Long-Term Treatment With San’o-Shashin-To, a Kampo Medicine, Markedly Ameliorates Cardiac Ischemia-Reperfusion Injury in Ovariectomized Rats via the Redox-Dependent Mechanism

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  • Sakanashi Mayuko
    Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
  • Matsuzaki Toshihiro
    Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
  • Noguchi Katsuhiko
    Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
  • Nakasone Junko
    Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
  • Sakanashi Makiko
    Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus
  • Uchida Taro
    Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
  • Kina-Tanada Mika
    Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
  • Kubota Haruaki
    Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus
  • Arakaki Kumiko
    Third, Departments of Internal Medicine, Graduate School of Medicine, University of the Ryukyus
  • Tanimoto Akihide
    Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences
  • Yanagihara Nobuyuki
    Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health
  • Sakanashi Matao
    Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
  • Ohya Yusuke
    Third, Departments of Internal Medicine, Graduate School of Medicine, University of the Ryukyus
  • Masuzaki Hiroaki
    Second, Departments of Internal Medicine, Graduate School of Medicine, University of the Ryukyus
  • Ishiuchi Shogo
    Department of Neurosurgery, Graduate School of Medicine, University of the Ryukyus
  • Sugahara Kazuhiro
    Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus
  • Tsutsui Masato
    Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus

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Abstract

Background: Hormone replacement therapy has failed to reduce ischemic cardiovascular events in climacteric women. To explore alternative therapy, we examined whether san’o-shashin-to (TJ-113), a kampo medicine, ameliorates cardiac ischemia-reperfusion (IR) injury in a climacteric rat model. Methods and Results: Cardiac function and infarct size after IR were significantly exacerbated in ovariectomized rats as compared with sham-operated rats, whereas long-term treatment with a clinical dosage of TJ-113 for 4 weeks markedly improved these functional and morphological changes. Myocardial inducible nitric oxide synthase (iNOS) expression and peroxynitrite levels were significantly higher in ovariectomized rats compared with sham-operated rats, and long-term TJ-113 treatment significantly reduced these oxidative changes. Furthermore, myocardial manganese superoxide dismutase (Mn-SOD) activity was significantly lower in ovariectomized than in sham-operated rats, and long-term TJ-113 treatment significantly restored antioxidant activity. Importantly, those beneficial actions of TJ-113 were significantly inhibited by the estrogen receptor antagonist, fulvestrant, and the phytoestrogen, emodin, a TJ-113 ingredient, mimicked the actions of TJ-113, suggesting involvement of emodin in the effects of TJ-113. Conclusions: These results provide the first evidence that long-term treatment with a clinical dosage of TJ-113 markedly ameliorates cardiac IR injury in ovariectomized rats via inhibition of iNOS expression, suppression of peroxynitrite formation, and restoration of Mn-SOD activity. TJ-113 may be a novel therapeutic option in the treatment of ischemic heart disease in climacteric women.  (Circ J 2013; 77: 1827–1837)<br>

Journal

  • Circulation Journal

    Circulation Journal 77 (7), 1827-1837, 2013

    The Japanese Circulation Society

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