Specific Compounds Derived from Traditional Chinese Medicine Ameliorate Lipid-Induced Contractile Dysfunction in Cardiomyocytes (2024)

Wang, F., Neumann, D., Kapsokalyvas, D., Hoes, M. F., Schianchi, F., Glatz, J. F. C., Nabben, M. (2024). Specific Compounds Derived from Traditional Chinese Medicine Ameliorate Lipid-Induced Contractile Dysfunction in Cardiomyocytes. International Journal of Molecular Sciences, 25(15), Article 8131. https://doi.org/10.3390/ijms25158131

Wang, Fang ; Neumann, Dietbert ; Kapsokalyvas, Dimitris et al. / Specific Compounds Derived from Traditional Chinese Medicine Ameliorate Lipid-Induced Contractile Dysfunction in Cardiomyocytes. In: International Journal of Molecular Sciences. 2024 ; Vol. 25, No. 15.

@article{ba4094734e604b46a68ce8778c92c46b,

title = "Specific Compounds Derived from Traditional Chinese Medicine Ameliorate Lipid-Induced Contractile Dysfunction in Cardiomyocytes",

abstract = "Chronic lipid overconsumption, associated with the Western diet, causes excessive cardiac lipid accumulation, insulin resistance, and contractile dysfunction, altogether termed lipotoxic cardiomyopathy (LCM). Existing treatments for LCM are limited. Traditional Chinese Medicine (TCM) has been shown as beneficial in diabetes and its complications. The following compounds-Resveratrol, Quercetin, Berberine, Baicalein, and Isorhamnetin-derived from TCM and often used to treat type 2 diabetes. However, virtually nothing is known about their effects in the lipid-overexposed heart. Lipid-induced insulin resistance was generated in HL-1 cardiomyocytes and adult rat cardiomyocytes by 24 h exposure to high palmitate. Upon simultaneous treatment with each of the TCM compounds, we measured myocellular lipid accumulation, insulin-stimulated fatty acid and glucose uptake, phosphorylation levels of AKT and ERK1/2, plasma membrane appearance of GLUT4 and CD36, and expression of oxidative stress-/inflammation-related genes and contractility. In lipid-overloaded cardiomyocytes, all the selected TCM compounds prevented lipid accumulation. These compounds also preserved insulin-stimulated CD36 and GLUT4 translocation and insulin-stimulated glucose uptake in an Akt-independent manner. Moreover, all the TCM compounds prevented and restored lipid-induced contractile dysfunction. Finally, some (not all) of the TCM compounds inhibited oxidative stress-related expression, and others reduced inflammatory expression. Their ability to restore CD36 trafficking makes all these TCM compounds attractive natural supplements for LCM treatment.",

keywords = "adult rat cardiomyocytes, contractile function, endosomal CD36 and GLUT4, insulin resistance, lipotoxic cardiomyopathy, Myocytes, Cardiac/drug effects metabolism, Animals, Rats, Medicine, Chinese Traditional/methods, Insulin Resistance, Myocardial Contraction/drug effects, Glucose/metabolism, Drugs, Chinese Herbal/pharmacology, Lipid Metabolism/drug effects, Oxidative Stress/drug effects, Glucose Transporter Type 4/metabolism genetics, Mice, Cell Line, CD36 Antigens/metabolism genetics, Proto-Oncogene Proteins c-akt/metabolism, Male",

author = "Fang Wang and Dietbert Neumann and Dimitris Kapsokalyvas and Hoes, {Martijn F} and Francesco Schianchi and Glatz, {Jan F C} and Miranda Nabben and Luiken, {Joost J F P}",

year = "2024",

month = jul,

day = "25",

doi = "10.3390/ijms25158131",

language = "English",

volume = "25",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "15",

}

Wang, F, Neumann, D, Kapsokalyvas, D, Hoes, MF, Schianchi, F, Glatz, JFC, Nabben, M 2024, 'Specific Compounds Derived from Traditional Chinese Medicine Ameliorate Lipid-Induced Contractile Dysfunction in Cardiomyocytes', International Journal of Molecular Sciences, vol. 25, no. 15, 8131. https://doi.org/10.3390/ijms25158131

Specific Compounds Derived from Traditional Chinese Medicine Ameliorate Lipid-Induced Contractile Dysfunction in Cardiomyocytes. / Wang, Fang; Neumann, Dietbert; Kapsokalyvas, Dimitris et al.
In: International Journal of Molecular Sciences, Vol. 25, No. 15, 8131, 25.07.2024.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Specific Compounds Derived from Traditional Chinese Medicine Ameliorate Lipid-Induced Contractile Dysfunction in Cardiomyocytes

AU - Wang, Fang

AU - Neumann, Dietbert

AU - Kapsokalyvas, Dimitris

AU - Hoes, Martijn F

AU - Schianchi, Francesco

AU - Glatz, Jan F C

AU - Nabben, Miranda

AU - Luiken, Joost J F P

PY - 2024/7/25

Y1 - 2024/7/25

N2 - Chronic lipid overconsumption, associated with the Western diet, causes excessive cardiac lipid accumulation, insulin resistance, and contractile dysfunction, altogether termed lipotoxic cardiomyopathy (LCM). Existing treatments for LCM are limited. Traditional Chinese Medicine (TCM) has been shown as beneficial in diabetes and its complications. The following compounds-Resveratrol, Quercetin, Berberine, Baicalein, and Isorhamnetin-derived from TCM and often used to treat type 2 diabetes. However, virtually nothing is known about their effects in the lipid-overexposed heart. Lipid-induced insulin resistance was generated in HL-1 cardiomyocytes and adult rat cardiomyocytes by 24 h exposure to high palmitate. Upon simultaneous treatment with each of the TCM compounds, we measured myocellular lipid accumulation, insulin-stimulated fatty acid and glucose uptake, phosphorylation levels of AKT and ERK1/2, plasma membrane appearance of GLUT4 and CD36, and expression of oxidative stress-/inflammation-related genes and contractility. In lipid-overloaded cardiomyocytes, all the selected TCM compounds prevented lipid accumulation. These compounds also preserved insulin-stimulated CD36 and GLUT4 translocation and insulin-stimulated glucose uptake in an Akt-independent manner. Moreover, all the TCM compounds prevented and restored lipid-induced contractile dysfunction. Finally, some (not all) of the TCM compounds inhibited oxidative stress-related expression, and others reduced inflammatory expression. Their ability to restore CD36 trafficking makes all these TCM compounds attractive natural supplements for LCM treatment.

AB - Chronic lipid overconsumption, associated with the Western diet, causes excessive cardiac lipid accumulation, insulin resistance, and contractile dysfunction, altogether termed lipotoxic cardiomyopathy (LCM). Existing treatments for LCM are limited. Traditional Chinese Medicine (TCM) has been shown as beneficial in diabetes and its complications. The following compounds-Resveratrol, Quercetin, Berberine, Baicalein, and Isorhamnetin-derived from TCM and often used to treat type 2 diabetes. However, virtually nothing is known about their effects in the lipid-overexposed heart. Lipid-induced insulin resistance was generated in HL-1 cardiomyocytes and adult rat cardiomyocytes by 24 h exposure to high palmitate. Upon simultaneous treatment with each of the TCM compounds, we measured myocellular lipid accumulation, insulin-stimulated fatty acid and glucose uptake, phosphorylation levels of AKT and ERK1/2, plasma membrane appearance of GLUT4 and CD36, and expression of oxidative stress-/inflammation-related genes and contractility. In lipid-overloaded cardiomyocytes, all the selected TCM compounds prevented lipid accumulation. These compounds also preserved insulin-stimulated CD36 and GLUT4 translocation and insulin-stimulated glucose uptake in an Akt-independent manner. Moreover, all the TCM compounds prevented and restored lipid-induced contractile dysfunction. Finally, some (not all) of the TCM compounds inhibited oxidative stress-related expression, and others reduced inflammatory expression. Their ability to restore CD36 trafficking makes all these TCM compounds attractive natural supplements for LCM treatment.

KW - adult rat cardiomyocytes

KW - contractile function

KW - endosomal CD36 and GLUT4

KW - insulin resistance

KW - lipotoxic cardiomyopathy

KW - Myocytes, Cardiac/drug effects metabolism

KW - Animals

KW - Rats

KW - Medicine, Chinese Traditional/methods

KW - Insulin Resistance

KW - Myocardial Contraction/drug effects

KW - Glucose/metabolism

KW - Drugs, Chinese Herbal/pharmacology

KW - Lipid Metabolism/drug effects

KW - Oxidative Stress/drug effects

KW - Glucose Transporter Type 4/metabolism genetics

KW - Mice

KW - Cell Line

KW - CD36 Antigens/metabolism genetics

KW - Proto-Oncogene Proteins c-akt/metabolism

KW - Male

U2 - 10.3390/ijms25158131

DO - 10.3390/ijms25158131

M3 - Article

SN - 1661-6596

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 15

M1 - 8131

ER -

Wang F, Neumann D, Kapsokalyvas D, Hoes MF, Schianchi F, Glatz JFC et al. Specific Compounds Derived from Traditional Chinese Medicine Ameliorate Lipid-Induced Contractile Dysfunction in Cardiomyocytes. International Journal of Molecular Sciences. 2024 Jul 25;25(15):8131. doi: 10.3390/ijms25158131