The Transcription Profile Unveils the Cardioprotective Effect of Aspalathin against Lipid Toxicity in an In Vitro H9c2 Model

Abstract

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.

An In Vitro Study on the Combination Effect of Metformin and N-Acetyl Cysteine against Hyperglycaemia-Induced Cardiac Damage

“…The following day, to assess the ability of NAC plus MET to attenuate high glucose-induced cardiac injury, H9c2 cardiomyoblasts were treated with either 1 mM NAC, 1 µM MET or a combination of NAC plus MET for 24 h. Cells exposed to either normal glucose (NG; 5.5 mM) or HG were treated with the vehicle control. All treatment doses were based on results obtained from previous studies [4,7,[18][19][20][21].…”

Dietary Polyphenols and Gene Expression in Molecular Pathways Associated with Type 2 Diabetes Mellitus: A Review

“…In obese diabetic mice, treatment with 5 and 10 µM PA suppressed NF-κB and TNF-α in both adipose and liver tissue, in a dose-dependent manner [145]. Coupled with its insulin signalling ameliorating effects, as mentioned above, ASP has also been proven to downregulate inflammatory genes suppressor of cytokine signalling 3 (Socs3), tumour necrosis factor receptor superfamily (Tnfsf ), CD44, JAK/STAT and MAPK) and pro-apoptotic genes (Mapk3, optic atrophy 1 (Opa1) and Chuck) by neutralising intracellular ROS and reducing DNA nick formation [104].…”

Rooibos (Aspalathus linearis) and Honeybush (Cyclopiaspp.): From Bush Teas to Potential Therapy for Cardiovascular Disease

“…UCP3 and UCP2 act in concert in the mitochondrial antioxidant response with UCP2 appearing to play a greater cytoprotective role in cardiomyocytes [73]. In the diabetic (db/db) mouse model, aspalathin increased Nrf2 expression as well as its downstream gene targets [74]. High dose aspalathin (130 mg/kg) also ameliorated the effects of hyperglycaemia in the heart by reducing the expected left ventricular enlargement.…”

“…Rooibos may be exerting anti-diabetic effects by affecting the metabolism and uptake of glucose. Aspalathin influences key genes involved in the metabolism of lipids, insulin resistance, inflammation and apoptosis, possibly reversing metabolic abnormalities by involving PPARγ, Adipoq, IL-6/Jak2 pathway and Bcl-2 [74]. PPAG increased beta cell mass and delayed hyperglycaemia in STZ-diabetic mice [147].…”