title: Similar to spironolactone, oxymatrine is protective in aldosterone-induced cardiomyocyte injury via inhibition of calpain and apoptosis-inducing factor signaling.
abstract: Accumulating evidence indicates that oxymatrine (OMT) possesses variously pharmacological properties, especially on the cardiovascular system. We previously demonstrated that activated calpain/apoptosis-inducing factor (AIF)-mediated pathway was the key molecular mechanism in aldosterone (ALD) induces cardiomyocytes apoptosis. In the present study, we extended the experimentation by investigating the effect of OMT on cardiomyocytes exposed to ALD, as compared to spironolactone (Spiro), a classical ALD receptor antagonist. Cardiomyocytes were pre-incubated with OMT, Spiro or vehicle for 1 h, and then, cardiomyocytes were exposed to ALD 24 h. The cell injury was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) leakage ratio. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, annexin V/PI staining, and relative caspase-3 activity assay. Furthermore, expression of pro-apoptotic proteins including truncated Bid (tBid), calpain and AIF were evaluated by western blot analysis. ALD stimulation increased cardiomyocytes apoptosis, caspase-3 activity and protein expression of calpain, tBid and AIF in the cytosol (p<0.05). Pre-incubated with cardiomyocytes injury and increased caspase-3 activity were significantly attenuated (p<0.05). Furthermore, OMT suppressed ALD-induced high expression of calpain and AIF. And these effects of OMT could be comparable to Spiro. These findings indicated that OMT might be a potential cardioprotective-agent against excessive ALD-induced cardiotoxicity, at least in part, mediated through inhibition of calpain/AIF signaling.
authors.affiliation: Research Division of Pharmacology, Guiyang Medical University, Guiyang, China ; School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tang, Kowloon, Hong Kong, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Xiao
authors.affiliation: Research Division of Pathophysiology, Guiyang Medical University, Guiyang, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Research Division of Pharmacology, Guiyang Medical University, Guiyang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Research Division of Pharmacology, Guiyang Medical University, Guiyang, China.
authors.forename: Cong-Hui
authors.initials: CH
authors.lastname: Bai
authors.affiliation: Research Division of Pharmacology, Guiyang Medical University, Guiyang, China ; School of Life Science,Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Xiang-Chun
authors.initials: XC
authors.lastname: Shen
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000235:genetics* / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061251:Primary Cell Culture; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013148:Spironolactone / Q000494:pharmacology*; D000093842:Matrines
chemical_list: D000450:Aldosterone; D000470:Alkaloids; D051033:Apoptosis Inducing Factor; D051023:BH3 Interacting Domain Death Agonist Protein; D002154:Calpain; D053148:Caspase 3; D007770:L-Lactate Dehydrogenase; D011807:Quinolizines; D013148:Spironolactone; C494831:Aifm1 protein, rat; C494816:Bid protein, rat; C037573:oxymatrine; D000093842:Matrines