title: 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.
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.
  
  
  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.
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. mayuko@med.u-ryukyu.ac.jp
authors.forename: Mayuko
authors.initials: M
authors.lastname: Sakanashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Noguchi
authors.forename: Junko
authors.initials: J
authors.lastname: Nakasone
authors.forename: Makiko
authors.initials: M
authors.lastname: Sakanashi
authors.forename: Taro
authors.initials: T
authors.lastname: Uchida
authors.forename: Mika
authors.initials: M
authors.lastname: Kina-Tanada
authors.forename: Haruaki
authors.initials: H
authors.lastname: Kubota
authors.forename: Kumiko
authors.initials: K
authors.lastname: Arakaki
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
authors.forename: Matao
authors.initials: M
authors.lastname: Sakanashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Shogo
authors.initials: S
authors.lastname: Ishiuchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugahara
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
mesh_terms: D000818:Animals; D001599:Berberine; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020835:Medicine, Kampo; D009124:Muscle Proteins / Q000096:biosynthesis; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010052:Ovariectomy; D010084:Oxidation-Reduction / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D017698:Postmenopause / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D004365:Drugs, Chinese Herbal; D009124:Muscle Proteins; D010936:Plant Extracts; C062798:sannoshashinto; D001599:Berberine; D030421:Peroxynitrous Acid; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase