JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Shuhua Shan,Jiaqi Zhou,Ruopeng Yin,Lizhen Zhang,Jiangying Shi,Qinqin Qiao,Zhuoyu Li
Non-alcoholic fatty liver disease (NAFLD) is a serious health problem worldwide. Impeding fatty acid uptake may be an attractive therapeutic strategy for NAFLD. In the current study, we found that millet bran protein hydrolysate (MBPH) prepared by in vitro gastrointestinal bionic digestion exhibits the potential of anti-NAFLD in vitro and in vivo, characterized by the alleviation of hepatic steatosis and the reduction of lipid accumulation. Further, MBPH significantly decreased the expression levels of fatty acid uptake related genes (FABP1, FABP2, FABP4, CD36, and CPT-1α) of liver tissue in a NAFLD mice model through activating peroxisome proliferator-activated receptor γ (PPARγ) and efficiently restrained the fatty acid uptake of liver tissue, thus exerting anti-NAFLD activity. As expected, the anti-NAFLD effect induced by MBPH, characterized by the alleviation of hepatic vacuolar degeneration, hepatic steatosis, and fibrosis, was effectively abrogated with PPARγ inhibitor (GW9662) treatment. These results indicate that the retardant of fatty acid uptake induced by PPARγ activation may be the critical factor for the anti-NAFLD effect of MBPH. Collectively, MBPH has the potential as a next-generation dietary supplementation for the prevention and treatment of NAFLD.
研究领域:
营养学
·
药理学
·
肝病学
·
分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 6
·2908-2920
·
IF 6.1
Tongtong Che,Yukun Song,Wentao Su,Shanghua Xing,Haitao Wang,Mingqian Tan
Nonalcoholic fatty liver disease (NAFLD) is a metabolic syndrome disorder. Here, hepatic parenchymal cell and mitochondrial-targeted nanocarriers were constructed to deliver astaxanthin (AST) to liver tissue to maximize AST intervention efficiency. The hepatic parenchymal cell-targeting was achieved using galactose (Gal) conjugated onto whey protein isolate (WPI) through the Maillard reaction by recognizing asialoglycoprotein receptors specifically expressed in hepatocytes. Grafting triphenylphosphonium (TPP) onto glycosylated WPI by an amidation reaction enabled the nanocarriers (AST@TPP-WPI-Gal) to achieve dual targeting capability. The AST@TPP-WPI-Gal nanocarriers could target mitochondria in steatotic HepG2 cells with an enhanced anti-oxidative and anti-adipogenesis effect. The ability of AST@TPP-WPI-Gal to target liver tissue was verified by an NAFLD mice model, and the results showed that AST@TPP-WPI-Gal could regulate blood lipid disorders, protect liver function, and remarkably reduce liver lipid accumulation (40%) compared with that of free AST. Therefore, AST@TPP-WPI-Gal might have potential as a dual targeting hepatic agent for nutritional intervention for NAFLD.
研究领域:
药理学
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纳米技术
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肝病学
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营养科学
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代谢紊乱
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Shan Su,Xiaohong Liu,Min Zhu,Wen Liu,Jingyi Liu,Yujia Yuan,Fudong Fu,Zhiyong Rao,Jingping Liu,Yanrong Lu,Younan Chen
Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic lipid deposition, is one of the most prevalent chronic metabolic disorders globally, and its pharmaceutical treatments are still limited. Excessive lipid accumulation triggers endoplasmic reticulum (ER) stress and autophagy flux dysfunction, which are important mechanisms for NAFLD. Trehalose (Tre), a natural disaccharide, has been identified to reduce hepatic steatosis and glucose intolerance. However, its underlying mechanisms for NAFLD remain unclear. In this study, a high-fat-diet (HFD)-induced mouse NAFLD model and a saturated fatty acid palmitic acid (PA)-stimulated cell model were constructed. The results indicated that Tre supplementation ameliorated hepatocyte lipid deposition in vitro, as well as hepatic steatosis and hyperlipidemia in vivo. Mechanistically, Tre alleviated both autophagy flux dysfunction and endoplasmic reticulum (ER) stress. Under the stimulation of HFD or PA, Tre remarkably increased the expression and nucleic translocation of the lysosomal master protein transcription factor EB (TFEB), while decreasing the accumulation of p62 and also decreasing the ER stress markers (inositol-requiring enzyme 1 (IRE1α), XBP-1, CHOP, and BIP). Similar results were observed in an ER stressor tunicamycin (TM)-induced in vivo and in vitro models. In addition, the transcriptomic analysis of NAFLD patients revealed significant differences in ER stress-related and autophagy-related biomarkers, including TFEB, ATG7, IRE1α, and CHOP. Molecular docking results demonstrated a strong affinity between Tre and both IRE1α and TFEB. Overall, Tre protected hepatocytes from lipotoxicity-related ER stress and autophagy dysfunction, and its regulatory effect on the IRE1α–TFEB signaling pathway may be a critical mechanism. These findings suggest that Tre, as a bioactive substance with significant medicinal potential, holds considerable promise for drug development and clinical application in treating NAFLD.
研究领域:
药理学
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分子生物学
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代谢紊乱
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肝病学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yi Wu,Wen Yin,Ping Hao,Yueru Chen,Lingyun Yu,Xingjian Yu,Yu Wu,Xiaocong Li,Wenjia Wang,Hui Zhou,Yuan Yuan,Xiaoyu Quan,Yue Yu,Bing Hu,Shouhai Chen,Zhenlei Zhou,Wenjing Sun
In this study, a new polysaccharide (PSPJ) with specific molecular weight and monosaccharide compositions was isolated and purified from the water extract of Panacis Japonici Rhizoma (PJR). 16S rRNA analysis and untargeted metabolomic analysis were used to assess PSPJ's efficacy in averting non-alcoholic fatty liver disease (NAFLD). This study indicated that PSPJ significantly reduced liver fat accumulation , the increase in blood lipids and ALT caused by HFD, indicating that PSPJ can prevent NAFLD. We demonstrated through cell experiments that PSPJ does not directly affect liver cells. The gut microbiota disorder and alterations in short-chain fatty acids (SCFAs) induced by the high-fat diet (HFD) were ameliorated by PSPJ, as evidenced by the analysis of 16S rRNA. In particular, supplementing PSPJ reduced the abundance of Turicibacter , Dubosiella , and Staphylococcus , and increased the abundance of Bacteroides , Blautia , and Lactobacillus . Untargeted metabolomic analysis shows that PSPJ improves liver metabolic disorders by regulating arachidonic acid metabolism , carbohydrate digestion and absorption, fatty acid biosynthesis , fatty acid metabolism and retinol metabolism. The findings of our investigation indicate that PSPJ has the potential to modulate liver metabolism through alterations in the composition of intestinal bacteria, hence preventing NAFLD.
研究领域:
药理学
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代谢学
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微生物学
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胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2022
·
IF 5.168
Xueyun Liu,Man Hu,Chen Ye,Lihong Liao,Chang Ding,Lijuan Sun,Jichao Liang,Yong Chen
It is well known that the excessive accumulation of lipid in hepatocytes is one of the important causes of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to explore the effects of isosilybin on lipid metabolism in free fatty acids (FFAs) or TO901317-induced HepG2 cells. Cells were treated with FFAs (oleic acid: palmitic acid , 2:1) or TO901317 to induce steatosis in vitro. Intracellular triglyceride (TG) content was quantified using commercial assay kits. The mRNA and protein expression of genes involved in fatty acid uptake, synthesis and oxidation were analyzed by RT-qPCR and western blotting . Selected biological pathways regulated by isosilybin treatment were determined by GO and KEGG analysis. The results showed that isosilybin significantly reduced TG levels in FFAs- and TO901317-induced HepG2 cells. Further studies showed that isosilybin treatment decreased the mRNA and protein expression of lipid synthesis genes Srebp-1c, Pnpla3, Acc and Fas , as well as the mRNA expression of fatty acid uptake gene CD36, whereas increased the mRNA levels of lipid oxidation genes Pparα, Acox1 and Cpt1α, as well as the mRNA expression of lipid export gene Mttp, in FFAs-induced HepG2 cells. Moreover, TO901317 was employed to induce endogenous lipid synthesis and steatosis, and the expression of Srebp-1c and its target genes in TO901317-induced hepatocytes was basically similar to that in FFAs-induced hepatocytes following isosilybin treatment. We also observed the increased level of phosphorylated AMP kinase (AMPK) after isosilybin treatment, while this effect was reversed after further treatment with AMPK inhibitor , compound C. The results of GO and KEGG analysis indicated that the pathways of fatty acid and TG metabolism were regulated by isosilybin. Interestingly, we found that treatment with the diastereoisomer A of isosilybin increased TG level, while exposure to the diastereoisomer B of isosilybin decreased TG level in FFAs-induced HepG2 cells. The above results suggest that isosilybin can inhibit lipid synthesis and activate lipid oxidation through AMPK signaling pathway, thereby improving steatosis of hepatocytes, and isosilybin B is the basis of its active substance.
研究领域:
分子生物学
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细胞生物学
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药理学
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代谢紊乱
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Weihong Jing,Mingyue Jiang,Xiaoxue Fu,Jiaxin Yang,Lu Chen,Feng Leng,Ping Xu,Wenyan Huang,Chao Yu,Zhangyou Yang
Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease closely related to obesity, which has become a global health problem. However, current pharmacological therapies for NAFLD are limited by potential side effects, low effectiveness and poor aqueous solubility. Herein, we designed functionalized drug-albumin nanocomposites ( [email protected] NPs), which were prepared by self-assembly of the anti-obesity small-molecule drug (BAM15) and bovine serum albumin (BSA), for treatment of NAFLD. The proposed [email protected] NPs not only improve aqueous solubility and half-life of BAM15 but also exhibit hepatic-targeted capacity and an increased therapeutic efficacy. In vitro experiments revealed that [email protected] NPs possessed excellent biocompatibility, and improved resistance to adipogenesis and reduced lipid accumulation in human hepatocellular carcinoma cells. In vivo , [email protected] NPs showed liver targeting ability and powerful anti-obesity effects without altering body temperature or affecting food intake, and could effectively alleviate hepatic steatosis and improve therapeutic efficacy for NAFLD treatment. The above findings demonstrated that [email protected] NPs potentially served as a safe and effective drug for NAFLD treatment.
研究领域:
药理学
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纳米技术
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肝病学
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代谢疾病
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Xiang Li,Rongxia Li,Xueyu Wang,Xinying Zhang,Zhiyi Xiao,Haibo Wang,Wenhui Sun,Hao Yang,Peng Yu,Qing Hu,Qinghui Guo,Hua Sun
As a popular healthy tea beverage, Jinsi Huangju has been consumed in China for hundreds of years. However, its active ingredients which dissolved in hot water have not been fully determined. In this study, 14 compounds were identified by different spectroscopic techniques , including 11 compounds identified in this plant for the first time. For in-depth studies, apigenin-7- O -6″-malonylglucoside ( 8 ) and luteolin-7- O -6″-malonylglucoside ( 9 ) were synthesized for the first time by 5 steps in 1.2% overall yields. Further analyses of the natural compounds showed that 8 could inhibit pancreatic lipase , reduce cellular lipid contents, and attenuate insulin resistance in vitro . Furthermore, 8 restore lipid and inflammatory profiles in the plasma and liver (TG, TC , ALT , AST , LDL-C, HDL-C, MPO , and IL-6) and attenuated hepatic steatosis in NAFLD mouse models. In conclusion, Jinsi Huangju and its active ingredients are candidates for developing drug, functional foods and therapeutic strategies for hyperlipidaemia and NAFLD.
研究领域:
药理学
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生物化学
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营养学
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肝病学
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植物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2019
·
IF 7.901
Wendi Teng,Liyun Zhao,Songtao Yang,Chengying Zhang,Meiyu Liu,Jie Luo,Junhua Jin,Ming Zhang,Chen Bao,Dan Li,Wei Xiong,Yuan Li,Fazheng Ren
Nonalcoholic fatty liver disease (NAFLD) is the early stage of many metabolic syndromes . The intervention of NAFLD can prevent its further development into severe metabolic syndromes. Given the inefficiency and side effects of chemical drugs for treating NAFLD, the hepatic-targeted nanocarriers loaded with bioactive compounds may offer a more effective and acceptable strategy for eliminating NAFLD. Here we developed hepatic-targeted oxidized starch-lysozyme (OSL) nanocarriers to specifically deliver resveratrol (Res) to liver tissue in order to maximize its therapeutic efficiency. The hepatic targeting was achieved using covalently conjugated galactose (Gal), which is recognized by the asialoglycoprotein receptors specifically expressed in hepatocytes. In steatotic HepG2 cell model, treatment with hepatic-targeted Gal-OSL/Res nanocarriers enhanced the cellular Res uptake and anti-lipogenesis capabilities, and effectively decreased triglyceride accumulation by modulating AMP-activated protein kinase (AMPK)/silent information regulation 2 homolog 1(SIRT1)/fatty acid synthase (FAS)/sterol regulatory element-binding protein-1c (SREBP1c) signaling pathway. In mice, Gal-OSL increased Res delivery into liver tissues and increased their hepatic effective concentration in liver. Most importantly, Gal-OSL/Res nanocarriers effectively reversed NAFLD and recovered hepatic insulin sensitivity of NAFLD mice to the healthy state. Furthermore, Gal-OSL/Res efficiently ameliorated lipid deposition and insulin resistance by modulating AMPK/SIRT1/FAS/SREBP1c signaling pathway and downregulated insulin receptor substrate-1 (IRS-1) phosphorylation at serine 307 in liver. These findings suggested that the hepatic-targeted Gal-OSL nanocarriers delivering Res could potentially serve as a safe and promising platform for NAFLD and other liver related diseases.
研究领域:
药学
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纳米技术
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肝病学
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代谢性疾病
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2022
·Vol. 103
·期 4
·2196-2206
·
IF 4.125
Chenjing Li,Yihua Feng,Jingyao Li,Rui Lian,Liehao Qin,Chunling Wang
BACKGROUND Purple sweet potato Ipomoea batatas (L.) has long been used as a medicine and a food. It contains various bioactive substances such as polysaccharides, anthocyanins, and flavonoids. Purple sweet potato polysaccharides are known to have anti-oxidant, anti-tumor, and immunomodulatory functions. Nevertheless, studies on the structural characterization of purple sweet potato polysaccharides and their ability to prevent non-alcoholic fatty liver disease (NAFLD) have rarely been reported. RESULTS A novel polysaccharide (PSPP-A) was extracted and isolated from purple sweet potato, and its structural characteristics and preventive effects on NAFLD were investigated. The results indicated that PSPP-A was composed of l -rhamnose, d -arabinose, d -galactose, d -glucose, and d -glucuronic acid with molar ratios of 1.89:8.45:1.95:1.13:1. Its molecular weight was 2.63 × 10 3 kDa. Methylation and nuclear magnetic resonance (NMR) analysis indicated that the glycosidic linkages were →3)- α -L-Ara f -(1→, α -L-Ara f -(1→, →2,4)- α -L-Rha p -(1→, 4-O-Me- β -D-GlcA p -(1→, →4)- α -D-Glc p -(1→, →4)- β -D-Gal p -(1→, and →6)- β -D-Gal p -(1→. Scanning electron microscopy (SEM) indicated that the structure of PSPP-A was irregular. Subsequently, the protective effect of PSPP-A on NAFLD was investigated. The results indicated that bodyweight, liver index, and triglyceride (TG), total cholesterol (TC), aspartate transaminase (AST), and alanine transaminase (ALT) content were significantly reduced by intervention of purple sweet potato polysaccharide-A (PSPP-A) compared with the - high-fat diet group. Liver histopathological analysis indicated that PSPP-A attenuated irregular hepatocyte patterns and excessive lipid vacuoles. CONCLUSIONS The novel polysaccharide, PSPP-A, mainly contains arabinose, which has certain preventive effects on NAFLD. This study provides a theoretical basis for further elucidating the hepatoprotective effect of purple sweet potatoes as a functional food. © 2022 Society of Chemical Industry.
研究领域:
食品科学
·
药理学
·
生物化学
·
营养学
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医学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 10
·3709-3725
·
IF 6.6
Xiaofei Xin,Jingjing Li,Wantao Wu,Pengbo Zhao,Yang Yang,Ying Zhu,Lianjie Ren,Chao Qin,Lifang Yin
Non-alcoholic fatty liver disease (NAFLD) is a chronic inflammatory disease characterized by “multiple crosstalk” paths of insulin resistance, lipid metabolism, oxidative stress, etc. The combination of LY294002 and oridonin was proposed as a promising therapy by targeting insulin–PI3K/AKT signaling and NF-κB inflammatory pathway. However, due to oxidative stress, disease-associated upregulation of murine CYP3A11 activity can contribute to unexpected drug metabolism and disposition, which could seriously hinder the efficacy of LY294002 and oridonin. Nanotechnology-based effective reactive oxygen species (ROS) scavengers have emerged as a promising strategy to overcome these limitations. In this study, a rationally designed ROS-responsive liposome loaded with oridonin and LY294002 (RLLs) was developed for effective liver deposition and metabolic regulation for NAFLD treatment. First, we ascertained that the insulin resistance-induced signaling response was balanced by the combination of LY294002 and oridonin. Then, the particle size, zeta potential, ROS-responsive release behavior, and ROS-scavenging properties were investigated. Moreover, the CCl4-exposed mouse model was used to assess the biodistribution and therapeutic efficacy of RLLs on NAFLD. Finally, the “multiple crosstalk” modulation of RLLs was explored by western blotting, enzyme-linked immunosorbent assay, and polymerase chain reaction analysis. RLLs exhibited antioxidant efficacy for the safe delivery of LY294002 and oridonin with good stability and biocompatibility. The biodistribution analysis proved that the accumulation of RLLs was significantly increased due to CD44-mediated targeting. In addition, RLLs had comprehensive protective effects on the CCl4-exposed mouse model, leading to significant elimination of excessive ROS, maintenance of insulin sensitivity and CYP450 activity, and reduction of inflammatory response. In the CCl4-induced mice, RLL intervention remarkably improved metabolic profiles and reduced the fibrosis lesions. Our results provided a strategy for the amelioration of oxidative stress and CYP450 activity using ROS-responsive thioketal as an antioxidant adjuvant facilitated by nanotechnology.
研究领域:
药理学
·
纳米技术
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Sa Yang,Shijie Cao,Congyu Li,Jichao Zhang,Chang Liu,Feng Qiu,Ning Kang
Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. Berberine (BBR) is an effective therapeutic agent in alleviating NAFLD. Berberrubine (BRB) is one of the main active metabolites of BBR, which shows significant anti-obesity and antihypoglycemic effects. However, whether BRB is responsible for the in vivo therapeutic effect and the underlying mechanism of BRB on NAFLD have not been elucidated. In this study, the ability of BRB to ameliorate NAFLD, together with its molecular mechanism, was investigated. The results showed that BRB treatments could significantly improve hepatic steatosis and insulin resistance in high-fat diet (HFD)-fed mice and oleic acid (OA)-treated HepG2 cells. Meanwhile, BBR and BRB treatment similarly prevented lipid accumulation by regulating the protein expression of ATGL, GK, PPARα, CPT-1, ACC1, FAS, and CD36. In addition, compared with BBR, BRB could maintain glucose homeostasis via GLUT2, GSK3β, and G6Pase in HFD-fed mice. Furthermore, the components of the gut microbiota in mice were analyzed by 16S rRNA gene sequencing. BBR and BRB treatment could greatly modify the structure and composition of gut microbiota. At the genus level, BBR and BRB treatment decreased Lactobacillus and Romboutsia , while BBR increased beneficial bacteria, such as Akkermansia and Bacteroides , and BRB increased beneficial bacteria, such as Ileibacterium and Mucispirillum . Altogether, both BRB and BBR were active in alleviating NAFLD in vivo and BRB might be used as a functional material to treat NAFLD clinically.
研究领域:
药理学
·
代谢学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2024
·
IF 5.6
Lan Li,Shengye Yang,Xinyu Liang,Yameng Liu,Hualing Xu,Xiaozhen Guo,Cen Xie,Xiaojun Xu
Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease worldwide. Bupleurum is widely used in the treatment of non-alcoholic fatty liver, and saikosaponin D (SSD) is one of the main active components of Bupleurum. The purpose of this study was to investigate the efficacy of SSD in the treatment of NAFLD and to explore the mechanism of SSD in the improvement of NAFLD based on “gut-liver axis”. Our results showed that SSD dose-dependently alleviated high fat diet-induced weight gain in mice, improved insulin sensitivity, and also reduced liver lipid accumulation and injury-related biomarkers aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Further exploration found that SSD inhibited the mRNA expression levels of farnesoid X receptor ( Fxr ), small heterodimer partner ( Shp ), recombinant fibroblast growth factor 15 ( Fgf15 ) and apical sodium dependent bile acid transporter ( Asbt ) in the intestine, suggesting that SSD improved liver lipid metabolism by inhibiting intestinal FXR signaling. SSD can significantly reduce the gut microbiota associated with bile salt hydrolase (BSH) expression, such as Clostridium . Decreased BSH expression reduced the ratio of unconjugated to conjugated bile acids, thereby inhibiting the intestinal FXR. These data demonstrated that SSD ameliorated NAFLD potentially through the gut microbiota-bile acid-intestinal FXR pathway and suggested that SSD is a promising therapeutic agent for the treatment of NAFLD.
研究领域:
药理学
·
胃肠病学
·
微生物学
·
代谢学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）