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Acacetin Blocks Kv1.3 Channels and Inhibits Human T Cell Activation
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TLDR
In this paper, a patch-clamp was applied to record the Kv1.3 and KCa currents in human T cells; Western blot was used to detect Kv 1.3 expression as well as NFAT1 and NF-κB activity; Fluo-4, CCK-8 and an ELISA kit were used to measure Ca2+ influx, proliferation, and IL 2 secretion, respectively.Abstract:
Backgrounds/Aims: Acacetin, a natural flavonoid compound, has been proven to exert antiinflammatory and immunomodulatory effects. Kv1.3 channels, highly expressed in human T cells, are attractive therapeutic targets to treat inflammatory and immunological disorders. The present study was designed to characterize the inhibition of Kv1.3 channels by Acacetin in human T cells and examine its role in T cell activation. Methods: Whole-cell patch-clamp was applied to record the Kv1.3 and KCa currents in human T cells; Western blot was used to detect Kv1.3 expression as well as NFAT1 and NF-κB activity; Fluo-4, CCK-8 and an ELISA kit were used to measure Ca2+ influx, proliferation, and IL-2 secretion, respectively. Results: Acacetin decreased the Kv1.3 current, accelerated the decay rate and negatively shifted the steadystate inactivation curves in a concentration-dependent manner. The IC50 values at +40 mV for peak and the current at end of pulse were 21.09 ± 2.75 and 3.63 ± 0.25 μmol/L, respectively. Treatment with Acacetin for 24 h significantly inhibited Kv1.3 protein expression. Additionally, paralleling Kv1.3 inhibition, Acacetin also inhibited Ca2+ influx, the Ca2+-activated transcription factors NFAT1, NF-κB p65/p50 activity, and proliferation as well as IL-2 production. Small interfering RNA against Kv1.3 reduced the inhibitory effect of Acacetin on IL-2 secretion. Conclusions: Acacetin blocks the Kv1.3 channel and inhibits human T cell activation. This action most likely contributes to its immunomodulatory and anti-inflammatory actions.read more
Citations
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Acacetin, a flavone with diverse therapeutic potential in cancer, inflammation, infections and other metabolic disorders.
TL;DR: Acacetin is a potent molecule reported for its strong anti-inflammatory and anti-cancer activity, however further scientific evidence is essential to validate its potency in disease models associated with inflammation and cancer.
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Voltage-Gated Potassium Channel Kv1.3 as a Target in Therapy of Cancer.
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Activation of transient receptor potential vanilloid 4 involves in hypoxia/reoxygenation injury in cardiomyocytes.
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Acacetin—A simple flavone exhibiting diverse pharmacological activities
Ruchi Badoni Semwal,Deepak Kumar Semwal,Deepak Kumar Semwal,Sandra Combrinck,Jeanne Trill,Simon Gibbons,Alvaro M. Viljoen +6 more
TL;DR: A comprehensive overview of the potential therapeutic applications of acacetin was prepared after collating selected peer-reviewed papers, accessed from online scientific databases, specifically PubMed, Web of Science and Scopus.
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