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Modulation of Kv7 Channel Currents by Echinocystic Acid.
Geng, DanDan; Li, Yaning; Zheng, Rong; Wang, Runmeng; Yang, Bo; Zhang, Huaxing; Zhang, Yang; Zhang, Fan.
Afiliación
  • Geng D; The Key Laboratory of Neural and Vascular Biology, Ministry of Education (D.D.G., Y.L., R.Z., B.Y., F.Z.), Department of Biochemistry and Molecular Biology (D.D.G., Y.L., R.Z., B.Y., F.Z.), The Core Facilities and Centers (H.Z.), and School of Pharmacy (Y.Z.), Hebei Medical University, Shijiazhuang,
  • Li Y; The Key Laboratory of Neural and Vascular Biology, Ministry of Education (D.D.G., Y.L., R.Z., B.Y., F.Z.), Department of Biochemistry and Molecular Biology (D.D.G., Y.L., R.Z., B.Y., F.Z.), The Core Facilities and Centers (H.Z.), and School of Pharmacy (Y.Z.), Hebei Medical University, Shijiazhuang,
  • Zheng R; The Key Laboratory of Neural and Vascular Biology, Ministry of Education (D.D.G., Y.L., R.Z., B.Y., F.Z.), Department of Biochemistry and Molecular Biology (D.D.G., Y.L., R.Z., B.Y., F.Z.), The Core Facilities and Centers (H.Z.), and School of Pharmacy (Y.Z.), Hebei Medical University, Shijiazhuang,
  • Wang R; The Key Laboratory of Neural and Vascular Biology, Ministry of Education (D.D.G., Y.L., R.Z., B.Y., F.Z.), Department of Biochemistry and Molecular Biology (D.D.G., Y.L., R.Z., B.Y., F.Z.), The Core Facilities and Centers (H.Z.), and School of Pharmacy (Y.Z.), Hebei Medical University, Shijiazhuang,
  • Yang B; The Key Laboratory of Neural and Vascular Biology, Ministry of Education (D.D.G., Y.L., R.Z., B.Y., F.Z.), Department of Biochemistry and Molecular Biology (D.D.G., Y.L., R.Z., B.Y., F.Z.), The Core Facilities and Centers (H.Z.), and School of Pharmacy (Y.Z.), Hebei Medical University, Shijiazhuang,
  • Zhang H; The Key Laboratory of Neural and Vascular Biology, Ministry of Education (D.D.G., Y.L., R.Z., B.Y., F.Z.), Department of Biochemistry and Molecular Biology (D.D.G., Y.L., R.Z., B.Y., F.Z.), The Core Facilities and Centers (H.Z.), and School of Pharmacy (Y.Z.), Hebei Medical University, Shijiazhuang,
  • Zhang Y; The Key Laboratory of Neural and Vascular Biology, Ministry of Education (D.D.G., Y.L., R.Z., B.Y., F.Z.), Department of Biochemistry and Molecular Biology (D.D.G., Y.L., R.Z., B.Y., F.Z.), The Core Facilities and Centers (H.Z.), and School of Pharmacy (Y.Z.), Hebei Medical University, Shijiazhuang,
  • Zhang F; The Key Laboratory of Neural and Vascular Biology, Ministry of Education (D.D.G., Y.L., R.Z., B.Y., F.Z.), Department of Biochemistry and Molecular Biology (D.D.G., Y.L., R.Z., B.Y., F.Z.), The Core Facilities and Centers (H.Z.), and School of Pharmacy (Y.Z.), Hebei Medical University, Shijiazhuang,
Mol Pharmacol ; 104(2): 42-50, 2023 08.
Article en En | MEDLINE | ID: mdl-37280100
Modulation of KCNQ-encoded voltage-gated potassium Kv7/M channel function represents an attractive strategy to treat neuronal excitability disorders such as epilepsy, pain, and depression. The Kv7 channel group includes five subfamily members (Kv7.1-Kv7.5). Pentacyclic triterpenes display extensive pharmacological activities including antitumor, anti-inflammatory, and antidepression effects. In this study, we investigated the effects of pentacyclic triterpenes on Kv7 channels. Our results show that echinocystic acid, ursonic acid, oleanonic acid, demethylzeylasteral, corosolic acid, betulinaldehyde, acetylursolic acid, and α-boswellic acid gradually exert decreasing degrees of Kv7.2/Kv7.3 channel current inhibition. Echinocystic acid was the most potent inhibitor, with a half-maximal inhibitory concentration (IC50) of 2.5 µM. It significantly shifted the voltage-dependent activation curve in a positive direction and slowed the time constant of activation for Kv7.2/Kv7.3 channel currents. Furthermore, echinocystic acid nonselectively inhibited Kv7.1-Kv7.5 channels. Taken together, our findings indicate that echinocystic acid is a novel and potent inhibitor that could be used as a tool to further understand the pharmacological functions of neuronal Kv7 channels. SIGNIFICANCE STATEMENT: Pentacyclic triterpenes reportedly have multiple potential therapeutic uses such as anticancer, anti-inflammatory, antioxidant, and antidepression effects. In the present study, we show that echinocystic acid, ursonic acid, oleanonic acid, and demethylzeylasteral inhibit Kv7.2/Kv7.3 channels to varying degrees. Of these, echinocystic acid was the most potent Kv7.2/Kv7.3 current inhibitor and inhibited Kv7.1-Kv7.5 currents in a nonselective manner.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ácido Oleanólico / Canales de Potasio con Entrada de Voltaje Idioma: En Revista: Mol Pharmacol Año: 2023 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ácido Oleanólico / Canales de Potasio con Entrada de Voltaje Idioma: En Revista: Mol Pharmacol Año: 2023 Tipo del documento: Article