title: Ginsenoside-Rb1 and tetramethylpyrazine phosphate act synergistically to prevent dilated cardiomyopathy in cTnTR141W transgenic mice.
abstract: Ginsenoside-Rb1 (Rb1) is known to be partially associated with the inhibition of heparin-binding epidermal growth factor-like growth factor (HB-EGF). Tetramethylpyrazine phosphate (TMPP) inhibits the activation of the calcium/calmodulin/calmodulin-dependent protein kinase (Ca²⁺/CaM/CaMKII) pathway. The α-myosin heavy chain cTnT(R141W) transgenic mouse was previously reported as a model for dilated cardiomyopathy (DCM), and it was used to test the effects of combinations of Rb1 and TMPP in reversing the progression of DCM and the potential mechanism. Survival, echocardiography, histologic features assessed the effectiveness of Rb1 and TMPP treatments. Western blot and reverse transcription polymerase chain reactions were used to determine expression levels of certain genes. This study clearly demonstrated that treatment with a combination of Rb1 and TMPP could inhibit the expression of HB-EGF, calmodulin1 (Calm1), and calcium/calmodulin-dependent protein kinase II beta (Camk2b). Rb1 alone mainly reduced the expression of HB-EGF, and TMPP alone mainly reduced the expression of Calm1 and Camk2b. Treatment with Rb1 and TMPP had synergistic effects on the amelioration of chamber dilation, contractile dysfunction, interstitial fibrosis, and ultrastructural degeneration in cTnT(R141W) mice when compared with the results of treatment with Rb1 or TMPP alone, and those were probably due to the inhibition of both HB-EGF and the Ca²⁺/CaM/CaMKII pathway.
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Shao
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Ge
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Ma
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.forename: Lian-Feng
authors.initials: LF
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D018450:Disease Progression; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000187:drug effects*; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002147:Calmodulin; D036145:Ginsenosides; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011719:Pyrazines; C442759:ginsenoside Rb1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium; C017953:tetramethylpyrazine