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Aegle marmelos differentially affects hepatic markers of glycolysis, insulin signalling pathway, hypoxia, and inflammation in HepG2 cells grown in fructose versus glucose-rich environment

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Abstract

Fructose consumption is responsible for the onset of insulin resistance (IR), and metabolic syndrome. It possesses no functional utility in body and its detrimental effects on hepatic metabolic milieu are beyond those produced by glucose. The need of the hour is to identify fructose-induced IR as an unique pathological state to be managed differentially. The effect of aqueous leaf extract of Aegle marmelos (AM) on hepatic markers of insulin resistance using HepG2 cells cultured in either fructose or glucose-rich environment is investigated. Human hepatocellular carcinoma cells (HepG2) were grown under standard conditions in either—DMEM without glucose (NC), DMEM with high glucose 25 mM (Glu), DMEM-glucose+0.55 mM fructose (FC1), DMEM-glucose+1 mM fructose (FC2) or DMEM-glucose+1 mM fructose+0.1 µM insulin (FC3). The cells were treated with either AM, rutin, quercetin, metformin or pioglitazone and assessed for levels of hexokinase, phosphofructokinase (PFK), aldehyde dehydrogenase, phosphatidylinositol kinase (PI3K), signal transducer and activator of transcription-3 (STAT-3), mitochondrial target of rapamycin (mTOR), hypoxia-induced factor (HIF-1α), vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF-α). Summarily, when results from fructose- and glucose-rich environment were compared, then (1) IR was more pronounced in former; (2) AM performed better in former; (3) metformin and pioglitazone were equivocal in either; (4) rutin and quercetin showed deviant effects from AM; and lastly (5) effects of rutin were closer to AM than quercetin. We hypothesize that AM ameliorates fructose-induced IR through a mechanism which is distinct from standard drugs and not shared by individual phytoconstituents in toto.

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Authors and Affiliations

  1. Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Pushp Vihar, Sector-3, MB Road, New Delhi, 110017, India

    H. Aggarwal, J. Nair, P. Sharma, R. Sehgal, U. Naeem, P. Rajora & R. Mathur

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  1. H. Aggarwal
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  2. J. Nair
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  3. P. Sharma
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  4. R. Sehgal
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  7. R. Mathur
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Correspondence to R. Mathur.

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Aggarwal, H., Nair, J., Sharma, P. et al. Aegle marmelos differentially affects hepatic markers of glycolysis, insulin signalling pathway, hypoxia, and inflammation in HepG2 cells grown in fructose versus glucose-rich environment. Mol Cell Biochem 438, 1–16 (2018). https://doi.org/10.1007/s11010-017-3108-8

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  • DOI: https://doi.org/10.1007/s11010-017-3108-8

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