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      Methylophiopogonanone A, an Ophiopogon homoisoflavonoid, alleviates high-fat diet-induced hyperlipidemia: assessment of its potential mechanism

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          Abstract

          Methylophiopogonanone A (MO-A), a homoisoflavonoid extracted from Ophiopogon japonicus, has been shown to attenuate myocardial apoptosis and improve cerebral ischemia/reperfusion injury. However, the hypolipidemic effects remain unknown. This study was performed to investigate a potential hypolipidemic effect of MO-A in hyperlipidemia rats, as well as its underlying mechanism of action. A rat model of hyperlipidemia was induced by a high-fat diet (HFD). Animals were randomly divided into three groups (n=8/group): normal control group (NC), HFD group, and HFD+MO-A (10 mg·kg -1·d -1) treatment group. The effects of MO-A on serum lipids, body weight, activity of lipoprotein metabolism enzyme, and gene expression of lipid metabolism were evaluated in HFD-induced rats. In HFD-induced rats, pretreatment with MO-A decreased the body weight gain and reduced serum and hepatic lipid levels. In addition, pretreatment with MO-A improved the activities of lipoprotein lipase and hepatic lipase in serum and liver, down-regulated mRNA expression of acetyl CoA carboxylase and sterol regulatory element-binding protein 1c, and up-regulated mRNA expression of low-density lipoprotein receptor and peroxisome proliferator-activated receptor α in the liver. Our results indicated that MO-A showed strong ability to ameliorate the hyperlipidemia in HFD-induced rats. MO-A might be a potential candidate for prevention of overweight and dyslipidemia induced by HFD.

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          Most cited references33

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          Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor.

          Epidemiologic data indicate that a postprandial state characterized by abnormally increased levels of glucose and lipids (also referred to as postprandial dysmetabolism) is an independent predictor of future cardiovascular events, even in nondiabetic subjects. The cardiovascular toxicity of postprandial dysmetabolism is mediated by oxidant stress, which is directly proportional to the increase in glucose after a meal. This transient increase in free radicals acutely triggers inflammation, endothelial dysfunction, hypercoagulability, sympathetic hyperactivity, and a cascade of other atherogenic changes. The postprandial dysmetabolism hypothesis has been bolstered by interventional studies that have demonstrated that blunting the postprandial spikes in glucose and lipids improves inflammation and endothelial function immediately. Early randomized controlled trials indicate that reducing postprandial dysmetabolism appears to significantly slow atherosclerotic progression and may improve cardiovascular prognosis. In conclusion, postprandial dysmetabolism appears to be an important proximate cause of adverse cardiovascular events. Addressing this fundamental and largely unrecognized condition will require specific screening and treatment strategies. Diet, exercise, and various pharmacologic agents can improve postprandial dysmetabolism. Using these strategies may help improve the prognosis for patients with diabetes mellitus and/or coronary heart disease.
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            New insights into the pathophysiology of dyslipidemia in type 2 diabetes.

            Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for patients with type 2 diabetes, despite recent significant advances in management strategies to lessen CVD risk factors. A major cause is the atherogenic dyslipidemia, which consists of elevated plasma concentrations of both fasting and postprandial triglyceride-rich lipoproteins (TRLs), small dense low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) cholesterol. The different components of diabetic dyslipidemia are not isolated abnormalities but closely linked to each other metabolically. The underlying disturbances are hepatic overproduction and delayed clearance of TRLs. Recent results have unequivocally shown that triglyceride-rich lipoproteins and their remnants are atherogenic. To develop novel strategies for the prevention and treatment of dyslipidaemia, it is essential to understand the pathophysiology of dyslipoproteinaemia in humans. Here, we review recent advances in our understanding of the pathophysiology of diabetic dyslipidemia.
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              Grifola frondosapolysaccharides ameliorate lipid metabolic disorders and gut microbiota dysbiosis in high-fat diet fed rats

              G. frondosa polysaccharides have the potential to ameliorate lipid metabolic disorders in part through modulating gut microbiota and mRNA expression of genes involved in hepatic lipid and cholesterol metabolism. The purpose of this study was to assess the potential effects of polysaccharides from edible mushroom Grifola frondosa (GFP) on lipid metabolic disorders and gut microbiota dysbiosis, and elucidate their possible regulatory mechanisms on lipid and cholesterol metabolism in high-fat diet (HFD)-exacerbated hyperlipidemic and hypercholesterolemic rats. Results showed that oral administration of GFP markedly alleviated dyslipidaemia through decreasing the serum levels of total triglycerides, total cholesterol, and free fatty acids, and significantly suppressing hepatic lipid accumulation and steatosis. Besides, the excretion of fecal bile acids was also promoted by oral administration of GFP. Metagenomic analysis revealed that GFP supplementation (400 mg kg −1 day −1 ) resulted in significant structure changes on gut microbiota in HFD-fed rats, in particular modulating the relative abundance of functionally relevant microbial phylotypes compared with the HFD group. Key microbial phylotypes responding to GFP intervention were identified to strongly correlate with the lipid metabolism disorder associated parameters using the correlation network based on Spearman's correlation coefficient. Serum and hepatic lipid profiles were found positively correlated with Clostridium -XVIII, Butyricicoccus and Turicibacter , but negatively correlated with Helicobater , Intestinimonas , Barnesiella , Parasutterella , Ruminococcus and Flavonifracter . Moreover, GFP treatment (400 mg kg −1 day −1 ) regulated the mRNA expression levels of the genes responsible for hepatic lipid and cholesterol metabolism. Oral supplementation of GFP markedly increased the mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acid (BA) synthesis and excretion from the liver. These findings illustrated that GFP could ameliorate lipid metabolic disorders through modulating specific gut microbial phylotypes and regulating hepatic lipid and cholesterol metabolism related genes, and therefore could be used as a potential functional food ingredient for the prevention or treatment of hyperlipidemia.
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                Author and article information

                Journal
                Braz J Med Biol Res
                Braz. J. Med. Biol. Res
                bjmbr
                Brazilian Journal of Medical and Biological Research
                Associação Brasileira de Divulgação Científica
                0100-879X
                1414-431X
                02 March 2020
                2020
                : 53
                : 3
                : e9201
                Affiliations
                [1]Center for Translational Medicine of the First Affiliated Hospital, Sun Yatsen University, Guangzhou, China
                Author notes
                Correspondence: Bei-Xin Yu: < yubx3@ 123456mail2.sysu.edu.cn >
                Author information
                http://orcid.org/0000-0001-8279-127X
                http://orcid.org/0000-0002-5289-833X
                http://orcid.org/0000-0002-1920-1529
                Article
                00609
                10.1590/1414-431X20199201
                7057930
                32130294
                43f7fa3b-e3ea-4bd9-91f4-c6f58f353b43

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 August 2019
                : 4 December 2019
                Page count
                Figures: 9, Tables: 2, Equations: 0, References: 31
                Categories
                Research Article

                ophiopogon japonicus,pparα,high-fat diet,lipid lowering,dyslipidemia

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