The Transcription Profile Unveils the Cardioprotective Effect of Aspalathin against Lipid Toxicity in an In Vitro H9c2 Model.
Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocyte model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 h before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, CD36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results suggest that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.
Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg 7505, South Africa. rabia.johnson@mrc.ac.za.|Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa. rabia.johnson@mrc.ac.za.
Rabia
R
Johnson
Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg 7505, South Africa. pdludla@mrc.ac.za.|Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa. pdludla@mrc.ac.za.
Phiwayinkosi V
PV
Dludla
Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg 7505, South Africa. christo.muller@mrc.ac.za.|Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa. christo.muller@mrc.ac.za.|Department of Biochemistry and Microbiology, University of Zululand, Kwadlangezwa 3886, South Africa. christo.muller@mrc.ac.za.
Christo J F
CJ
Muller
Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg 7505, South Africa. bh3@sun.ac.za.|Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa. bh3@sun.ac.za.
Barbara
B
Huisamen
Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch 7599, South Africa. mfessop@sun.ac.za.
M Faadiel
MF
Essop
Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg 7505, South Africa. johan.louw@mrc.ac.za.|Department of Biochemistry and Microbiology, University of Zululand, Kwadlangezwa 3886, South Africa. johan.louw@mrc.ac.za.
Johan
J
Louw
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000633:toxicity*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome
D002316:Cardiotonic Agents; D047188:Chalcones; D016207:Cytokines; D005227:Fatty Acids; D020738:Leptin; D008055:Lipids; D010936:Plant Extracts; C517016:aspalathin
aspalathin; cardiomyopathy; diabetes mellitus; hyperglycemia; lipotoxicity; polyphenols