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      Effect of a stilbene glycoside-rich extract from Polygoni Multiflori Radix on experimental non-alcoholic fatty liver disease based on principal component and orthogonal partial least squares discriminant analysis

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          Abstract

          Polygoni Multiflori Radix is a traditional Chinese medicine used clinically to support the functions of the liver and kidneys and to treatment hyperlipidemia. In previous studies, an effective fraction, rich in 2,3,5,4′-tetrahydroxy stilbene-2-O-β-D-glucoside (TSG), was separated from Polygoni Multiflori Radix and demonstrated hypolipidemic activity. The present study aimed to systematically assess the effect of this fraction on non-alcoholic fatty liver disease (NAFLD). A NAFLD model was established by feeding Sprague-Dawley rats a high-fat diet with 10% fructose solution for 18 weeks. Hematoxylin and eosin staining was applied for hepatic histopathological analysis. In addition, enzyme activities, lipid metabolism, inflammatory factors and insulin resistance indices were measured using a fully automatic blood biochemistry analyser and ELISA. Furthermore, cytochrome P450 2E1 (CYP2E1) and peroxisome proliferator-activated receptor α (PPARα) mRNA and protein expression were evaluated using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Principal component analysis and orthogonal partial least squares discriminant analysis were used to analyse the data. The results revealed that the TSG-rich fraction (TSGP) significantly lowered the serum total cholesterol and triglyceride levels, and the liver free fatty acid, CYP2E1 mRNA and malondialdehyde levels, in addition to mitigating hepatic enlargement and alleviating liver steatosis. Furthermore, it upregulated PPARα mRNA expression in the liver tissue. The results indicated that TSGP exhibited a protective effect against NAFLD and the underlying mechanism may involve augmentation of anti-lipid peroxidation capacity via regulation of PPARα and CYP2E1-mediated pathways.

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          Nonalcoholic fatty liver disease: pathology and pathogenesis.

          Nonalcoholic fatty liver disease (NAFLD) is recognized as the leading cause of chronic liver disease in adults and children. NAFLD encompasses a spectrum of liver injuries ranging from steatosis to steatohepatitis with or without fibrosis. Fibrosis may progress to cirrhosis and complications including hepatocellular carcinoma. Histologic findings represent the complexity of pathophysiology. NAFLD is closely associated with obesity and is most closely linked with insulin resistance; the current Western diet, high in saturated fats and fructose, plays a significant role. There are several mechanisms by which excess triglycerides are acquired and accumulate in hepatocytes. Formation of steatotic droplets may be disordered in NAFLD. Visceral adipose tissue dysfunction in obesity and insulin resistance results in aberrant cytokine expression; many cytokines have a role in liver injury in NAFLD. Cellular stress and immune reactions, as well as the endocannabinoid system, have been implicated in animal models and in some human studies.
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            In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases.

            Although oxidative stress is an important candidate in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), the localization and pathological significance of oxidative stress-induced cellular damage in NAFLD remains unclear. Hepatic expression of 4-hydroxy-2'-nonenal (HNE) and 8-hydroxydeoxyguanosine (8-OHdG), as reliable markers of lipid peroxidation and oxidative DNA damage, respectively, was immunohistochemically investigated in NAFLD and the results were compared with histological findings. While no HNE adducts were observed in control livers, they were frequently detected in NAFLD. In NASH, the localization of the adducts was in the cytoplasm of sinusoidal cells and hepatocytes with a predominance in zone 3. The grade of necro-inflammation as well as the stage of fibrosis significantly correlated with the HNE index. Regarding 8-OHdG, although no 8-OHdG expression was observed in normal liver and only a few in fatty liver, 11 of 17 cases (64.7%) with NASH exhibited nuclear expression of 8-OHdG in hepatocytes and sinusoidal cells in areas of active inflammation. The 8-OHdG index significantly correlated with the grade of necro-inflammation. Oxidative cellular damage occurs frequently in livers with NAFLD and may be associated with some clinico-pathological features of NAFLD including liver fibrosis and possibly, hepatocarcinogenesis.
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              A consensus orthogonal partial least squares discriminant analysis (OPLS-DA) strategy for multiblock Omics data fusion.

              Omics approaches have proven their value to provide a broad monitoring of biological systems. However, as no single analytical technique is sufficient to reveal the full biochemical content of complex biological matrices or biofluids, the fusion of information from several data sources has become a decisive issue. Omics studies generate an increasing amount of massive data obtained from different analytical devices. These data are usually high dimensional and extracting knowledge from these multiple blocks is challenging. Appropriate tools are therefore needed to handle these datasets suitably. For that purpose, a generic methodology is proposed by combining the strengths of established data analysis strategies, i.e. multiple kernel learning and OPLS-DA to offer an efficient tool for the fusion of Omics data obtained from multiple sources. Three real case studies are proposed to assess the potential of the method. A first example illustrates the fusion of mass spectrometry-based metabolomic data acquired in both negative and positive electrospray ionisation modes, from leaf samples of the model plant Arabidopsis thaliana. A second dataset involves the classification of wine grape varieties based on polyphenolic extracts analysed by two-dimensional heteronuclear magnetic resonance spectroscopy. A third case study underlines the ability of the method to combine heterogeneous data from systems biology with the analysis of publicly available data related to NCI-60 cancer cell lines from different tissue origins, which include metabolomics, transcriptomics and proteomics. The fusion of Omics data from different sources is expected to provide a more complete view of biological systems. The proposed method was demonstrated as a relevant and widely applicable alternative to handle efficiently the inherent characteristics of multiple Omics data, such as very large numbers of noisy collinear variables.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                November 2017
                22 September 2017
                22 September 2017
                : 14
                : 5
                : 4958-4966
                Affiliations
                [1 ]College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
                [2 ]Zhejiang Provincial Key Laboratory of Pharmacological Research of TCM on Hypertension and Related Diseases, Hangzhou, Zhejiang 315053, P.R. China
                [3 ]College of Pharmaceutical Science, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China
                Author notes
                Correspondence to: Professor Guiyuan Lv or Dr Zhaohuan Lou, College of Pharmaceutical Science, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, Zhejiang 310053, P.R. China, E-mail: zjtcmlgy@ 123456163.com , E-mail: lou_jasmine@ 123456163.com
                Article
                ETM-0-0-5197
                10.3892/etm.2017.5197
                5704276
                a35e660d-f308-4198-9a66-483abbb2a35f
                Copyright: © Lou et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 07 November 2016
                : 07 July 2017
                Categories
                Articles

                Medicine
                stilbene glycoside,non-alcoholic fatty liver disease,peroxisome proliferator-activated receptor α,cytochrome p450 2e1,principal component analysis,orthogonal partial least squares discriminant analysis

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