Capparis spinosa improves non-alcoholic steatohepatitis through down-regulating SREBP-1c and a PPARα-independent pathway in high-fat diet-fed rats.

OBJECTIVE: Non-alcoholic steatohepatitis (NASH) has become a global medical problem. Currently, there is no approved pharmacologic treatment for this condition. Previous studies have suggested that in the pathogenesis of this disease, regulatory pathways associated with de novo lipogenesis and ß-oxidation pathways genes are misregulated. Capparis spinosa (CS) belongs to the family of Capparidaceae and is a traditional plant used to treat various diseases, particularly dyslipidemia. The compounds and extracts of this plant in In vivo and in vitro studies resulted in a reduction in lipid profiles and glucose. However, the mechanism of these effects remains unknown. This study aimed to evaluate the effects of (CS) fruit extract on NASH compared to fenofibrate and explored the related molecular mechanism. RESULTS: In the rats (n = 40) model of NASH, biochemical and histopathological examinations showed that liver steatosis, inflammation, and hepatic fibrosis were markedly attenuated in response to CS and fenofibrate interventions. At the molecular level, CS treatment down-regulated sterol regulatory element-binding protein-1c (SREBP-1c) (p < 0.001), acetyl-CoA carboxylase (ACC) (p < 0.001), and up-regulated Carnitine palmitoyltransferase I (CPT1) expression (p < 0.001). In conclusion, CS has favorable therapeutic effects for NASH, which was associated with ameliorating steatosis and fibrosis via regulation of the DNL and ß-oxidation pathway genes.

Effect of Quercetin on the fructose-activated human hepatic stellate cells, LX-2, an in-vitro study.

BACKGROUND: Hepatic fibrosis is one of the main reasons for mortality in the world. Hepatic stellate cells (HSCs) activate during chronic liver injury, express more Transforming growth factor beta (TGF-ß), Collagen1α (COLA1) and actin-alpha smooth muscle (αSMA) that lead to hepatic fibrosis. Quercetin is a flavonoid in vegetables and fruits that has shown hepatoprotective potential, but little is known about its effects on HSCs activation. In this study, we investigated the antifibrotic activity of Quercetin on fructose-activated human HSCs and its underlying mechanism in vitro. METHODS: First, the human HSCs were treated with fructose (25 mM) for 48 h and then with Quercetin for 24 h. Total RNAs were extracted, reversely transcribed into cDNA, Quantitative Real-time PCR and western blot were performed. RESULTS: The results showed that the levels of mRNA expression of TGF-ß, αSMA, Collagen1 genes, and phosphorylated smad3 protein were significantly reduced in fructose-activated HSCs after treatment with Quercetin compared to fructose-activated HSCs. CONCLUSION: Quercetin is effective in reducing the expression of fibrogenic genes in fructose-activated human HSCs through downregulation of the TGF-ß/smad3 signaling pathway. Therefore, Quercetin possesses significant antifibrotic properties in hepatic fibrosis.

Saroglitazar improved hepatic steatosis and fibrosis by modulating inflammatory cytokines and adiponectin in an animal model of non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have become significant global health concerns. In the present study, we aimed to investigate the effects of saroglitazar, a dual PPARα/γ agonist, fenofibrate, a PPAR-α agonist, and pioglitazone, a PPAR-γ agonist on an animal model of NASH. METHODS: Male Wistar rats were fed a high-fat (HF) emulsion via gavage for 7 weeks to induce NASH. The HF-treated rats were grouped into four groups to receive saroglitazar, pioglitazone, fenofibrate, or vehicle. We measured body and liver weight, liver enzymes, serum levels of adiponectin and leptin. We also performed histopathological examinations and gene expression analysis of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF- α), transforming growth factor-beta (TGF-ß), and monocyte chemoattractant protein 1 (MCP-1). RESULTS: Body weight was markedly normalized by both saroglitazar and fenofibrate, while the liver index only decreased significantly with saroglitazar. Saroglitazar corrected ALT, AST, leptin, and adiponectin levels better than pioglitazone and fenofibrate. All PPAR agonists significantly attenuated the upregulation of the proinflammatory and TGF-ß genes, which correlated with the improved steatosis, inflammation of liver tissue, and fibrotic lesions. CONCLUSIONS: As documented by our results, the dual activation of PPARα/γ by saroglitazar could effectively improve steatosis, fibrosis, and aspects of necro-inflammation in the HF-induced NASH model more than fenofibrate and pioglitazone, and it can be more beneficial in the management of NASH.

Capparis spinosa improves the high fat diet-induced non-alcoholic steatohepatitis in rats: the possible role of FGF21.

OBJECTIVES: This study focused on the beneficial effects of Capparis spinosa (CS) treatment on the steatohepatitis induced by the administration of a high-fat emulsion in rats. Changes of hepatic expression and secretion of fibroblast growth factor 21 (FGF21) were also evaluated as a probable mechanism of the CS effects on fatty liver. Male Wistar rats were allocated in different groups to receive a normal diet (NC group), a high-fat diet (HF group), or the high-fat emulsion plus CS extract at a dose of 20 mg/kg (HF+CS group). Body and liver weight, liver index, serum biochemical factors, histopathological examination, and serum level and hepatic gene expression of FGF21 were determined. RESULTS: CS administration markedly reduced liver weight and index, serum levels of glucose, lipids, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and improved histological features of nonalcoholic steatohepatitis (NASH) which were induced by HF feeding in this model. CS supplementation also restored the decreased hepatic and serum FGF21 levels in the fatty liver rats. We propose that the FGF21 up-regulation may partly account for the favorable effects of CS in this steatohepatitis model.

The possible global hazard of cell phone radiation on thyroid cells and hormones: a systematic review of evidences.

The aim of this review was to investigate the effects of possible harmful waves from either cell phone use or being within the range of the cell phone from 450 to 3800 MHz on the thyroid cells and hormones. Eight electronic datasets were systematically searched using MeSH terms, including "cell phone," "mobile phone," "GSM," "radio frequency," "smartphone," "triiodothyronine," "thyroxin," "thyroid-stimulating hormone," "T3," "T4," "TSH," and "morphological" and all possible combinations, to identify relevant studies published up to Dec 2018. We also manually searched the reference lists of potentially selected studies to identify further relevant publications. About 161 relevant studies were initially found. After screening titles and abstracts, 139 studies were excluded, and finally 22 studies (comprising 7182 cases) were included in the qualitative synthesis. Of the 22 included studies, 11 studies reported changes in T3 and T4 levels (six reported a decrease in T3 levels and one reported increase in it); moreover, five found decreased T4 levels and two studies an increased level. In other 10 studies, TSH alteration was reported. Of these, two studies reported a decrease in TSH level and one reported an increase in the hormone levels, while in the remaining studies non-significant changes were reported. Finally, seven studies examined histological changes in the thyroid gland follicles and showed that the volume of these cells was reduced. Based on the evidence discussed above, the reduction in diameter of thyroid follicles is potentially linked with cell phone radiation. Exposure may negatively influence the iodine uptake in the thyroid gland or increases temperature effect on the thyroid gland. However, further research are needed in order to show that the level of TSH and thyroid hormone suppression by microwave.