4-Guanidino-n-butyl syringate (Leonurine, SCM 198) protects H9c2 rat ventricular cells from hypoxia-induced apoptosis.
In the present study, we examined the ability of a chemically synthesized compound based on the structure of leonurine, a phytochemical component of Herba leonuri, to protect H9c2 rat ventricular cells from apoptosis induced by hypoxia and serum deprivation, as a model of ischemia. The results revealed a concentration-dependent increase in cell viability associated with leonurine treatment, accompanied by a consistent decline in lactate dehydrogenase leakage into the culture medium. The fraction of annexin V-fluorescein isothiocyanate-positive cells was increased by hypoxia but reduced by leonurine. These changes were associated with increased expression of the antiapoptotic gene, Bcl-2, and reduced expression of the proapoptotic gene, Bax. Leonurine also reduced the cytosolic Ca overload induced by hypoxia. These results suggest that leonurine elicits potent cardioprotective effects in H9c2 cells, and these effects may be mediated by inhibition of intracellular Ca overload and apoptosis during hypoxia.
Liu
Xin-hua
XH
Department of Pharmacology, Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Chen
Pei-fang
PF
Pan
Li-long
LL
Silva
Ranil De
RD
Zhu
Yi-zhun
YZ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005434:Flow Cytometry; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015394:Molecular Structure; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D013482:Superoxide Dismutase / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
C494828:Bax protein, rat; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C013587:leonurine; D005707:Gallic Acid; D045304:Cytochromes c; D013482:Superoxide Dismutase; D002118:Calcium