Sheng-Mai-San attenuates contractile dysfunction and structural damage induced by chronic intermittent hypoxia in mice.
Sheng-Mai-San (SMS), a well-known Chinese medicinal plant formula, is widely used for the treatment of cardiac diseases characterized by deficiency of Qi and Yin syndrome. A mouse chronic intermittent hypoxia (CIH) model was established to mimic the primary clinical features of deficiency of Qi and Yin syndrome. Mice experienced CIH for 28 days (nadir 7% to peak 8% oxygen, 20 min per day), resulting in left ventricle (LV) dysfunction and structure abnormalities. After administration of SMS (0.55, 1.1, and 5.5 g·kg(-1)·d(-1)) for four weeks, improved cardiac function was observed, as indicated by the increase in the ejection fraction from the LV on echocardiography. SMS also preserved the structural integrity of the LV against eccentric hypotrophy, tissue vacuolization, and mitochondrial injury as measured by histology, electron microscopy, and ultrasound assessments. Mechanistically, the antioxidant effects of SMS were demonstrated; SMS was able to suppress mitochondrial apoptosis as indicated by the reduction of several pro-apoptotic factors (Bax, cytochrome c, and cleaved caspase-3) and up-regulation of the anti-apoptosis factor Bcl-2. In conclusion, these results demonstrate that SMS treatment can protect the structure and function of the LV and that the protective effects of this formula are associated with the regulation of the mitochondrial apoptosis pathway.
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
Wei-Lan
WL
Mo
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
Cheng-Zhi
CZ
Chai
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
Jun-Ping
JP
Kou
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
Yong-Qing
YQ
Yan
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China; Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, China. Electronic address: boyangyu59@163.com.
Bo-Yang
BY
Yu
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia; D008297:Male; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism*; D008517:Phytotherapy; D019413:Qi; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000975:Antioxidants; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D051028:bcl-2-Associated X Protein; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; D045304:Cytochromes c; D053148:Caspase 3; D010100:Oxygen
Chronic intermittent hypoxia; Contractile dysfunction; Left ventricle; Mitochondrial apoptosis; Sheng-Mai-San