Exp Mol Med.  2009 Aug;41(8):538-547. 10.3858/emm.2009.41.8.059.

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

• Xi S
• Zhou G
• Zhang X
• Zhang W
• Cai L
• Zhao C

• KMID: 1119319
• DOI: http://doi.org/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 (ICa2+-L) and transient outward K+ channel current (Ito). 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 ICa2+-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 ICa2+-L in cardiac cells and decreasing CTGF expression.

Keyword

araloside; calcium channels, L-type; cardiomyopathies; connective tissue growth factor; diabetes mellitus; heart; hemodynamics; myocardium

MeSH Terms

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