MOLECULAR NUTRITION & FOOD RESEARCH
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2018
·Vol. 62
·期 16
·1800170
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IF 5.151
Chun-Feng Guo,Ya-Hong Yuan,Tian-Li Yue,Jing-Yan Li
Scope Rats and hamsters are the most commonly used animal models for evaluating the hypocholesterolemic activity of potential probiotic strains, whereas little or no information has been reported on whether the animal models would affect the experimental conclusions regarding the hypocholesterolemic efficacy of the strains. Methods and results Both high-cholesterol-fed rats and hamsters were intragastrically administered viable cells of bile salt hydrolase-active Lactobacillus acidophilus K16 once daily (1 × 10 10 CFU per kg body weight) for 28 d. It was found that the strain did not significantly ( p > 0.05) affect the serum and hepatic cholesterol levels in rats, whereas it significantly decreased ( p < 0.01 or p < 0.001) the serum total and non-HDL-cholesterol as well as hepatic-free, esterified, and total cholesterol levels in hamsters by 29.6%, 38.8%, 15.8%, 36.2%, and 34.0%, respectively. Conclusion These data suggest that the hypocholesterolemic efficacy of L. acidophilus K16 is substantially different between high-cholesterol-fed hamsters and rats and that hamsters are a better model system than rats for evaluating the hypocholesterolemic efficacy of potential probiotic strains due to their similarity to humans in biliary bile acid composition, including types of bile acids and their conjugation form.
研究领域:
营养学
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微生物学
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动物模型
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION
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2015
·
IF 1.206
Qingyu Wang,Zhongyao Du,Hao Zhang,Liang Zhao,Jing Sun,Xiaonan Zheng,Fazheng Ren
This study aimed to evaluate the beneficial effects of polyphenol extract of adlay (Coix lacryma-jobi L. var. ma-yuen Stapf.) (PEA) on gut microbiota in rats fed a high-cholesterol diet (HCD). Rats were fed HCD containing 1% cholesterol (w/w), with or without a daily intragastric supplement of 200 mg/kg body weight PEA. Results showed that PEA significantly ameliorated increases in serum cholesterol and low-density lipoprotein cholesterol values and significantly restored high-density lipoprotein cholesterol values. The HCD-induced imbalance of gut microflora was modulated by the consumption of PEA. Most bacterial strains influenced by PEA are related to host lipid metabolism. The abundances of one Erysipelotrichales strains and two Clostridia strains were lower in the PEA group than in the control. Phenolic compounds in PEA were identified by HPLC. The findings indicate that PEA may be a useful dietary supplement in the treatment of elevated cholesterol levels and the imbalanced gut microbial ecology.
研究领域:
营养学
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微生物学
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2014
·
IF 4.48
Chun-Feng Guo,Jing-Yan Li
The effects of a Tween 80 and CaCl 2 mixture on the hypocholesterolemic activity of bile salt hydrolase (BSH)-active Lactobacillus casei F0422 were investigated in rats fed a cholesterol-rich diet for 3 weeks. This mixture significantly enhanced the hypocholesterolemic activity of strain F0422 in rats. The group administered drinking water supplemented with both strain F0422 and the Tween 80 and CaCl 2 mixture had significantly lower levels of total serum cholesterol, low-density lipoprotein cholesterol and total liver cholesterol than did the group administered drinking water supplemented only with strain F0422 or the Tween 80 and CaCl 2 mixture. The hypocholesterolemic activity of the combined strain F0422 and Tween 80 and CaCl 2 mixture was attributed to the increase in fecal bile acid excretion through enhancement of bile salt tolerance and BSH catalytic activity of strain F0422 by Tween 80 and up-regulation of the adhesion of strain F0422 to intestinal epithelial cells by CaCl 2 .
研究领域:
营养学
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微生物学
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药理学
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DOI
高影响因子
Materials Advances
·
2022
·Vol. 3
·期 5
·2417-2424
·
IF 0
Yufang Wang,Jianzhu Wang,Mingshuang Sun,Jiyan Zhang,Yanping Bi
Escaping from the immune system to achieve a long circulation time is an essential prerequisite for targeting liposomes. Monomethoxy-poly(ethylene glycol)–distearoylphosphatidylethanolamine (mPEG–DSPE) is the most commonly used stealth polymer for long circulating liposomes. With its monomethoxy end moving freely on the liposomal surface, the linear PEG chains of mPEG–DSPE construct a hydration layer to repel complement proteins and thus evade immune clearance. We describe in this work a new kind of PEG derivative whose two ends were grafted with cholesterol (cholesterol–PEG–cholesterol, CPC). According to the in vitro and in vivo results, the presence of CPC in liposomes was shown to reduce the uptake by phagocyte cells while extending the circulation time. The stealth performance of CPC liposomes is closely related to the molecular weight of PEG moieties. CPC6k performed better than CPC2k, CPC4k and the commonly used mPEG2k–DSPE. CPC on the liposomal surface would not let the free end of PEG act as the immune recognition site, meanwhile, the PEG chain of CPC tends to adopt a twisted ring-like conformation rather than a linear conformation, which is considered to be associated with the stealth effect. This finding adds to the range of stealth liposomes and may be valuable for developing new drug carriers.
研究领域:
药剂学
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生物医学工程
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DOI
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Yao Guo,Guangjie Shu,Ziyang Zhang,Xiaoshuang Hu,Huiru Huang,Wenxin Lu,Miaomiao Zhu,Bing Liu,Shenshen Zhang
Cholesterol homeostasis dysregulation is a primary risk factor for atherosclerosis (AS) development. Fisetin, a flavonoid compound, has shown promise in regulating cholesterol homeostasis by enhancing transintestinal cholesterol excretion (TICE). This study aimed to investigate the regulatory effects and underlying mechanisms of fisetin in AS. In this study, ApoE −/− mice fed a high-fat diet (HFD) were employed to investigate the effects of fisetin on the prevention of AS. Various methods, including biochemical analyses, histopathological staining, lipid deposition assessment, untargeted lipidomics analysis and RNA sequencing, were employed to explore the underlying mechanisms. The results showed that treatment with fisetin notably reduced lipid deposition in the aortic root of HFD-treated ApoE −/− mice and attenuated hepatic lipid deposition and histopathological changes. This was accompanied by decreased serum levels of total cholesterol, triglyceride and LDL cholesterol. Fisetin also effectively mitigated HFD-induced oxidative stress and inflammation in mice. Hepatic lipidomics revealed significant alterations in lipid content and composition following fisetin treatment, including reductions in lipids associated with AS risk, such as cholesteryl ester (ChE), phosphatidylcholines (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), cardiolipin (CL), phosphatidylinositol (PI), and TG. Additionally, phosphatidylserine (PS) levels were increased. RNA sequencing of livers revealed that fisetin affected genes related to cholesterol metabolism and bile acid biosynthesis, including cytochrome P450 ( Cyp ) family and Nr1h4 ( Fxr ). Molecular docking analysis suggested FXR may be a potential target of fisetin. In the liver, cholesterol can be either converted into bile acids or pumped out to bile ducts by ATP-binding cassette (ABC) transporters G5 (ABCG5) and G8 (ABCG8) for elimination. Fisetin treatment notably modulated the hepatic proteins related to cholesterol metabolism (HMGCR, PCSK9, LDLR, FXR, CYP27A1, CYP7A1, CYP8B1 and BSEP) and cholesterol excretion (ABCG5, ABCG8), maintaining cholesterol homeostasis. Additionally, fisetin increased the excretion of fecal neutral sterols, including cholesterol, dihydrocholesterol, and coprosterone. It also increased the expression of FXR, ABCG5, ABCG8, and LDLR, while decreasing NPC1L1 and PCSK9 levels in the jejunum, thereby stimulating the TICE pathway. These findings provide compelling evidence that fisetin reduces cholesterol levels and alleviates AS by stimulating FXR-mediated hepatic cholesterol metabolism and the TICE pathway. The findings suggest that fisetin-regulated cholesterol metabolism may represent a promising therapeutic strategy for the treatment of AS.
研究领域:
药理学
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心血管医学
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生物化学
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分子生物学
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营养科学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Qihan Wang,Weiyi Shen,Wentao Shao,Hai Hu
Berberine (BBR) is a traditional Chinese herb with broad antimicrobial activity . Gut microbiota plays an important role in the metabolism of bile acids and cholesterol. Our study investigated the effects of BBR on alleviating cholesterol and bile acid metabolism disorders induced by high cholesterol diet in mice. Adult male C57BL/6J mice fed with high cholesterol diet (HC) containing 1.25 % cholesterol (HC group) or fed with chow diet containing 0.02 % cholesterol (Chow group) served as controls. BBR50 and BBR100 group mice were fed with HC, and oral BBR daily at doses of 50 or 100 mg/kg respectively for 8 weeks. The results showed that BBR could reshape the homeostasis and composition of gut microbiota. The abundance of Clostridium genera was significantly inhibited by BBR, which resulted in a significant reduction of secondary bile acids within the enterohepatic circulation and a significant lower hydrophobic index of bile acids . The absorption of cholesterol in intestine, the deposition of cholesterol in liver and the excretion of cholesterol in biliary tract were significantly inhibited by BBR, which promoted the unsaturation of cholesterol in bile. These findings suggest the potential utility of BBR as a functional food to alleviate the negative effects of high cholesterol diet.
研究领域:
营养学
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微生物学
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药理学
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DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
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2012
·Vol. 33
·期 7
·909-917
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IF 1.953
Wang Xin-ting,Li Jia,Liu Li,Hu Nan,Jin Shi,Liu Can,Mei Dan,Liu Xiao-dong
Aim: Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions. The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications. Methods: Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats. On d 35 after the injection, liver, heart, intestine, kidney, pancreas, cerebral cortex and hippocampus were isolated from the rats. The content of total and free cholesterol in the tissues was determined using HPLC. The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses, respectively. Results: In diabetic rats, the level of free cholesterol was significantly decreased in the peripheral tissues, but significantly elevated in hippocampus, as compared with those in the control rats. Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues, but significant change was only found in kidney and liver. In diabetic rats, the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex, but the change had no statistical significance. Conclusion: Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus. The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein.
研究领域:
内分泌学
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代谢学
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药理学
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神经科学
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DOI
PubMed
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2021
·Vol. 69
·期 1
·59-66
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IF 1.645
Dong-Dong Li,Pan Yu,Hui Xu,Zhen-Zhong Wang,Wei Xiao,Lin-Guo Zhao
Berberine (BBR), a kind of quaternary ammonium benzylisoquinoline alkaloids with multiple pharmacological activities, has been regarded as a promising lipid-lowering agent in the field of drug repurposing. Particularly, the chemical modification at the C-9 position of BBR can remarkably improve its lipid-lowering efficacy. In this study, thirteen novel BBR derivatives were rationally designed, synthesized, and evaluated by preliminary pharmacological tests. The results showed that most compounds exhibited more potent hypolipidemic activities when compared with BBR and simvastatin. Among these compounds, compound 2h-1 and 2h-2 exhibited better activity profiling in these four tests involving with inhibition of total cholesterol (TCHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) and the increase of high-density lipoprotein cholesterol (HDLC). Correspondingly, the BBR analogs with 9-O-cinnamic moiety probably exhibited potent lipid-lowering activity, and should be exploited as an important versatile template for the development of BBR-like lipid-lowering agents.
研究领域:
药理学
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药物发现
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化学
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DOI
PubMed
高影响因子
OPTIK
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2023
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IF 3.1
Chu Fenghong,Feng Yuan,Hu Anduo,Dai Caihong,Qi Yue,Bian Zhenglan
This paper proposes a cholesterol biosensor with hydrogel optical fiber immobilized with cholesterol oxidase . The hydrogel optical fiber with core and cladding structure was fabricated based on precursor solutions with two different concentrations of polyethylene glycol diacrylate (PEGDA). The concentration of fluorescent indicator in the hydrogel optical fiber core and the thickness of hydrogel cladding were optimized to obtain high performance cholesterol sensing. The sensing characteristics under different laser power, temperature, and pH were investigated. The experimental results showed that the photobleaching was reduced by appropriately decreasing the magnitude of laser power. The fluorescent indicator shows the best efficiency and stability when the ambient temperature is 25 °C and pH is 7. The linearity of the system was greater than 0.997 for cholesterol concentration in the range of 0.5–1.7 mg/mL, with good repeatability and response time of 4 mins. The precision of this sensor is 0.02 mg/mL. The hydrogel optical fiber with the advantage of flexibility, good ion permeability, and biocompatibility has broad application prospect in biomedical.
研究领域:
生物医学工程
·
分析化学
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DOI
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2023
·
IF 4
Wenjing Jiang,Qun Huang,Xiangxing Meng,Rizwan-ur Rehman,Kun Qian,Xu Yang,Xiaozhi Liu,Jingnan Chen,Ye Zhang,Jing Li,Jilite Wang,Qingbin Guo,Suwen Liu,Hao Wang
Ursolic acid (UA) is a natural triterpene carboxylic acid with an underlying anti-hyperlipidemia effect. This study examined the mechanism of interactions of UA with cholesterol esterase (CEase), pancreatic lipase (PL), and micellar cholesterol solubility in vitro. The half-maximal inhibitory concentration (IC50) of CEase, PL, and micellar cholesterol solubility was determined to be 0.07 ± 0.01 mg/mL, 1.81 ± 0.13 mg/mL, and 1.73 ± 0.08 mg/mL, respectively. Multispectral combination revealed that UA changed the secondary structure and quenched the intrinsic fluorescence by static quenching of the two enzymes. The interactions were exothermic reaction as determined by enthalpy. Furthermore, molecular docking confirmed that UA was bound to amino acids of two enzymes at active site through hydrophobic interaction and van der Waals forces. Molecular dynamics (MD) simulation found that CEase and PL rearranged with UA to form stable complexes. The strong inhibition effect of CEase and PL mediated by UA might provide additional insight into understanding the role of UA in the hypolipidemic effect.
研究领域:
生物化学
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药理学
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营养学
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产品关联
DOI
高影响因子
ACS Applied Polymer Materials
·
2024
·
IF 4.4
Cairong Qiao,Ling Qian,Qiang Peng,Wanqing Yue
We constructed heteropolysaccharide-based complex coacervate microdroplets using pectin and DEAE-dextran via electrostatic interactions. The coacervate microdroplets were stable from pH 3 to 12 and completely dissociated at a NaCl concentration of 160 mM. When cholesterol oxidase was distributed in the microdroplets, the enzyme activity of cholesterol oxidase did not decrease, and it was made more stable. Through spiked recovery experiments of cholesterol in serum and a comparison with the results of commercial assay kits, we successfully validated that the assay can be used for the detection of cholesterol in real samples.
研究领域:
生物化学
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分析化学
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材料科学
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产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2022
·Vol. 414
·期 12
·3593-3603
·
IF 4.478
Wu Shuyao,Jiang Meijiao,Mao Hui,Zhao Nan,He Dongqing,Chen Qinan,Liu Daliang,Zhang Wei,Song Xi-Ming
A simple and sensitive electrochemical cholesterol biosensor was fabricated based on ceramic-coated liposome (cerasome) and graphene quantum dots (GQDs) with good conductivity. The cerasome consists of a lipid-bilayer membrane and a ceramic surface as a soft biomimetic interface, and the mild layer-by-layer self-assembled method as the immobilization strategy on the surface of the modified electrode was used, which can provide good biocompatibility to maintain the biological activity of cholesterol oxidase (ChOx). The GQDs promoted electron transport between the enzyme and the electrode more effectively. The structure of the cerasome-forming lipid was characterized by Fourier transform infrared (FT-IR). The morphology and characteristics of the cerasome and GQDs were characterized by transmission electron microscopy (TEM), zeta potential, photoluminescence spectra (PL), etc. The proposed biosensors revealed excellent catalytic performance to cholesterol with a linear concentration range of 16.0 × 10 −6 –6.186 × 10 −3 mol/L, with a low detection limit (LOD) of 5.0 × 10 −6 mol/L. The Michaelis–Menten constant ( K m ) of ChOx was 5.46 mmol/L, indicating that the immobilized ChOx on the PEI/GQDs/PEI/cerasome–modified electrode has a good affinity to cholesterol. Moreover, the as-fabricated electrochemical biosensor exhibited good stability, anti-interference ability, and practical application for cholesterol detection. Graphical abstract
研究领域:
生物医学工程
·
分析化学
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产品关联
DOI
PubMed
高影响因子
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