title: Acute treatment with Danshen-Gegen decoction protects the myocardium against ischemia/reperfusion injury via the redox-sensitive PKCɛ/mK(ATP) pathway in rats.
abstract: Danshen-Gegen (DG) decoction, an herbal formulation comprising Radix Salvia Miltiorrhiza and Radix Puerariae Lobatae, is prescribed for the treatment of coronary heart disease in Chinese medicine. Experimental and clinical studies have demonstrated 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. Short-term treatment with DG extract at a daily dose of 1 g/kg and 2 g/kg for 3 days protected against myocardial I/R injury in rats. The cardioprotection afforded by DG pretreatment was paralleled by enhancements in mitochondrial antioxidant status and membrane structural integrity, as well as a decrease in the sensitivity of mitochondria to Ca²⁺-stimulated permeability transition in vitro, particularly under I/R conditions. Short-term treatment with the DG extract also enhanced the translocation of PKCɛ from the cytosol to mitochondria in rat myocardium, and this translocation was inhibited by α-tocopherol co-treatment with DG extract in rats. Short-term DG treatment may precondition the myocardium via a redox-sensitive PKCɛ/mK(ATP) pathway, with resultant inhibition of the mitochondrial permeability transition through the opening of mitochondrial K(ATP) channels. Our 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, 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; D002316:Cardiotonic Agents / Q000627:therapeutic use; 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 / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000627:therapeutic use*; D018517:Plant Roots / Q000737:chemistry; D015221:Potassium Channels / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D029908:Pueraria / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; C568783:Danshen-Gegen; 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; D024502:alpha-Tocopherol