Differential suppression of delayed-rectifier and inwardly rectifier K+ currents by a group of ent-kaurane-type diterpenoids from Croton tonkinensis, in microglial cells

Hung Tsung Hsiao, Yu Chi Lee, Yen Chin Liu, Ping Chung Kuo, Sheng Nan Wu

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Abstract

Croton is an extensive flowering plant genus in the spurge family, Euphorbiaceae. Three croton compounds with the common ent-kaurane skeleton were purified from Croton tonkinensis. By using patch-clamp recording technique, we thoroughly examined the effect of a group of croton compounds, croton-01 (ent-18-acetoxy-7α-hydroxykaur-16-en-15-one), croton-02 (ent-7α,14β-dihydroxykaur-16-en-15-one), and croton-03 (ent-1β-acetoxy-7α,14β-dihydroxykaur-16-en-15-one), on the membrane current in SM826 and BV2 microglial cells. Although neither voltage-gated Na+ nor Ca2+ currents were present in these cells, both delayed-rectifier K+ outward (IK(DR))and inwardly rectifying K+ currents (IK(IR))were readily detected. Croton-03 differentially caused inhibition of IK(DR) or IK(IR) in a concentration-dependent manner. According to a minimal scheme, the shortening of the time constant in either the IK(DR)-related block or IK(IR) caused by different concentrations of croton-03 was quantitatively estimated with a dissociation constant of 6.45 and 29.5 μM, respectively. In SM826 cells differentiated with β-amyloid, inhibitory action on these K+ currents remained unaltered. In ultraviolet C-irradiated cells, the magnitude of IK(IR) was still decreased by addition of croton-03. Therefore, our study suggests that these ent-kaurane diterpenoids ought to somehow act on the cellular mechanisms by which they influence the functional activities of microglial cells.

Original languageEnglish
Article number172414
JournalEuropean Journal of Pharmacology
Volume856
DOIs
Publication statusPublished - 2019 Aug 5

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Kaurane Diterpenes
Croton
Diterpenes
Euphorbiaceae
Euphorbia
Patch-Clamp Techniques
Amyloid
Skeleton

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

@article{7832cf0c5a9d45e4998a55d7286bb175,
title = "Differential suppression of delayed-rectifier and inwardly rectifier K+ currents by a group of ent-kaurane-type diterpenoids from Croton tonkinensis, in microglial cells",
abstract = "Croton is an extensive flowering plant genus in the spurge family, Euphorbiaceae. Three croton compounds with the common ent-kaurane skeleton were purified from Croton tonkinensis. By using patch-clamp recording technique, we thoroughly examined the effect of a group of croton compounds, croton-01 (ent-18-acetoxy-7α-hydroxykaur-16-en-15-one), croton-02 (ent-7α,14β-dihydroxykaur-16-en-15-one), and croton-03 (ent-1β-acetoxy-7α,14β-dihydroxykaur-16-en-15-one), on the membrane current in SM826 and BV2 microglial cells. Although neither voltage-gated Na+ nor Ca2+ currents were present in these cells, both delayed-rectifier K+ outward (IK(DR))and inwardly rectifying K+ currents (IK(IR))were readily detected. Croton-03 differentially caused inhibition of IK(DR) or IK(IR) in a concentration-dependent manner. According to a minimal scheme, the shortening of the time constant in either the IK(DR)-related block or IK(IR) caused by different concentrations of croton-03 was quantitatively estimated with a dissociation constant of 6.45 and 29.5 μM, respectively. In SM826 cells differentiated with β-amyloid, inhibitory action on these K+ currents remained unaltered. In ultraviolet C-irradiated cells, the magnitude of IK(IR) was still decreased by addition of croton-03. Therefore, our study suggests that these ent-kaurane diterpenoids ought to somehow act on the cellular mechanisms by which they influence the functional activities of microglial cells.",
author = "Hsiao, {Hung Tsung} and Lee, {Yu Chi} and Liu, {Yen Chin} and Kuo, {Ping Chung} and Wu, {Sheng Nan}",
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T1 - Differential suppression of delayed-rectifier and inwardly rectifier K+ currents by a group of ent-kaurane-type diterpenoids from Croton tonkinensis, in microglial cells

AU - Hsiao, Hung Tsung

AU - Lee, Yu Chi

AU - Liu, Yen Chin

AU - Kuo, Ping Chung

AU - Wu, Sheng Nan

PY - 2019/8/5

Y1 - 2019/8/5

N2 - Croton is an extensive flowering plant genus in the spurge family, Euphorbiaceae. Three croton compounds with the common ent-kaurane skeleton were purified from Croton tonkinensis. By using patch-clamp recording technique, we thoroughly examined the effect of a group of croton compounds, croton-01 (ent-18-acetoxy-7α-hydroxykaur-16-en-15-one), croton-02 (ent-7α,14β-dihydroxykaur-16-en-15-one), and croton-03 (ent-1β-acetoxy-7α,14β-dihydroxykaur-16-en-15-one), on the membrane current in SM826 and BV2 microglial cells. Although neither voltage-gated Na+ nor Ca2+ currents were present in these cells, both delayed-rectifier K+ outward (IK(DR))and inwardly rectifying K+ currents (IK(IR))were readily detected. Croton-03 differentially caused inhibition of IK(DR) or IK(IR) in a concentration-dependent manner. According to a minimal scheme, the shortening of the time constant in either the IK(DR)-related block or IK(IR) caused by different concentrations of croton-03 was quantitatively estimated with a dissociation constant of 6.45 and 29.5 μM, respectively. In SM826 cells differentiated with β-amyloid, inhibitory action on these K+ currents remained unaltered. In ultraviolet C-irradiated cells, the magnitude of IK(IR) was still decreased by addition of croton-03. Therefore, our study suggests that these ent-kaurane diterpenoids ought to somehow act on the cellular mechanisms by which they influence the functional activities of microglial cells.

AB - Croton is an extensive flowering plant genus in the spurge family, Euphorbiaceae. Three croton compounds with the common ent-kaurane skeleton were purified from Croton tonkinensis. By using patch-clamp recording technique, we thoroughly examined the effect of a group of croton compounds, croton-01 (ent-18-acetoxy-7α-hydroxykaur-16-en-15-one), croton-02 (ent-7α,14β-dihydroxykaur-16-en-15-one), and croton-03 (ent-1β-acetoxy-7α,14β-dihydroxykaur-16-en-15-one), on the membrane current in SM826 and BV2 microglial cells. Although neither voltage-gated Na+ nor Ca2+ currents were present in these cells, both delayed-rectifier K+ outward (IK(DR))and inwardly rectifying K+ currents (IK(IR))were readily detected. Croton-03 differentially caused inhibition of IK(DR) or IK(IR) in a concentration-dependent manner. According to a minimal scheme, the shortening of the time constant in either the IK(DR)-related block or IK(IR) caused by different concentrations of croton-03 was quantitatively estimated with a dissociation constant of 6.45 and 29.5 μM, respectively. In SM826 cells differentiated with β-amyloid, inhibitory action on these K+ currents remained unaltered. In ultraviolet C-irradiated cells, the magnitude of IK(IR) was still decreased by addition of croton-03. Therefore, our study suggests that these ent-kaurane diterpenoids ought to somehow act on the cellular mechanisms by which they influence the functional activities of microglial cells.

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