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

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.

Exosomes derived from platelet-rich plasma present a novel potential in alleviating knee osteoarthritis by promoting proliferation and inhibiting apoptosis of chondrocyte via Wnt/β-catenin signaling pathway

“…The expression of Wnt5a protein was also increased [42–44]. It has been reported that the Wnt/β-catenin signaling pathway can suppress IL-1β-induced cartilage degradation and inflammatory responses in chondrocytes [45] and downregulate expression of the RUNX2 gene to induce chondrocyte hypertrophy [46]. PRP-Exos-mediated activation of the canonical Wnt/β-catenin signaling pathway needs to be verified.…”

Guava Leaf Extract Suppresses Fructose Mediated Non-Alcoholic Fatty Liver Disease in Growing Rats

“…43 There is large volume of evidence that indicates that fructose-overload activates the Akt/FOXO-1/SREBP1c signaling cascade, and that of hypoxia and inflammation (HIF-1α, VEGF, TNF-α) leading to the pathogenesis of insulin-resistant state. [44][45][46] As these are well-established treatment targets, we report here that, in pubescent rats with ad libitum access to fructose (15%), PG-HM acts as an insulin sensitizer by 1) incrementing signals of energy homeostasis (Akt, p-tyr-STAT -3 and SREBP-1C), 2) mitigating signals of de novo lipogenesis (AMPK alpha1), and hypoxia-inflammation (HIF-1α, VEGF, TNF-α). The PG-HM nullified the fundamental mechanisms involved in glucose intolerance and insulin The effect of PG-HM on molecular markers of hepatic metabolism was confirmed using the immortal, nontumorigenic, human hepatoma cells, HepG2, which were cultured in a fructose-rich environment (1mM), such that the FC2 simulated the hepatic insulin-resistant state with activated mTOR/ p-tyr-STAT-3 and HIF-1α, VEGF and TNF-α signaling pathways.…”

Evaluations of aqueous humor protein markers in different types of glaucoma

“…VEGF, one of the most important inducers of angiogenesis and vascular permeability, also has a strong link with inflammation and immunity [ 23 , 24 ] and can greatly change the tissue microenvironment and induce inflammation. [ 25 , 26 ] Contrary to the sharp rise in VEGF levels in APAC eyes, VEGF remained at a slightly higher level in the CACG eyes, indicating a hypoxic microenvironment in the anterior segment tissues of the CACG and the APAC eyes. It has been postulated that VEGF expression correlate with glaucoma aggressiveness and refractory treatment.…”