High Capability of Pentagalloylglucose (PGG) in Inhibiting Multiple Types of Membrane Ionic Currents
Pentagalloyglucose (PGG, penta-<i>O</i>-galloyl-β-<span style="font-variant: small-caps;">d</span>-glucose; 1,2,3,4,6-pentagalloyl glucose), a pentagallic acid ester of glucose, is recognized to possess anti-bacterial, anti-oxidative and anti-neoplastic activities....
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/24/9369 |
| Summary: | Pentagalloyglucose (PGG, penta-<i>O</i>-galloyl-β-<span style="font-variant: small-caps;">d</span>-glucose; 1,2,3,4,6-pentagalloyl glucose), a pentagallic acid ester of glucose, is recognized to possess anti-bacterial, anti-oxidative and anti-neoplastic activities. However, to what extent PGG or other polyphenolic compounds can perturb the magnitude and/or gating of different types of plasmalemmal ionic currents remains largely uncertain. In pituitary tumor (GH<sub>3</sub>) cells, we found out that PGG was effective at suppressing the density of delayed-rectifier K<sup>+</sup> current (<i>I</i><sub>K(DR)</sub>) concentration-dependently. The addition of PGG could suppress the density of proton-activated Cl<sup>−</sup> current (<i>I</i><sub>PAC</sub>) observed in GH<sub>3</sub> cells. The IC<sub>50</sub> value required for the inhibitory action of PGG on <i>I</i><sub>K(DR)</sub> or <i>I</i><sub>PAC</sub> observed in GH<sub>3</sub> cells was estimated to be 3.6 or 12.2 μM, respectively, while PGG (10 μM) mildly inhibited the density of the <i>erg</i>-mediated K<sup>+</sup> current or voltage-gated Na<sup>+</sup> current. The presence of neither chlorotoxin, hesperetin, kaempferol, morin nor iberiotoxin had any effects on <i>I</i><sub>PAC</sub> density, whereas hydroxychloroquine or 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5yl)oxy] butanoic acid suppressed current density effectively. The application of PGG also led to a decrease in the area of voltage-dependent hysteresis of <i>I</i><sub>PAC</sub> elicited by long-lasting isosceles-triangular ramp voltage command, suggesting that hysteretic strength was lessened in its presence. In human cardiac myocytes, the exposure to PGG also resulted in a reduction of ramp-induced <i>I</i><sub>K(DR)</sub> density. Taken literally, PGG-perturbed adjustment of ionic currents could be direct and appears to be independent of its anti-oxidative property. |
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| ISSN: | 1661-6596 1422-0067 |