NAFLD and Atherosclerosis Are Prevented by a Natural Dietary Supplement Containing Curcumin, Silymarin, Guggul, Chlorogenic Acid and Inulin in Mice Fed a High-Fat Diet.

Antonella Amato,Sara Baldassano,Marta Di Carlo,Pasquale Picone,Flavia Mulè,Manfredi Rizzo,Gaetano-Felice Caldara,Domenico Nuzzo

doi:10.3390/nu9050492

Abstract

Non-alcoholic fatty liver disease (NAFLD) confers an increased risk of cardiovascular diseases. NAFDL is associated with atherogenic dyslipidemia, inflammation and renin-angiotensin system (RAS) imbalance, which in turn lead to atherosclerotic lesions. In the present study, the impact of a natural dietary supplement (NDS) containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin on NAFLD and atherosclerosis was evaluated, and the mechanism of action was examined. C57BL/6 mice were fed an HFD for 16 weeks; half of the mice were simultaneously treated with a daily oral administration (os) of the NDS. NAFLD and atherogenic lesions in aorta and carotid artery (histological analysis), hepatic expression of genes involved in the NAFLD (PCR array), hepatic angiotensinogen (AGT) and AT1R mRNA expression (real-time PCR) and plasma angiotensin (ANG)-II levels (ELISA) were evaluated. In the NDS group, steatosis, aortic lesions or carotid artery thickening was not observed. PCR array showed upregulation of some genes involved in lipid metabolism and anti-inflammatory activity (Cpt2, Ifng) and downregulation of some genes involved in pro-inflammatory response and in free fatty acid up-take (Fabp5, Socs3). Hepatic AGT, AT1R mRNA and ANG II plasma levels were significantly lower with respect to the untreated-group. Furthermore, NDS inhibited the dyslipidemia observed in the untreated animals. Altogether, these results suggest that NDS prevents NAFLD and atherogenesis by modulating the expression of different genes involved in NAFLD and avoiding RAS imbalance.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is the most frequent hepatic disorder in developed countries and may lead to steatohepatitis, cirrhosis and liver cancer
This study aims to investigate whether the treatment with this natural dietary supplement (NDS) is able to prevent the development of NAFLD and related atherosclerotic lesions in aorta and carotid artery in a mouse model of diet-induced obesity (DIO)
At the end of the treatment, the untreated mice had greater mass gain compared to the animals treated with NDS (Figure 1A), no difference in the food intake was observed (Figure 1B)

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the most frequent hepatic disorder in developed countries and may lead to steatohepatitis, cirrhosis and liver cancer. Nutrients 2017, 9, 492 progression of NAFLD remains unclear increased fatty acid syntheses, oxidative stress and inflammation may play a fundamental role [2]. Emerging evidence suggests that angiotensin (ANG) II, a pro-oxidant cytokine, synthesized mainly from the hepatic precursor angiotensinogen (AGT), may have a relevant importance in the pathogenesis of NAFLD by generating reactive oxygen species and regulating the production of pro-inflammatory mediators [3]. Patients with NAFLD present elevated ANG II levels [4,5], and animals with liver steatosis show increased hepatic expression of AGT, AGT II and ANG II type 1 receptor (AT1 R) [6,7]. Increasing clinical evidence supports a strong association between NAFLD and cardiovascular diseases (CVD), which represents the principal cause of death in NAFLD patients, more so than liver-related complications [9,10].

Objectives

Methods

Results

Conclusion