18β-Glycyrrhetinic acid potently inhibits Kv1.3 potassium channels and T cell activation in human Jurkat T cells.

Ethnopharmacological Relevance: Licorice has been extensively used in traditional medicines for treatment of many diseases, including inflammations and immunological disorders. Recent studies have shown that the anti-inflammatory and immunomodulation activities of licorice have been attributed to its active component, glycyrretinic acid (GA). GA consists of two isoforms, 18α- and 18β-. However, its mechanism remains poorly understood.

Aim Of The Study: We compared the effects of two isoforms on Kv1.3 channels in Jurkat T cells and further characterized the inhibition of Kv1.3 channels by 18β-GA in CHO cells. In addition, we examined the effects of 18β-GA on Kv1.3 gene expression, Ca(2+) influx, proliferation, as well as IL-2 production in Jurkat T cells.

Materials And Methods: Whole-cell patch-clamp technique was applied to record Kv1.3 currents in Jurkat T or CHO cells. Real-time PCR and Western blotting were used to detect gene expression. Fluo-4, CCK-8 kit and ELISA kit were used to measure Ca(2+) influx, proliferation, and IL-2 secretion in Jurkat T cells, respectively.

Results: Superfusion of 18β-GA (10-100 µM) blocked Kv1.3 currents in Jurkat T cells, while 18α-GA at the same concentration had no effect. The 18β-GA induced inhibition had a voltage- and concentration-dependent manner with an IC50 of 23.9±1.5 µM at +40 mV in CHO cells. Furthermore, 18β-GA significantly inhibited Kv1.3 gene expression. In addition, paralleling Kv1.3 inhibition, 18β-GA also inhibited Ca(2+) influx, proliferation as well as IL-2 production in Jurkat T cells.

Conclusion: 18β-GA blocks Kv1.3 channels, which probably involves its anti-inflammatory and immunomodulation effects.