Inhibition of key enzymes linked to type 2 diabetes by compounds isolated from <i>Aframomum melegueta</i> fruit

<p><b>Context:</b> The use of <i>Aframomum melegueta</i> K. Schum. (Zingiberaceae) fruit for treatment of diabetes has recently been established in Nigeria. However, compounds responsible for the antidiabetic action have not been identified.</p> <p><b>Objective:</b> The present study carried out the bioassay-guided isolation of possible bioactive compounds responsible for the antidiabetic action of <i>A. melegueta</i> fruit.</p> <p><b>Materials and methods:</b> The <i>A. melegueta</i> fruit was sequentially extracted using ethyl acetate (EtOAc), ethanol and water, and the most active extract (EtOAc) was subjected to column chromatography on a silica gel column using solvent gradient systems of hexane (HEX):EtOAc and EtOAc:MeOH and the isolation of compounds was guided by α-glycosidase and α-amylase inhibitory activities at various concentrations (30–240 μg/mL).</p> <p><b>Results:</b> According to the results, 3 arylalkanes, 6-paradol (<b>1</b>), 6-shogaol (<b>2</b>) and 6-gingerol (<b>3</b>) and a pentacyclic triterpene, oleanolic acid (<b>4</b>) were isolated from <i>A. melegueta</i> fruit. All the compounds exhibited inhibitory effects against α-amylase and α-glucosidase. 6-Gingerol (<b>3</b>) and oleanolic acid (<b>4</b>) showed higher inhibitory activity against α-amylase (IC₅₀: 6-gingerol: 81.78 ± 7.79 μM; oleanolic acid: 91.72 ± 1.63 μM) and α-glucosidase (IC₅₀: 6-gingerol: 21.55 ± 0.45 μM; oleanolic acid: 17.35 ± 0.88 μM) compared to the standard drug, acarbose and other isolated compounds. The kinetics of the enzyme action of the compounds showed a noncompetitive mode of inhibition.</p> <p><b>Conclusion:</b> The data of this study suggest that the 6-gingerol (<b>3</b>) and oleanolic acid (<b>4</b>) showed higher α-amylase and α-glucosidase inhibitory action and therefore could be responsible for the antidiabetic activity of <i>A. melegueta</i> fruit.</p

Visualization 1: OCT intensity and phase fluctuations correlated with activity-dependent neuronal calcium dynamics in the Drosophila CNS [Invited]

revised version of supplemental video for Figure 6 Originally published in Biomedical Optics Express on 01 February 2017 (boe-8-2-726

Visualization 1: OCT intensity and phase fluctuations correlated with activity-dependent neuronal calcium dynamics in the Drosophila CNS [Invited]

revised version of supplemental video for Figure 6 Originally published in Biomedical Optics Express on 01 February 2017 (boe-8-2-726

EPEC genes repressed 2-fold or more by Ler at mid-log phase (OD₆₀₀ = 0.4).

<p>Fold repression shows expression in <i>ler</i>⁻/<i>ler</i>⁺ cells. MGE, mobile genetic element; IE, integrative element; pMAR2, plasmid. For each gene reported, <i>t</i>-test P-value was less than 0.05.</p

Growth phase dependent Ler regulation of the EPEC <i>LEE1</i> operon.

<p>While the other major operons of the EPEC LEE are regulated by Ler in a similar manner in both mid and late-log phase cultures, the <i>LEE1</i> operon (<i>ler</i> –<i>escU</i>) was strongly activated by Ler only in late log phase cultures. The <i>LEE1</i> operon and flanking genes are shown as block arrows and are coloured according to the fold activation seen in <i>ler</i>⁺ cells. Fold activation values are not shown for the <i>ler</i> gene as this is partly deleted in <i>ler</i>⁻ cells. The intergenic region between <i>ler</i> and <i>espG</i> has been contracted for clarity.</p

Bacterial strains used or constructed in this study.

<p>Bacterial strains used or constructed in this study.</p

EHEC genes activated 2-fold or more by Ler at late-log phase (OD₆₀₀ = 1.1).

<p>Fold activation shows expression in <i>ler</i>⁻⁺/<i>ler</i>⁻ cells. ±IE1b, directly adjacent to IE1b. For each gene reported, <i>t</i>-test P-value was less than 0.05. MGE, mobile genetic element; pO157, plasmid; PP, prophage; OI#, O-island number. For each gene reported, t-test P-value was less than 0.05.</p

EPEC genes activated 2-fold or more by Ler at mid-log phase (OD₆₀₀ = 0.4).

<p>Fold activation shows expression in <i>ler</i>⁻⁺/<i>ler</i>⁻ cells. MGE, mobile genetic element; PP, prophage; IE, integrative element; LEE, locus of enterocyte effacement; ±LEE, directly adjacent to the LEE; pMAR2, plasmid. For each gene reported, <i>t</i>-test P-value was less than 0.05.</p

Plasmids used or constructed in this study.

<p>Plasmids used or constructed in this study.</p

EPEC genes repressed 2-fold or more by Ler at late-log phase (OD₆₀₀ = 0.9).

<p>Fold repression shows expression in <i>ler</i>⁻/<i>ler</i>⁺ cells. ±IE1b, directly adjacent to IE1b. For each gene reported, <i>t</i>-test P-value was less than 0.05.</p