Long-Term Treatment with a Chinese Herbal Formula, Sheng-Mai-San, Improves Cardiac Contractile Function in Aged Rats: The Role of Ca²⁺Homeostasis

Abstract

A Chinese herbal formula Sheng-Mai-Yin (SMY), the liquid dosage form of Sheng-Mai-San, has been used clinically for treating heart failure, particularly in aged patients. To investigate the effect of SMY treatment on the contractile function of aged hearts, we first examined cardiac hemodynamics in aged rats. To define the mechanism involved in the enhancement of cardiac function, we investigated the effect of SMY treatment on Ca(2+) homeostasis in ventricular cardiomyocytes isolated from aged rats. Ca(2+) release was assessed by measurements of changes in cardiac Ca(2+) transients and Ca(2+) sparks, using laser scanning confocal microscopy. The functional status of Ca(2+)-release regulators, including L-type Ca(2+) channels, sarcoplasmic reticulum (SR) Ca(2+)-adenosine triphosphatase (ATPase), and ryanodine receptors (RyRs), was also assessed. The results indicated that SMY treatment (2 g/kg per day for 30 doses within 6 weeks, intragastically) significantly improved hemodynamic parameters in aged rats. SMY treatment markedly increased the amplitude and shortened the duration of Ca(2+) transients in aged cardiomyocytes, and reversed the age-related increase in frequency, decrease in amplitude, and changes in spatiotemporal properties of Ca(2+) sparks in cardiomyocytes. In addition, SMY treatment increased the L-type Ca(2+) current density, SR Ca(2+) content, and SR Ca(2+)-ATPase expression, and decreased the sensitivity of RyRs to Ca(2+), all of which are causally related to increases in the amplitude of Ca(2+) transients and the size of Ca(2+) sparks. In conclusion, the improvement in cardiac contractile function afforded by SMY treatment in aged rats is likely mediated by an increase in Ca(2+) release from the SR through L-type Ca(2+) current-activated RyRs.

Protective effect of Sheng-Mai Yin, a traditional Chinese preparation, against doxorubicin-induced cardiac toxicity in rats

“…Shengmai, as a traditional Chinese medicine, is usually used in China as a complementary treatment to western treatments that are recommended for acute heart failure, and also as a single treatment for chronic heart failure [ 26 ]. Previous studies have focused on the study of SMY on ischemic cardiomyopathy [ 27 , 28 ] or contractile function of aged hearts [ 17 ]. There are few reported studies about SMY on non-ischemic cardiomyopathy, such as DOX-induced cardiomyopathy and heart failure.…”

“…A voucher specimen of each species was also deposited at Tianjin University of Traditional Chinese Medicine. To prepare the SMY [ 17 ], the mixture of the three herbs were pulverized to coarse powder, macerated in 65 % (vol/vol, in H 2 O) ethanol (11.5 mL/g) for 24 h, and then extracted by percolation. The extracts were concentrated, followed by removing undissolved particulates by filtration.…”

Protective effect of Shenmai injection on knee articular cartilage of osteoarthritic rabbits and IL-1β-stimulated human chondrocytes

“…Shenmai injection (SMI) is widely used to clinically treat coronary heart disease, chronic pulmonary heart disease, viral myocarditis, heart and respiratory failure, cerebral infarction and malignant diseases (19)(20)(21)(22)(23)(24). In addition, the toxicity of SMI has been evaluated and it is generally considered to be safe to use (25,26).…”

Treatment of the cardiac hypertrophic response and heart failure with ginseng, ginsenosides, and ginseng-related products

“…The clinical aspects of Shengmai are discussed below although this agent has been shown to reduce cardiomyopathy produced by adriamyacin administration to rats (You et al 2006). Moreover, treatment of aged rats for six weeks with Shengmai improved their cardiac function through a mechanism involving alterations in calcium homeostasis involving enhanced calcium release from the sarcoplasmic reticulum (Zhang et al 2008).…”