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.

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.

• Authors: Mayuko Sakanashi, Toshihiro Matsuzaki, Katsuhiko Noguchi, Junko Nakasone, Makiko Sakanashi, Taro Uchida, Mika Kina-Tanada, Haruaki Kubota, Kumiko Arakaki, Akihide Tanimoto, Nobuyuki Yanagihara, Matao Sakanashi, Yusuke Ohya, Hiroaki Masuzaki, Shogo Ishiuchi, Kazuhiro Sugahara, Masato Tsutsui
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 77 Issue 7 Pg. 1827-37 ( 2013) ISSN: 1347-4820 [Electronic] Japan
• PMID: 23615023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• Muscle Proteins
• Plant Extracts
• sannoshashinto
• Berberine
• Peroxynitrous Acid
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Superoxide Dismutase

Topics

• Animals
• Berberine
• Drugs, Chinese Herbal (pharmacology)
• Female
• Humans
• Medicine, Kampo
• Muscle Proteins (biosynthesis)
• Myocardial Reperfusion Injury (drug therapy, enzymology, physiopathology)
• Myocardium (enzymology)
• Nitric Oxide Synthase Type II (biosynthesis)
• Ovariectomy
• Oxidation-Reduction (drug effects)
• Peroxynitrous Acid (metabolism)
• Plant Extracts (pharmacology)
• Postmenopause (metabolism)
• Rats
• Rats, Wistar
• Superoxide Dismutase (biosynthesis)
• Time Factors