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The inhibitory effect of shakuyakukanzoto on K+ current in H9c2 cells.

Abstract
Shakuyakukanzoto (shao-yao-gan-cao-tang) is a commonly used Chinese traditional herbal medicine for the treatment of acute pain with muscle cramp. However, its mechanism of action is unclear. We previously reported that a low concentration of Kanzo (licorice) and isoliquiritigenin, a component of licorice, inhibited the potassium (K(+)) current in H9c2 cells. Therefore, in the present study, we examined the effects of Shakuyakukanzoto, Shakuyaku or Kanzo on the K(+) current (IKur) in H9c2 cells. Shakuyakukanzoto inhibited IKur in a concentration-dependent manner. The half-maximal concentration of Shakuyakukanzoto was approximately 1.3 mg/mL and the Hill coefficient was 1.2. The order of potency of inhibiting IKur was Kanzo>Shakuyakukanzoto>Shakuyaku. Glycyrrhizin, a major component of licorice, had no inhibitory effect on IKur. A small interfering RNA experiment indicated that IKur was most likely to be Kv2.1 in H9c2 cells. Our results suggest that Shakuyakukanzoto may normalize intracellular and extracellular K(+) balance by inhibiting IKur and reducing K(+) efflux, while the Na(+)-K(+) pump promotes K(+) influx into myofibers. Consequently, excess K(+) may be reduced from external space of myofibers. This may be a part of the Shakuyakukanzoto mechanism for improving muscle pain.
AuthorsAzusa Suganami, Kazuho Sakamoto, Tomoyuki Ono, Hirotake Watanabe, Nahoko Hijioka, Masahiro Murakawa, Junko Kimura
JournalFukushima journal of medical science (Fukushima J Med Sci) Vol. 60 Issue 1 Pg. 22-30 ( 2014) ISSN: 2185-4610 [Electronic] Japan
PMID24670676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drug Combinations
  • Drugs, Chinese Herbal
  • Kcnb1 protein, rat
  • RNA, Small Interfering
  • Shab Potassium Channels
  • shakuyaku-kanzoh-toh
  • Glycyrrhizic Acid
  • Potassium
Topics
  • Animals
  • Cell Line
  • Drug Combinations
  • Drugs, Chinese Herbal (pharmacology)
  • Glycyrrhiza (chemistry)
  • Glycyrrhizic Acid (pharmacology)
  • Humans
  • Ion Transport (drug effects)
  • Muscle Cramp (drug therapy, metabolism)
  • Muscle Fibers, Skeletal (drug effects, metabolism)
  • Paeonia
  • Potassium (metabolism)
  • RNA, Small Interfering (genetics)
  • Rats
  • Shab Potassium Channels (antagonists & inhibitors, genetics, metabolism)

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