Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction.Protocatechuic aldehyde(PCA)is a major phenolic acid in Chinese herb Danshen(Salvia miltiorrhiza root).This st...Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction.Protocatechuic aldehyde(PCA)is a major phenolic acid in Chinese herb Danshen(Salvia miltiorrhiza root).This study investigated whether PCA regulated nuclear pyruvate kinase isoform M2(PKM2)function to protect cardiomyocytes.In rats subjected to isoprenaline,PCA attenuated heart injury and protected cardiomyocytes from apoptosis.Through DARTS and CETSA assays,we identified that PCA bound and promoted PKM2 nuclear translocation in cardiomyocytes exposed to oxygen/glucose deprivation(OGD).In the nucleus,PCA increased the binding of PKM2 to β-Catenin via preserving PKM2 acetylation,and the complex,in cooperation with T-cell factor 4(TCF4),was required for transcriptional induction of genes encoding anti-apoptotic proteins,contributing to rescuing cardiomyocyte survival.In addition,PCA ameliorated mitochondrial dysfunction and prevented mitochondrial apoptosis dependent on PKM2.Consistently,PCA increased the binding of PKM2 to β-Catenin,improved heart contractive function,normalized heart structure and attenuated oxidative damage in mice subjected to artery ligation,but the protective effects were lost in Pkm2-deficient heart.Together,we showed that PCA regulated nuclear PKM2 function to rescue cardiomyocyte survival via β-Catenin/TCF4 signaling cascade,suggesting the potential of pharmacological intervention of PKM2 shuttle to protect the heart.展开更多
Objective A reversed-phase HPLC method was established for the simultaneous determination of five hydrophilic and lipophilic components in the roots of Salvia miltiorrhiza. Methods Hydrophilic components including dan...Objective A reversed-phase HPLC method was established for the simultaneous determination of five hydrophilic and lipophilic components in the roots of Salvia miltiorrhiza. Methods Hydrophilic components including danshensu, protocatechuic aldehyde, and salvianolic acid B, and lipophilic components such as cryptotanshinone and tanshinone liA, were successfully separated on a Waters Symmetry C18 reverse- phase column （250 mm×4.6 mm, 5 μm）, with acetonitrile-0.5% phosphoric acid （gradient elution） as mobile phase, the detection wavelength was set at 281 nm with flow rate of 1.0 mL/min, and the column temperature was maintained at 30 ~C. Results The recovery of the method was in the range of 95.1%-102.5% and the precision was less than 3% for all five analytes. All the compounds showed good linearity （R2 〉 0.9990） in a relatively wide concentration range. Therefore, this HPLC method demonstrated good reproducibility, stability, and accuracy in validation studies. Conclusion Simultaneous quantification of the multiple components by HPLC would be a better strategy for the quality evaluation on the roots of S. miltiorrhiza.展开更多
基金supported by the National Key R&D Program of China(2019YFC1711000)the National Natural Science Foundation of China(81421005 and 81722048)“Double First-Class”University project(CPU2018GF04 and CPU2018GY09,China)。
文摘Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction.Protocatechuic aldehyde(PCA)is a major phenolic acid in Chinese herb Danshen(Salvia miltiorrhiza root).This study investigated whether PCA regulated nuclear pyruvate kinase isoform M2(PKM2)function to protect cardiomyocytes.In rats subjected to isoprenaline,PCA attenuated heart injury and protected cardiomyocytes from apoptosis.Through DARTS and CETSA assays,we identified that PCA bound and promoted PKM2 nuclear translocation in cardiomyocytes exposed to oxygen/glucose deprivation(OGD).In the nucleus,PCA increased the binding of PKM2 to β-Catenin via preserving PKM2 acetylation,and the complex,in cooperation with T-cell factor 4(TCF4),was required for transcriptional induction of genes encoding anti-apoptotic proteins,contributing to rescuing cardiomyocyte survival.In addition,PCA ameliorated mitochondrial dysfunction and prevented mitochondrial apoptosis dependent on PKM2.Consistently,PCA increased the binding of PKM2 to β-Catenin,improved heart contractive function,normalized heart structure and attenuated oxidative damage in mice subjected to artery ligation,but the protective effects were lost in Pkm2-deficient heart.Together,we showed that PCA regulated nuclear PKM2 function to rescue cardiomyocyte survival via β-Catenin/TCF4 signaling cascade,suggesting the potential of pharmacological intervention of PKM2 shuttle to protect the heart.
基金National Department Public Benefit Research Foundation(201107011)
文摘Objective A reversed-phase HPLC method was established for the simultaneous determination of five hydrophilic and lipophilic components in the roots of Salvia miltiorrhiza. Methods Hydrophilic components including danshensu, protocatechuic aldehyde, and salvianolic acid B, and lipophilic components such as cryptotanshinone and tanshinone liA, were successfully separated on a Waters Symmetry C18 reverse- phase column （250 mm×4.6 mm, 5 μm）, with acetonitrile-0.5% phosphoric acid （gradient elution） as mobile phase, the detection wavelength was set at 281 nm with flow rate of 1.0 mL/min, and the column temperature was maintained at 30 ~C. Results The recovery of the method was in the range of 95.1%-102.5% and the precision was less than 3% for all five analytes. All the compounds showed good linearity （R2 〉 0.9990） in a relatively wide concentration range. Therefore, this HPLC method demonstrated good reproducibility, stability, and accuracy in validation studies. Conclusion Simultaneous quantification of the multiple components by HPLC would be a better strategy for the quality evaluation on the roots of S. miltiorrhiza.
