Bergamot Polyphenols Boost Therapeutic Effects of the Diet on Non-Alcoholic Steatohepatitis (NASH) Induced by “Junk Food”: Evidence for Anti-Inflammatory Activity

Abstract

Wrong alimentary behaviors and so-called “junk food” are a driving force for the rising incidence of non-alcoholic fatty liver disease (NAFLD) among children and adults. The “junk food” toxicity can be studied in “cafeteria” (CAF) diet animal model. Young rats exposed to CAF diet become obese and rapidly develop NAFLD. We have previously showed that bergamot (Citrus bergamia Risso et Poiteau) flavonoids, in the form of bergamot polyphenol fraction (BPF), effectively prevent CAF diet-induced NAFLD in rats. Here, we addressed if BPF can accelerate therapeutic effects of weight loss induced by a normocaloric standard chow (SC) diet. 21 rats fed with CAF diet for 16 weeks to induce NAFLD with inflammatory features (NASH) were divided into three groups. Two groups were switched to SC diet supplemented or not with BPF (CAF/SC±BPF), while one group continued with CAF diet (CAF/CAF) for 10 weeks. BPF had no effect on SC diet-induced weight loss, but it accelerated hepatic lipid droplets clearance and reduced blood triglycerides. Accordingly, BPF improved insulin sensitivity, but had little effect on leptin levels. Interestingly, the inflammatory parameters were still elevated in CAF/SC livers compared to CAF/CAF group after 10 weeks of dietary intervention, despite over 90% hepatic fat reduction. In contrast, BPF supplementation decreased hepatic inflammation by reducing interleukin 6 (Il6) mRNA expression and increasing anti-inflammatory Il10, which correlated with fewer Kupffer cells and lower inflammatory foci score in CAF/SC+BPF livers compared to CAF/SC group. These data indicate that BPF mediates a specific anti-inflammatory activity in livers recovering from NASH, while it boosts lipid-lowering and anti-diabetic effects of the dietary intervention.

Hepatoprotective and Anti-Oxidative Effects of Total Flavonoids From Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on Nonalcoholic Steatohepatitis In Vivo and In Vitro Through Nrf2-ARE Signaling Pathway

“…Flavonoids product has numerous biological properties, which may be promising therapeutic agents for NASH (Li and Schluesener, 2017). Many natural products are rich in flavonoids and possess anti-oxidative and anti-inflammatory activities against NASH (Jian et al, 2018;Parafati et al, 2018;Wang et al, 2018). Various flavonoid compounds have been identified, such as flavones, flavanones, flavanols, flavonols, and chalcones (Rzepecka-Stojko et al, 2015).…”

Modulation of Nitric Oxide Synthases by oxyLDL: Role in Vascular Inflammation and Atherosclerosis Development

“…The balance between protective autophagy and apoptotic cell death by LOX-1 has also been further confirmed by the up-regulation of another marker of autophagy, LC3 II (microtubule associated protein 1A/1B-light chain 3 type II), an effect reverted after LOX-1 silencing, via LOX-1 shRNA[60,61].6. ConclusionTaken together, data reported in this review article suggest that oxyLDL lead to direct andindirect impairment of constitutive release of NO highlighting overexpression of inducible iNOS.…”

“…This suggests that the oxidative stimulus was not able to restore physiologic NO levels early, favouring free radical overproduction and caspase-induced Beclin-1 cleavage; the result of these mechanisms triggered by oxyLDL was represented by a suppression of autophagy associated with an enhanced apoptosis [41,60].…”

Oxidative Imbalance and Kidney Damage: New Study Perspectives from Animal Models to Hospitalized Patients

“…In our experiments, we used an obesity model: cafeteria (CAF) diet-fed rats. In rodents, the CAF diet mimics diet-induced obesity in humans, inducing severe obesity, insulin resistance, and high plasma triglyceride levels [77][78][79]. To analyze obesity-induced organ damage, we hypothesized that the link between obesity and renal impairment could be represented by oxidative stress.…”