</b> effects of ixoratannin A-2 (<b>A</b>) and boldine (<b>B</b>) on HIV-1_NL4-3 and HIV-1_Δvpu replication. <b>C-D,</b> effects of ixoratannin A-2 (<b>C</b>) and boldine (<b>D</b>) on replication of ARV-resistant HIV-1 strains.*, p < 0.008 vs. HIV-1_NL4-3 at the same concentration of ixoratannin A-2 or boldine. ǂ, p < 0.008 for strain HIV-1_PR+RT and HIV-1_INT vs. HIV-1_NL4-3 at same concentration of ixoratannin A-2.</p