title: Long-term treatment with danshen-gegen decoction protects the myocardium against ischemia/reperfusion injury via the redox-sensitive protein kinase C-ε/mK(ATP) pathway in rats.
abstract: Danshen-Gegen (DG) decoction, an herbal formulation comprised of radix Salvia Miltiorrhiza and radix Puerariae Lobata, is prescribed for the treatment of coronary heart disease in Chinese medicine. Experimental and clinical studies have indicated that DG decoction can reduce the extent of atherosclerosis. In the present study, using an ex vivo rat model of myocardial ischemia/reperfusion (I/R) injury, we investigated the myocardial preconditioning effect of an aqueous DG extract prepared from an optimized weight-to-weight ratio of danshen and gegen. Long-term treatment with DG extract at increasing doses (including the equivalent of a human dose) protected against myocardial I/R injury in rats. The cardioprotection afforded by DG pretreatment was paralleled by enhancements in mitochondrial antioxidant status and membrane integrity, as well as a decrease in the sensitivity of mitochondria to Ca(2+)-stimulated permeability transition in vitro, particularly under I/R conditions. Long-term treatment with the DG extract enhanced the translocation of protein kinase C-epsilon (PKCε) from the cytosol to mitochondria in rat myocardium, and this translocation was inhibited by α-tocopherol co-treatment with DG extract in rats. Long-term DG treatment may precondition the myocardium via a redox-sensitive PKCε/mK(ATP) pathway, with resultant inhibition of the mitochondrial permeability transition. The results suggest that clinical studies examining the effectiveness of DG extract given prophylactically in affording protection against myocardial I/R injury would be warranted.
authors.affiliation: Section of Biochemistry and Cell Biology, Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors.forename: Po Yee
authors.initials: PY
authors.lastname: Chiu
authors.forename: Sze Man
authors.initials: SM
authors.lastname: Wong
authors.forename: Hoi Yan
authors.initials: HY
authors.lastname: Leung
authors.forename: Pou Kuan
authors.initials: PK
authors.lastname: Leong
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.forename: Limin
authors.initials: L
authors.lastname: Zhou
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zuo
authors.forename: Philip Y
authors.initials: PY
authors.lastname: Lam
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000627:therapeutic use*; D015221:Potassium Channels / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza; D015398:Signal Transduction
chemical_list: D004365:Drugs, Chinese Herbal; D010618:Phenanthrolines; D015221:Potassium Channels; D017382:Reactive Oxygen Species; C117780:mitochondrial K(ATP) channel; C028972:dan-shen root extract; D045304:Cytochromes c; D051744:Protein Kinase C-epsilon