CHINESE CHEMICAL LETTERS
·
2016
·
IF 1.947
Hong-Lei Xie,Chun-Chi Liu,Yi-Qun Li,Chang-Lin Bai,Chen-Zhou Hao,Jing Guo,Chang-Qun Luo,Dong-Mei Zhao,Mao-Sheng Cheng
A novel series of β -propanamide derivatives as inhibitors of cholesteryl ester transfer protein (CETP) were synthesized. Previously, H3 (IC 50 2 μmol/L) was observed to inhibit CETP moderately (Xie et al ., 2016). Structural modifications based on H3 led to discovery of the successful CETP inhibitor, known as 1-methyl-4-arylpyrazole. Using a similar approach, compound Q08 was identified as a highly potent CETP inhibitor with an IC 50 of 490 nmol/L in vitro .
研究领域:
药物化学
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生物化学
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DOI
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2023
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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
JOURNAL OF FOOD SCIENCE
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2018
·Vol. 83
·期 10
·2448-2456
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IF 2.018
Xiaohui Zhao,Banmacailang Dong,Pi Li,Wei Wei,Jun Dang,Zenggeng Liu,Yanduo Tao,Hongping Han,Yun Shao,Huilan Yue
Lycium ruthenicum Murr. (LRM, Solanaceae), also called “black wolfberry” in China, is extremely tolerant drought. Although black wolfberry has seeds that are rich in oil, being considered as a potential alternative for edible oil production, little information has been found regarding its characterization. The present study evaluated the fatty acid profile of the seed oil and its phytosterol contents. Moreover, its antioxidant potential and its inhibition activities on pancreatic lipase, and cholesterol esterase (CEase) were also determined. The key fatty acids of studied oil were linoleic (74.58%), oleic (11.82%), γ -linolenic (6.60%), palmitic (4.88%), and stearic (1.40%) acids, which together comprised 99.28% of the total fatty acids. Phytosterols including 24-methylenecholesterol, campesterol, stigmasterol, dihydrolanosterol, 24-methyldesmosterol, β -sitosterol, Δ 5 -avenasterol, cycloartenol, and Δ 7− avenasterol were identified for the 1st time. The inhibition values (IC 50 ) for the DPPH and ABTS radical scavenging capacities of the oil were 7.86 and 15.49 mg/mL, respectively. Additionally, LRM seed oil was also demonstrated to possess strong pancreatic lipase, and CEase inhibition activities with IC 50 values of 12.38 and 2.63 mg/mL, respectively. The mechanism study indicated that the inhibitory manner of the oil on CEase belonged to uncompetitive inhibition of reversible inhibition. The results derived from above studies suggest that LRM seed oil could be a potential source of high value phytochemicals for developing novel functional food.
研究领域:
食品科学
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植物化学
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营养学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2023
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IF 3.4
Zhiquan Wang,Zhe Wang,Miao Lin,Bowen Zheng,Jinlan Zhang
Hyperlipidemia is a global metabolic disorder characterized by dysregulation of lipid metabolism. This dysregulation is closely associated with the altered homeostasis of cholesterol-cholesteryl ester (CE) metabolism in systemic circulation , and some organs. Additionally, the relationship between oxidized cholesteryl ester (oxCE) and the disease has also gained attention. Currently, there is a lack of comprehensive research on the alterations in cholesterol-CE metabolism in the context of hyperlipidemia, as well as the characteristics of lipid-lowering agents in regulating this metabolic state. Therefore, 40 oxCEs were identified in the hamster liver sample, and novel ultrahigh performance liquid chromatography−tandem mass spectrometry (UHPLC-MS/MS) methods were established for simultaneous analysis of cholesterol, 57 CEs, and 40 oxCEs in the serum, liver, adipose tissue, and intestine of hyperlipidemic hamsters. This study investigated the metabolic alterations between cholesterol-CE/oxCE in hyperlipidemic hamsters and those treated with lipid-lowering agents, including the Niemann-Pick-C1 like-1 protein (NPC1L1) inhibitor ezetimibe and the acyl coenzyme A : cholesterol acyltransferase (ACAT) inhibitor avasimibe . The study findings demonstrate metabolic disorders in cholesterol-CE/oxCE homeostasis in hyperlipidemic hamsters. Lipid-lowering agent therapy can improve the metabolic dysregulation caused by hyperlipidemia, with distinct characteristics: ezetimibe is more effective in reducing cholesterol, while avasimibe is more effective in reducing CEs/oxCEs. Eight potential biomarkers indicating the dysregulation of cholesterol-CE metabolism caused by hyperlipidemia and its improvement by lipid-lowering agents have been identified in the serum. This study offers new insights into the hyperlipidemia pathophysiology and the mechanisms of lipid-lowering agents from a novel perspective on cholesterol-CE/oxCE metabolic homeostasis.
研究领域:
代谢学
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药理学
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脂质组学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Zixing Chen,Chi Ho Jacky Chau,Andrew Erickson,Huafang Ding,Shouhe Huang,Wen-Sen He,Hanyue Zhu,Zhen-Yu Chen
Phytosterols have long been used to prevent hypercholesterolemia-related diseases, although their effects on intestinal cholesterol metabolism remain elusive. This study applied comparative proteomics to investigate the effects of various sterols on proteomic changes in differentiated Caco-2 cells. A total of 206, 231, 180, and 197 differentially expressed proteins were identified following treatment with cholesterol, β-sitosterol, stigmasterol, and campesterol, respectively. Functional enrichment analysis revealed that phytosterols significantly altered the proteome of Caco-2 cells, though their effect on cholesterol transport protein expression was negligible. Notably, while phytosterols did not regulate the expression of acyl-CoA:cholesterol acyltransferase 2 (ACAT2), β-sitosterol and stigmasterol significantly lowered the level of cholesterol oleate in Caco-2 cells by 57.1 ± 0.8% and 51.4 ± 3.9%, respectively, demonstrating that they inhibited ACAT2-catalyzed cholesteryl esterification activity. In view of the fact that cholesterol needs to be converted to cholesteryl esters before incorporation into chylomicrons, it was concluded that phytosterols primarily reduce intestinal cholesterol absorption by inhibiting ACAT2 enzyme activity rather than its gene expression. This study provides new insights into the regulation of cholesterol homeostasis by phytosterols in the small intestine.
研究领域:
营养生物化学
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分子生物学
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细胞生物学
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脂质代谢
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药理学
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
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2022
·Vol. 14
·期 6
·1273
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IF 6.525
Jingjing Ye,Min Gong,Jian Song,Shu Chen,Qinghan Meng,Rui Shi,Liqun Zhang,Jiajia Xue
Chronic inflammation plays a side effect on tissue regeneration, greatly inhibiting the repair or regeneration of tissues. Conventional local delivery of anti-inflammation drugs through physical encapsulation into carriers face the challenges of uncontrolled release. The construction of an inflammation-responsive prodrug to release anti-inflammation drugs depending on the occurrence of inflammation to regulate chronic inflammation is of high need. Here, we construct nanofiber-based scaffolds to regulate the inflammation response of chronic inflammation during tissue regeneration. An inflammation-sensitive prodrug is synthesized by free radical polymerization of the indomethacin-containing precursor, which is prepared by the esterification ofN-(2-hydroxyethyl) acrylamide with the anti-inflammation drug indomethacin. Then, anti-inflammation scaffolds are constructed by loading the prodrug in poly(ε-caprolactone)/gelatin electrospun nanofibers. Cholesterol esterase, mimicking the inflammation environment, is adopted to catalyze the hydrolysis of the ester bonds, both in the prodrug and the nanofibers matrix, leading to the generation of indomethacin and the subsequent release to the surrounding. In contrast, only a minor amount of the drug is released from the scaffold, just based on the mechanism of hydrolysis in the absence of cholesterol esterase. Furthermore, the inflammation-responsive nanofiber scaffold can effectively inhibit the cytokines secreted from RAW264.7 macrophage cells induced by lipopolysaccharide in vitro studies, highlighting the great potential of these electrospun nanofiber scaffolds to be applied for regulating the chronic inflammation in tissue regeneration.Keywords:enzyme-responsive drug release;anti-inflammatory;prodrug;electrospun nanofiber scaffold
研究领域:
药学
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生物材料
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组织工程
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Food Chemistry-X
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2022
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IF 6.443
Xiaoshan Long,Xiao Hu,Huan Xiang,Shengjun Chen,Laihao Li,Bo Qi,Chunsheng Li,Shucheng Liu,Xianqing Yang
This research aimed to analyze structural characterization and hypolipidemic activity in vitro of G. lemaneiformis polysaccharide (GLP) and its degradation products. The results presented that the content of galacturonic acid declined and glucuronic acid level enhanced, average particle size decreased from 99.9 μm to 25.7 μm, and color brightness of polysaccharide strengthened after degraded by H 2 O 2 -Vc. There was no significant change in thermal stability of polysaccharide before and after degradation. It was observed in AFM analysis, polysaccharide changed to smaller, delicacy and dispersion after degradation. As seen in FT-IR, H 2 O 2 -Vc degradation never change the structure of polysaccharide. Polysaccharide and its degradation products showed a significant inhibition effect on pancreatic lipase and cholesterol esterase in a dose-dependent manner, which presented the mixed type of competitive and non-competitive for pancreatic lipase, and non-competitive for cholesterol esterase, respectively. The fluorescence quenching type was static on pancreatic lipase and dynamic on cholesterol esterase.
研究领域:
海洋生物学
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生物化学
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药理学
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DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
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2020
·Vol. 20
·期 9
·2000116
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IF 3.416
Jingjing Ye,Xindan Zhang,Wenqi Xie,Min Gong,Meihong Liao,Qinghan Meng,Jiajia Xue,Rui Shi,Liqun Zhang
Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) for relieving inflammatory reactions can lead to severe side effects. It is of great importance to configure new dosing strategies for alleviating the side effects of NSAIDs. In this work, an enzyme-responsive anti-inflammatory prodrug capable of generating indomethacin upon the trigger of inflammation is developed. A monomer is first prepared after the esterification of carboxyl groups of indomethacin by hydroxyl groups of N -(2-hydroxyethyl) acrylamide. Then, a polymer prodrug, with indomethacin linked through ester bonds on the side chain, is synthesized by free radical polymerization of the monomer. The therapeutic drug component can be triggered to release from the prodrug under the stimulation of cholesterol esterase, mimicking the inflammation environment. On the contrary, there is only a small amount of drug released in the absence of the enzyme. Therefore, the drug can be triggered to release under the stimulation of an environment mimicking inflammation. Furthermore, the in vitro studies at the cellular level indicate that the enzyme-responsive prodrug can efficiently relieve inflammatory responses induced by lipopolysaccharide in RAW264.7 macrophage cells while indicating no cytotoxicity.
研究领域:
药理学
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药物递送系统
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炎症研究
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聚合物化学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2021
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IF 5.279
Xiangxin Li,Yijing Pu,Yan Xu,Jiankang Cao,Weibo Jiang
An in vitro intestinal model was used to evaluate the impact of banana condensed tannins (BCT) on the digestion of lipids (fat and cholesterol). BCT significantly suppressed the digestion of fat and cholesterol by interacting with digestive juice components. The interactions of BCT with a digestive juice mixture and its components (including bile acid, lipase, cholesterol esterase, CaCl2, NaCl, and cholesterol) were analyzed using turbidity, isothermal titration calorimetry, particle size distribution, zeta potential, and molecular docking analyses. The results showed that BCT reduced the digestion of lipids mainly via interaction with lipase, cholesterol esterase, bile acid, and cholesterol. Electrostatic CT–calcium ion complexes might reduce the extent of lipid digestion by decreasing the surface area of the lipid droplets exposed to the enzymes. This research provides valuable insights into the molecular mechanisms of the interaction of BCT with digestive juice components related to lipid digestion that may affect the rate and extent of lipid digestion.
研究领域:
营养学
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食品科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Animal Science and Biotechnology
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2022
·Vol. 13
·期 1
·1-13
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IF 6.175
Zhou Xiaoge,Mo Zhaoyi,Li Yankun,Huang Liang,Yu Sihai,Ge Lan,Hu Yamei,Shi Shengjie,Zhang Lutong,Wang Liguang,Gao Lei,Yang Gongshe,Chu Guiyan
Background Oleic acid is an abundant free fatty acid present in livestock that are in a negative energy-balance state, and it may have detrimental effects on female reproduction and fertility. Oleic acid induces lipid accumulation in bovine granulosa cells, which leads to a foam cell-like morphology and reduced steroidogenesis. However, why oleic acid increases lipid accumulation but decreases steroidogenesis remains unclear. This study focused on oleic acid’s effects on lipid type and steroidogenesis. Results Oleic acid increased the lipid accumulation in a concentration-dependent manner and mainly increased the triglyceride level and decreased the cholesterol ester level. Oleic acid also led to a decline in estradiol and progesterone production in porcine granulosa cells in vitro. In addition, oleic acid up-regulated the expression of CD36 and diacylglycerol acyltransferase 2, but down-regulated the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, scavenger receptor class B member 1 and acetyl-Coenzyme A acetyltransferase 2, as well as steroidogenesis-related genes, including cytochrome P450 family 11 subfamily A member 1, cytochrome P450 family 19 subfamily A member 1 and 3 as well as steroidogenic acute regulatory protein at the mRNA and protein levels. An oleic acid-rich diet also enhanced the triglyceride levels and reduced the cholesterol levels in ovarian tissues of female mice, which resulted in lower estradiol levels than in control-fed mice. Compared with the control, decreases in estrus days and the numbers of antral follicles and corpora lutea, as well as an increase in the numbers of the atretic follicles, were found in the oleic acid-fed female mice. Conclusions Oleic acid changed the lipid type stored in lipid droplets of ovarian granulosa cells, and led to a decrease in steroidogenesis. These results improve our understanding of fertility decline in livestock that are in a negative energy-balance state.
研究领域:
生殖生物学
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内分泌学
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动物科学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2023
·
IF 6
Yin Qin,You Luo,Shuyi Qiu,Qunying Zhang,Le Yang
Raspberry contains a broad array of valuable phytochemicals and therefore has positive effects on health. Fermentation can transform these components. The variations in the secondary metabolite profiles and bioactivities of red raspberry juice during Wickerhamomyces anomalus fermentation remain unknown. Herein, the effects of W. anomalus on the secondary metabolites, other constituents (total sugars, reducing sugars, and total acids) and bioactivities of raspberry juice were investigated. The fermentation significantly decreased the level of total sugars, reducing sugars, total acids and anthocyanins, but greatly increased the content of polyphenols and flavonoids. The antioxidant capacity and α-glucosidase inhibitory activity of raspberry juice were markedly enhanced after fermentation, whereas the cholesterol esterase inhibitory activity was reduced significantly. Moreover, 721 secondary metabolites were identified, wherein 437 secondary metabolites (240 upregulated, 197 downregulated) were selected as differential metabolites via targeted metabolomics. A total of 89 secondary metabolites were annotated in the Kyoto Encyclopedia of Genes and Genomes pathways, most of which were matched to biosynthesis of secondary metabolites and metabolic pathways. Phenolic acids were mainly transformed via phenylalanine metabolism and tyrosine metabolism. These results can provide reference for the development of functional raspberry beverages.
研究领域:
食品科学
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微生物学
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植物化学
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代谢组学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
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2024
·
IF 5
You Luo,Ruling Tang,Han Qiu,Angxin Song
Rosa roxburghii Tratt fruits (RRT) exhibit extremely high nutritional and medicinal properties due to its unique phytochemical composition. Probiotic fermentation is a common method for processing fruits. Variations in the non-volatile metabolites and bioactivities of RRT juice caused by different lactobacilli are not well understood. Therefore, we aimed to profile the non-volatile components and investigate the impacts of L. plantarum fermentation (LP) and L. paracasei fermentation (LC) on RRT juice (the control, CG). There were both similarities and differences in the effects of LP and LC on RRT juice. Both of the two strains significantly increased the content of total phenolic, total flavonoid, and some bioactive compounds such as 2-hydroxyisocaproic acid, hydroxytyrosol and indole-3-lactic acid in RRT juice. Interestingly, compared with L. paracasei , L. plantarum showed better ability to increase the content of total phenolic and these valuable compounds, as well as certain bioactivities. The antioxidant capacity and α-glucosidase inhibitory activity of RRT juice were notably enhanced after the fermentations, whereas its cholesterol esterase inhibitory activity was reduced significantly. Moreover, a total of 1466 metabolites were identified in the unfermented and fermented RRT juices. There were 278, 251 and 134 differential metabolites in LP vs CG, LC vs CG, LC vs LP, respectively, most of which were upregulated. The key differential metabolites were classified into amino acids and their derivatives, organic acids, nucleotides and their analogues, phenolic acids and alkaloids, which can serve as potential markers for authentication and discrimination between the unfermented and lactobacilli fermented RRT juice samples. The KEGG enrichment analysis uncovered that metabolic pathways, purine metabolism, nucleotide metabolism and ABC transporters contributed mainly to the formation of unique composition of fermented RRT juice. These results provide good coverage of the metabolome of RRT juice in both unfermented and fermented forms and also provide a reference for future research on the processing of RRT or other fruits.
研究领域:
食品科学
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代谢组学
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微生物学
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营养学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）