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

研究成果: Article

摘要

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.

原文English
文章編號172414
期刊European Journal of Pharmacology
856
DOIs
出版狀態Published - 2019 八月 5

指紋

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

All Science Journal Classification (ASJC) codes

  • Pharmacology

引用此文

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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.",
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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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