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.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Potassium/metabolism , Animals , Cell Line , Drug Combinations , Glycyrrhiza/chemistry , Glycyrrhizic Acid/pharmacology , Humans , Ion Transport/drug effects , Muscle Cramp/drug therapy , Muscle Cramp/metabolism , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/metabolism , Paeonia , RNA, Small Interfering/genetics , Rats , Shab Potassium Channels/antagonists & inhibitors , Shab Potassium Channels/genetics , Shab Potassium Channels/metabolismABSTRACT
We report on the anesthetic management of a 69-year-old female Jehovah's Witness undergoing cardiopulmonary bypass to replace the ascending aorta; the patient refused transfusion of stored autologous or allogeneic blood products for religious reasons. The strategy involved preoperative hematopoiesis with recombinant human erythropoietin and iron, intraoperative acute normovolemic hemodilution, the use of a cell-saver system, administration of high-dose tranexamic acid, controlled hypotension, avoidance of low body temperature, simplification of the surgery, and lower blood dilution during cardiopulmonary bypass.
Subject(s)
Aorta/surgery , Blood Transfusion, Autologous , Jehovah's Witnesses , Aged , Anesthesia, General , Angioplasty , Anticoagulants/therapeutic use , Antifibrinolytic Agents/therapeutic use , Blood Volume , Cardiopulmonary Bypass , Erythropoietin/therapeutic use , Female , Hematopoiesis/drug effects , Hemodilution , Heparin/therapeutic use , Humans , Hypotension, Controlled , Recombinant Proteins , Tranexamic Acid/therapeutic use , Treatment RefusalABSTRACT
The effect of isoliquiritigenin (ISL), a component of licorice, on the voltage-dependent, ultra-rapidly activating delayed-rectifier K(+) current (IKur) was examined in H9c2 cells, a cell-line derived from rat cardiac myoblasts. IKur was recorded using the whole-cell patch clamp method with a pipette solution containing 140 mM K(+). Depolarizing voltage pulses of 200-ms duration were given with 10-mV steps every 10 s from -40 mV holding potential. ISL inhibited IKur in a concentration-dependent manner. The median inhibitory concentration (IC(50)) of ISL was approximately 0.11 microM and the Hill coefficient was 0.71. Using CHO cells expressing Kv1.5 IKur channels, ISL also inhibited Kv1.5 IKur, but less potently than the IKur current in H9c2 cells. Furthermore, in H9c2 cells, the licorice extract itself inhibited IKur in a manner similar to ISL. We conclude that ISL, one component of licorice, is a potent inhibitor of K(+) channels, which specifically in H9c2 cells could be Kv2.1, and that this inhibition may be involved in various pharmacological effects of licorice.