Protective effect of total aralosides of Aralia elata (Miq) Seem (TASAES) against diabetic cardiomyopathy in rats during the early stage, and possible mechanisms

Exp Mol Med. 2009 Aug 31;41(8):538-47. doi: 10.3858/emm.2009.41.8.059.

Abstract

Total aralosides of Aralia elata (Miq) Seem (TASAES) from Chinese traditional herb Longya Aralia chinensis L was found to improve cardiac function. The present study was to determine the protective effects of TASAES on diabetic cardiomyopathy, and the possible mechanisms. Therefore, a single dose of streptozotocin was used to induce diabetes in Wister rats. Diabetic rats were immediately treated with low, medium and high doses of TASAES at 4.9, 9.8 mg/kg and 19.6 mg/kg body weight by gavage, respectively, for eight weeks. Cardiac function was evaluated by in situ hemodynamic measurements, and patch clamp for the L-type Ca2+ channel current I(Ca(2+)-L) and transient outward K+ channel current (I(to)). Histopathological changes were observed under light and electron microscope. The expression of pro-fibrotic factor, connective tissue growth factor (CTGF) was monitored using immunohistochemistry staining. Compared with diabetic group, medium and high doses, but not low dose, of TASAES showed a significant protection against diabetes-induced cardiac dysfunction, shown by increased absolute value of left ventricular systolic pressure (LVSP) and maximum rates of pressure development (+/-dp/dt(max)), and enhanced amplitude of I(Ca(2+)-L) (P<0.05). Histological staining indicated a significant inhibition of diabetes-caused pathological changes and up-regulation of CTGF expression (P< 0.05). The results suggest that TASAES prevents diabetes-induced cardiac dysfunction and pathological damage through up-regulating I(Ca(2+)-L) in cardiac cells and decreasing CTGF expression.

MeSH terms

  • Animals
  • Aralia / chemistry*
  • Calcium Channels, L-Type / physiology
  • Cardiomyopathies / drug therapy*
  • Cardiomyopathies / etiology
  • Cardiomyopathies / physiopathology
  • Connective Tissue Growth Factor / metabolism
  • Diabetes Mellitus, Experimental / complications*
  • Drugs, Chinese Herbal / chemistry*
  • Heart / drug effects
  • Heart / physiopathology
  • Hemodynamics
  • Male
  • Myocardium / pathology
  • Oleanolic Acid* / analogs & derivatives
  • Oleanolic Acid* / therapeutic use
  • Patch-Clamp Techniques
  • Potassium Channels / physiology
  • Rats
  • Rats, Wistar
  • Saponins / therapeutic use*
  • Treatment Outcome

Substances

  • Calcium Channels, L-Type
  • Drugs, Chinese Herbal
  • Potassium Channels
  • Saponins
  • Connective Tissue Growth Factor
  • Oleanolic Acid