Mechanisms of action of xinmailong, a Chinese medicine derived from periplaneta Americana, in treating heart failure

Abstract

Chronic heart failure is one of the commonest fatal diseases in the world. Much work has been carried out to reveal its complicated pathogenesis and develop effective therapy. Positive inotropic drugs are the major type of drugs used in the treatment of heart failure. Xinmailong is a medicine derived from the extract of Periplaneta Americana. It is marketed in Mainland China as a proprietary product for treating chronic heart failure. Although clinical studies have demonstrated the therapeutic effectiveness of Xinmailong, the mechanism by which it can cure heart failure is still largely unknown. In our study, the results of calcium imaging demonstrated that Xinmailong increased the intracellular calcium level in H9c2, a rat cardiomyoblast cell line, induced by electrical stimulation. Unlike KB-R7943, which is a sodium-calcium exchanger inhibitor, Xinmailong did not affect the basal intracellular calcium level in H9c2 in the absence of electrical stimulation. It, implied that Xinmailong did not work on sodium-calcium exchanger. Xinmailong had no effect of thapsigargin-induced calcium release from sarcoplasmic reticulum. The effect of Xinmailong on intracellular calcium level in H9c2 was not inhibited by nimodipine, which is a L-type calcium channel blocker. It indicated that Xinmailong did not interact with L-type calcium channels. Further study is required to find out how Xinmailong increases intracellular calcium in cardiomyocytes. Apart from the above results, our study also demonstrated that Xinmailong exerted cardioprotective effect by reducing intracellular reactive oxygen species. The mechanism may involve the increased expressions of antioxidant enzymes such as superoxide dismutase 1 and 2.