Abstract
Using an ex vivo model of isolated–perfused rat hearts and cultured H9c2 cells, the structure–activity relationships of schisandrin B (Sch B), and analogs lacking either the methylendioxy group or cyclooctadiene ring, schisandrin A (Sch A) and dimethyl diphenyl bicarboxylate (DDB), respectively, were investigated. Pretreatment with Sch B, but not with Sch A or DDB, protected against myocardial ischemia–reperfusion (I-R) injury in rats. Although Sch B pretreatment largely prevented H9c2 cells from menadione-induced cytotoxicity, Sch A pretreatment produced only a marginal protection. However, DDB pretreatment did not cause any detectable effect. The myocardial and cellular protection afforded by Sch B pretreatment correlated with increases in mitochondrial ATP generation capacity and/or reduced glutathione level as well as heat shock protein (Hsp)25/70 expression, under both control and oxidative stress conditions. The results indicate that the methylenedioxy group and the cyclooctadiene ring are important structural determinants of Sch B in enhancing mitochondrial functional ability and glutathione status, as well as tissue Hsp25/70 expression, thereby protecting the myocardium against I-R injury.
Similar content being viewed by others
Change history
15 November 2023
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s11010-023-04900-2
References
Yim TK, Ko KM: Schisandrin B protects against myocardial ischemia–reperfusion injury by enhancing myocardial glutathione antioxidant status. Mol Cell Biochem 196: 151–156, 1999
Yim TK, Ko KM: Methylenedioxy group and cyclooctadiene ring as structural determinants of schisandrin in protecting against myocardial ischemia–reperfusion injury. Biochem Pharmacol 57: 77–81, 1999
Chiu PY, Ko KM: Time-dependent enhancement in mitochondrial glutathione status and ATP generation capacity by schisandrin B treatment decreases the susceptibility of rat hearts to ischemia–reperfusion injury. Biofactors 19: 43–51, 2003
Chiu PY, Ko KM: Schisandrin B protects myocardial ischemia–reperfusion injury partly by inducing Hsp25 and Hsp70 expression in rats. Mol Cell Biochem 266: 139–144, 2004
Floreani M, Carpenedo F: One- and two-electron reduction of menadione in guinea-pig and rat cardiac tissue. Gen Pharmacol 23: 757–762, 1992
Ip SP, Poon MK, Wu SS, Che CT, Ng KH, Kong YC, Ko KM: Effect of schisandrin B in hepatic glutathione antioxidant system in mice: protection against carbon tetrachloride toxicity. Planta Med 61: 398–401, 1995
Hescheler J, Meyer R, Plant S, Xrautwurst D, Rosenthal W, Schultz G: Morphological, biochemical and electrophysiological characterization of a clonal cell (H9c2) line from rat heart. Circ Res 69: 1476–1486, 1991
Chiu PY, Mak DHF, Poon MKT, Ko KM: In vivo antioxidant action of a lignan-enriched extract of schisandra fruit and an anthraquinone-containing extract of Polygonum root in comparison with schisandrin B and emodin. Planta Med 68: 951–956, 2002
Griffith OW: Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106: 207–212, 1980
Ip SP, Che CT, Kong YC, Ko KM: Effects of schisandrin B pretreatment on tumor necrosis factor-κ-induced apoptosis and HSP 70 expression in mouse liver. Cell Stress Chaperones 6: 44–48, 2001
Pagliaro P, Mancardi D, Rastaldo R, Penna C, Gattullo D, Miranda KM, Feelisch M, Wink DA, Paolocci N: Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning. Free Radic Biol Med 34: 33–43, 2003
Inserte J, Garcia-Dorado D, Agullo L, Paniagua A, Soler-Solen J: Urodilatin limits acute reperfusion injury in the isolated rat heart. Cardiovasc Res 45: 351–359, 2000
Boveris A, Chance B: The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 134: 707–716, 1973
Fernandez-Checa JC, Garcia-Ruiz C, Collel A, Morales A, Mari M, Miranda M, Ardite E: Oxidative stress: role of mitochondria and protection by glutathione. Biofactors 8: 7–11, 1998
Davey GP, Peuchen S, Clark JB: Energy thresholds in brain mitochondria. J Biol Chem 273: 12753–12757, 1998
Ward A, McBurney A, Lunec J: Evidence for the involvement of oxygen-derived free radicals in ischaemia–reperfusion injury. Free Radic Res 20: 21–28, 1994
Tritto I, Duilio C, Santoro G, Elia PP, Cirillo P, De Simone C, Chiariello M, Ambrosio G: A short burst of oxygen radicals at reflow induces sustained release of oxidized glutathione from postischemic hearts. Free Radic Biol Med 24: 290–297, 1998
Tappel AL, Zalkin H: Lipid peroxidation in isolated mitochondria. Arch Biochem Biophys 80: 326–332, 1959
Meister A, Anderson ME: Glutathione. Annu Rev Biochem 52: 711–760, 1983
Biagioli B, Scolletta S, Marchetti L, Tabucchi A, Carlucci F: Relationships between hemodynamic parameters and myocardial energy and antioxidant status in heart transplantation. Bioemed Pharmacother 57: 156–162, 2003
Parsell DA, Linquist-McKenzie S: Heat shock proteins and stress tolerance. In: R.I. Morimoto, A. Tissieres, C. Georgopoulos (eds). The Biology of Heat Shock Proteins and Molecular Chaperones. Cold Spring Harbour Laboratory Press, Plainview, 1994, pp 457–494
Escobedo J, Pucci AM, Koh TJ: HSP25 protects skeletal muscle cells against oxidative stress. Free Radic Biol Med 37: 1455–1462, 2004
Hamilton KL, Staib JL, Phillips T, Hess A, Lennon SL, Powers SK: Exercise, antioxidants, and HSP72 protection against myocardial ischemia/reperfusion. Free Radic Biol Med 34: 800–809, 2003
Mallouk Y, Vayssier-Taussat M, Bonventre JV, Polla BS: Heat shock protein 70 and ATP as partners in cell homeostasis. Int J Mol Med 4: 463–474, 1999
Iwaki K, Chi SH, Dillmann WH, Mestril R: Induction of HSP70 in cultured rat neonatal cardiomyocytes by hypoxia and metabolic stress. Circulation 87: 2023–2032, 1993
Iyanagi T, Yamazaki I: One-electron transfer reaction in biochemical systems. V. Difference in the mechanism of quinone reduction by the NADH dehydrogenase and the NAD(P)H dehydrogenase (DT-diaphorase). Biochim Biophy Acta 216: 282–294, 1970
Fleming I: Cytochrome P450 and vascular homeostasis. Circ Res 89: 753–762, 2001
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Ko, K.M., Chiu, P.Y. RETRACTED ARTICLE: Structural determinants of schisandrin B which enhance mitochondrial functional ability and glutathione status as well as heat shock protein expression in rat hearts and H9c2 cells. Mol Cell Biochem 276, 227–234 (2005). https://doi.org/10.1007/s11010-005-4539-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-005-4539-1