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Keywords:

  • cultured myocardial cell;
  • positive chronotropic effect;
  • spontaneous beating;
  • Zanthoxylum bungeanum

Abstract

In the course of our studies on naturally occurring cardioactive agents, we investigated the effects of water and methanol extracts of a Chinese crude drug “Huajiao” the dried fruit of Zanthoxylum bungeanum, on the spontaneous beating rate (BR) of embryonic mouse myocardial cell sheets in culture. Both extracts significantly increased the BR. Through bioassay directed fractionation of the extracts, hydroxy-β-sanshool (1b), xanthoxylin (2) and two quercetin glycosides, hyperin (4) and quercitrin (6), were found to increase the BR in a standard medium (2.1 mM Ca2+). In a low Ca2+ medium (0.5 mM Ca2+), these compounds suppressed the decrease of BR, which was induced by low Ca2+. Of 16 flavonoids related in structure with hyperin (4) and quercitrin (6), quercetin, isoquercitrin, rutin, myricetin and myricitrin also increased the BR in the standard medium, while kaempferol and luteorin decreased the BR in the standard medium. When compared with control, hydroxy-β-sanshool (1b) and xanthoxylin (2) stimulated 13–15 fold calcium uptake of the cultured myocardial cells, which might have caused the positive chronotropic effect. Hyperin (4) and quercitrin (6) did not affect calcium uptake of the myocardial cells, Na+–K+ ATPase activity or Ca2+-ATPase activity of sarcoplasmic reticulum.