Saeng-Ji-Hwang has a protective effect on adriamycin-induced cytotoxicity in cardiac muscle cells.
This study examined the effect of Saeng-Ji-Hwang (SJH: Radix Rehmanniae) on cardiac muscle cells. Adriamycin-exposed H9C2 cardiac muscle cells were treated with a water extract of SJH. The adriamycin induced cell death and caspase-3 activation were significantly inhibited by SJH (2 mg/ml), which can be explained by the increase in Bcl-2 expression and the inhibition of Bax expression. Adriamycin reduced the Mn-SOD protein expression level in H9C2 cardiac muscle cells but a SJH treatment partially but significantly reversed this effect. Manganese (Mn)-TBAP or Mn-TMyM--mitochondria-specific SOD mimetic agent--reduced the adriamycin-induced cytotoxicity. It was also shown that SJH inhibits the release of H2O2 and prevents lipid peroxidation in the presence of adriamycin. This study examined the intracellular GSH level, which showed that adriamycin significantly decreased the intracellular GSH level but SJH increased it. BSO, a selective inhibitor of glutamyl cysteinyl ligase, which is a rate-limiting enzyme in GSH synthesis, did not affect the viability of the cardiac muscle cells. However, a combination of BSO with SJH in the presence of adriamycin reversed the SJH-induced protection. Overall, the results suggest that SJH-associated Mn-SOD and GSH are important factors in the mechanism of the SJH-induced protective mechanism in H9C2 cardiac muscle cells.
Chae
Han-Jung
HJ
Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Jeonju, Chonbuk 560-180, Republic of Korea. soowan@moak.chonbuk.ac.kr
Kim
Hyung-Ryong
HR
Kim
Do-Sung
DS
Woo
Eun-Rhan
ER
Cho
Yong-Gon
YG
Chae
Soo-Wan
SW
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis; D006861:Hydrogen Peroxide / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D032267:Rehmannia / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000903:Antibiotics, Antineoplastic; D004365:Drugs, Chinese Herbal; D019253:Proto-Oncogene Proteins c-bcl-2; C500222:Saeng-Ji-Hwang; D051028:bcl-2-Associated X Protein; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione