Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice

Zhu, Rongshu; Sun, Yandi; Hou, Yuting; Fan, Jungang; Chen, Gang; Li, Tuoping

doi:10.1016/j.cbi.2017.05.018

Cited by 40 publications

(25 citation statements)

References 34 publications

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“…It is an effective method for cholesterol homeostasis in vivo ( 23 ) and a protective mechanism to contract atherosclerotic injury ( 32 ). Various cholesterol transporters, including SR-BI, ABCG5, ABCG8 and CYP7A1 are associated with RCT, and increase cholesterol transportation and conversion ( 33 ). Therefore, medicines which regulate expression of these proteins are potential candidates for hypercholesterolemia treatment.…”

Section: Discussionmentioning

confidence: 99%

Effects of mulberry leaf on experimental hyperlipidemia rats induced by high‑fat diet

et al. 2018

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Hypercholesterolemia is a major risk factor for cardiovascular disease. Mulberry leaf (ML) is a Traditional Chinese Medicine used to treat hyperlipidemia in clinical settings. The aim of the present study was to identify the potential effect and possible target of ML in anti-hypercholesterolemia. Male Sprague-Dawley rats were fed with a high-fat diet and treated with ML for 5 weeks. Blood lipid levels, total cholesterol (TC) and total bile acid (TBA) in the liver and feces were measured to assess the effects of ML on hypercholesterolemia. Harris's hematoxylin staining and oil red O staining was applied to observe the pathological change and lipid accumulation in the liver. Immunohistochemical assay was performed to observe the location of expressions of scavenger receptor class B type I and low-density lipoprotein (LDL) receptor (-R), and western blotting was applied to determine the protein expression of ATP-binding cassette transporter G5/G8 (ABCG5/8), nuclear transcription factor peroxisome proliferator-activated receptor-α (PPARα), farnesoid-X receptor (FXR) and cholesterol 7α-hydroxylase 1 (CYP7A1). The results demonstrated that ML treatment reduced serum TC and LDL-cholesterol levels, and liver TC and TBA contents; increased serum HDL-C levels, and fecal TC and TBA contents; and alleviated hepatocyte lipid degeneration. In addition, ML treatment inhibited liver LDL-R, PPARα and FXR protein expression, promoted protein expression of CYP7A1, and maintained the ratio of ABCG5/ABCG8. The findings of the present study provide a positive role of ML on cholesterol clearance via promoting cholesterol and TBA execration via FXR- and CYP7A1-mediated pathways; RCT regulation may be a potential mechanism of ML on anti-hypercholesterolemia.

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Section: Discussionmentioning

confidence: 99%

Effects of mulberry leaf on experimental hyperlipidemia rats induced by high‑fat diet

et al. 2018

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“…Therefore, increased excretion of BAs in the feces will promote the conversion from cholesterol to BAs and consequently reduce its release into the systemic circulation. Many studies have demonstrated that fecal BA excretion is increased by pectin consumption (Matheson and Story, 1994;Matheson et al, 1995;Ghaffarzadegan et al, 2016;Zhu et al, 2017b). Yet it is not fully understood how pectin interacts with intestinal BA transport.…”

Section: Introductionmentioning

confidence: 99%

Effects of dietary pectin on the profile and transport of intestinal bile acids in young pigs

Wei

Zhang

Meng

et al. 2018

Journal of Animal Science

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Pectin has been known to lower circulating cholesterol by interacting with bile acid (BA) metabolism. The current study was aimed to investigate intestinal BA transport at the molecular level in a pig model. Twelve young pigs (11.05 ± 0.11 kg) were randomly divided into 2 groups and fed corn-soybean meal diets with either 5% pectin or cornstarch for 72 d. In pigs fed with pectin, total cholesterol and low-density lipoprotein cholesterol (LDL-C) were lowered but high-density lipoprotein (HDL-C) was increased (P < 0.05). Serum triglycerides tended to be lower in the pectin-fed animals (P = 0.093), whereas no change was noted in serum total bile acid. Along the length of the intestine, the size and composition of BA pools vary. The ratio of primary, secondary, taurine-conjugated, and glycine-conjugated BAs in the ileal pool was about 46:15:9:30, whereas it was 28:61:1:11 in the cecum and 22:65:3:9 in the colon (P < 0.05). In the feces, lithocholic acid and ursodeoxycholic acid (UDCA) made up of over 97% of the total BA pool. Overall, the ileum had the greatest expression of farnesoid X receptor (FXR) and apical sodium-coupled bile acid transporter (ASBT) than the duodenum, jejunum, cecum, and colon (P < 0.05), whereas organic solute transporters α/β (OSTα/β) gene expression was peaked in the ileum and jejunum (P < 0.05). Expression multidrug resistance protein 2 (MRP2) gradually decreased towards the end of the intestine (P < 0.05). Greater expression of G protein-coupled bile acid receptor and multidrug resistance protein 3 (MRP3) was found in the cecum and colon (P < 0.05). In pigs fed with 5% pectin, only cecal UDCA (P = 0.097) and hyocholic acid (P = 0.088) showed a decreasing tendency. But FXR, ASBT, and MRP2 were upregulated in the ileum and FXR, OSTα/β, MRP2, and MRP3 in the cecum of PEC-fed pigs (P < 0.05). Liver enzymes involved in BA biosynthesis (CYP7A1, CYP27A1, bile acid-CoA synthase, and bile acid-CoA:amino acid N acyltransferase) were not affected by pectin consumption. In conclusion, the abundant distribution of BA transporters and the greater BA pool size suggests the ileum as the major site for intestinal BA reabsorption in pigs. In the ileum, pectin increased in-and-out BA transport on the apical membrane by increasing ASBT and MRP2, but it increased the overall BA transport in the cecum by increasing OSTα/β and MRP3.

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“…The liver plays an important role in the synthesis and net excretion of cholesterol either directly as free cholesterol in the bile or after its conversion into bile acid, initiated by cholesterol 7α-hydroxylase (CYP7A1) [18,19]. CYP7A1 plays an important role in cholesterol metabolism [20,21]. …”

Section: Introductionmentioning

confidence: 99%

Effects of an Enriched Extract of Paeoniflorin, a Monoterpene Glycoside used in Chinese Herbal Medicine, on Cholesterol Metabolism in a Hyperlipidemic Rat Model

Zhu

Shi

et al. 2017

Med Sci Monit

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BackgroundPaeoniflorin is a monoterpene glycoside extracted from the roots of Paeonia lactiflora and is used in Chinese herbal medicine to treat hyperlipidemia. The aim of this study was to evaluate the effects of an enriched extract of paeoniflorin on cholesterol levels, hemodynamics, and oxidative stress in a hyperlipidemic rat model.Material/MethodsMale Sprague-Dawley rats were fed high-cholesterol diets and treated with three different doses of paeoniflorin for 12 weeks. The effects of paeoniflorin treatment were assessed on cholesterol levels, cholesterol metabolism, red blood cell vascular flow using hemorheology, antioxidant enzymes, and expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR). Rat liver histology and immunohistochemical analysis were performed to evaluate the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), cytochrome P450 7A1 (CYP7A1), and peroxisome proliferator-activated receptors (PPAR)-α. Protein expression HMG-CoAR, low-density lipoprotein receptor (LDLR), PPAR-α and CYP7A1 was measured by Western blotting. Antioxidant activity in rat liver was determined by measuring superoxide dismutase (SOD) and malondialdehyde (MDA).ResultsSerum and hepatic cholesterol, hepatic steatosis and the products of cholesterol metabolism were reduced by paeoniflorin treatment, which also reduced the activity of HMG-CoAR and upregulated the expression of LDLR, PPAR-α, and CYP7A1 expression, increased SOD, decreased MDA, and upregulated Nrf2 expression.ConclusionsThe findings of this study in a rat model of hyperlipidemia have shown that paeoniflorin regulates hepatic cholesterol synthesis and metabolism and may also protect the liver from oxidative stress.

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Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice

Cited by 40 publications

References 34 publications

Effects of mulberry leaf on experimental hyperlipidemia rats induced by high‑fat diet

Effects of mulberry leaf on experimental hyperlipidemia rats induced by high‑fat diet

Effects of dietary pectin on the profile and transport of intestinal bile acids in young pigs

Effects of an Enriched Extract of Paeoniflorin, a Monoterpene Glycoside used in Chinese Herbal Medicine, on Cholesterol Metabolism in a Hyperlipidemic Rat Model

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