MECHANISMS UNDERLYING ACTION OF XINMAILONG INJECTION, A TRADITIONAL CHINESE MEDICINE IN CARDIAC FUNCTION IMPROVEMENT

Background: As a bioactive composite extracted from American cockroach, Xinmailong injection (XML) is used for the treatment of congestive heart failure (CHF) in China. Clinical data has provided evidence that XML has positive inotropic properties. The objective of this study was to assess the mechanisms involved in the therapeutical effect of XML on CHF. Materials and Methods: The effects of XML on the cardiac function in isolated rat heart were measured. A Ca2+ imaging technology was used in rat cardiomyocytes (H9c2 cells) to reveal the role of XML on Ca2+ channels. Meanwhile, the effects of XML on the activities of Na+/K+ ATPase and sodium/calcium exchanger were measured. In addition, the level of reactive oxygen species and the protein expressions for the superoxide dismutase and hemeoxygenase were determined in the cardiomyocytes. Results: The results showed that XML increased the electrical impulse-induced [Ca2+]i in H9c2 cells, which was dependant on extracellular Ca2+ and was abolished by ML218-HCl (a T-type Ca2+channels antagonist) but not nimodipine (a L-type Ca2+channels antagonist). Ouabain, a Na+/K+-ATPase inhibitor, increased the electrical impulse-induced [Ca2+]i, which was significantly inhibited by XML. Moreover, XML markedly inhibited the Na+/K+ ATPase activity in H9c2 cells. In addition, XML notably reduced the production of reactive oxygen species and enhanced the protein expressions of antioxidant enzymes including superoxide dismutase 1, superoxide dismutase 2 and hemeoxygenase 1 in H9c2 cell. Conclusion: Our findings pave the ways to the better understandings of the therapeutic effects of XML on cardiovascular system

VASOCONSTRICTIVE EFFECT OF XINMAILONG IN RAT AORTA

Background: Cockroach has been utilized traditionally in China for the therapy of cardiovascular disorders, such as heart failure. The present study was aimed to assess the vasoconstrictive effect of Xinmailong Injection (XML), a bioactive composite from American cockroach. Methodology: The isometric tensions of rat aortic rings were measured after acutely treated with XML. Meanwhile, the systemic blood pressures (SBPs) were recorded and the levels of the endothelium-derived cytokines in blood samples were detected after rats were administered with XML for 3 days. Protein expression for the L-type Ca2+ channels (Cav1.2) was also determined in rat thoracic aorta. Results: XML induced vasoconstrictions in rat aortic rings with or without endothelium. In addition, the vasoconstrictions due to extracellular Ca2+ influx and intracellular Ca2+ release were also elevated by XML. After treatment with XML for 3 days, the levels of prostacyclin (PGI2) were markedly elevated whereas the levels of nitric oxide (NO) and endothelin-1 (ET-1) were not significantly changed in rats. Furthermore, expression of the Cav1.2 protein was significantly enhanced in aorta but the SBPs of rats were not influenced. Conclusion: XML plays an important role in regulating vascular tone. The increases of the extracellular Ca2+ influx and the intracellular Ca2+ release may contribute to the vasoconstriction induced by XML. Our findings pave the ways to better understand the therapeutic effects of XML on cardiovascular system