Nutrients
·
2018
·Vol. 10
·期 7
·855
·
IF 4.196
Mohammad Hosein Farzaei,Mahdi Zobeiri,Fatemeh Parvizi,Fardous F. El-Senduny,Ilias Marmouzi,Ericsson Coy-Barrera,Rozita Naseri,Seyed Mohammad Nabavi,Roja Rahimi,Mohammad Abdollahi
Oxidative stress has been considered a key causing factor of liver damage induced by a variety of agents, including alcohol, drugs, viral infections, environmental pollutants and dietary components, which in turn results in progression of liver injury, non-alcoholic steatohepatitis, non-alcoholic liver disease, liver fibrosis and cirrhosis. During the past 30 years and even after the major progress in the liver disease management, millions of people worldwide still suffer from an acute or chronic liver condition. Curcumin is one of the most commonly used indigenous molecules endowed by various shielding functionalities that protects the liver. The aim of the present study is to comprehensively review pharmacological effects and molecular mechanisms, as well as clinical evidence, of curcumin as a lead compound in the prevention and treatment of oxidative associated liver diseases. For this purpose, electronic databases including “Scopus,” “PubMed,” “Science Direct” and “Cochrane library” were extensively searched with the keywords “curcumin or curcuminoids” and “hepatoprotective or hepatotoxicity or liver” along with “oxidative or oxidant.” Results showed that curcumin exerts remarkable protective and therapeutic effects of oxidative associated liver diseases through various cellular and molecular mechanisms. Those mechanisms include suppressing the proinflammatory cytokines, lipid perodixation products, PI3K/Akt and hepatic stellate cells activation, as well as ameliorating cellular responses to oxidative stress such as the expression of Nrf2, SOD, CAT, GSH, GPx and GR. Taking together, curcumin itself acts as a free radical scavenger over the activity of different kinds of ROS via its phenolic, β-diketone and methoxy group. Further clinical studies are still needed in order to recognize the structure-activity relationships and molecular mechanisms of curcumin in oxidative associated liver diseases.Keywords:curcumin;hepatotoxicity;liver diseases;oxidative stress;systematic review
研究领域:
医学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Cell Discovery
·
2024
·Vol. 10
·期 1
·1-7
·
IF 13
Li Yang,Chen Zhi-Peng,Xu Da,Wang Liang,Cheng Meng-Ting,Zhou Cong-Zhao,Chen Yuxing,Hou Wen-Tao
Human ABC transporters ABCD1–3 are all localized on the peroxisomal membrane and participate in the β-oxidation of fatty acyl-CoAs, but they differ from each other in substrate specificity. The transport of branched-chain fatty acids from cytosol to peroxisome is specifically driven by ABCD3, dysfunction of which causes severe liver diseases such as hepatosplenomegaly. Here we report two cryogenic electron microscopy (cryo-EM) structures of ABCD3 bound to phytanoyl-CoA and ATP at resolutions of 2.9 Å and 3.2 Å, respectively. A pair of phytanoyl-CoA molecules were observed in ABCD3, each binding to one transmembrane domain (TMD), which is distinct from our previously reported structure of ABCD1, where each fatty acyl-CoA molecule strongly crosslinks two TMDs. Upon ATP binding, ABCD3 exhibits a conformation that is open towards the peroxisomal matrix, leaving two extra densities corresponding to two CoA molecules deeply embedded in the translocation cavity. Structural analysis combined with substrate-stimulated ATPase activity assays indicated that the present structures might represent two states of ABCD3 in the transport cycle. These findings advance our understanding of fatty acid oxidation and the molecular pathology of related diseases.
研究领域:
生物化学
·
分子生物学
·
医学遗传学
✓ 已验证
DOI
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Shaofei Song,Hong Peng,Yuan Li,Tingting Zhao,Renjie Cao,Lei Zheng,Min Huang,Yiming Jiang
Liver regeneration after liver tumor resection or liver transplantation is crucial, the remaining liver frequently fails to regenerate in some patients. Oleanolic acid (OA), a pentacyclic triterpenoid compound which has been shown to protect against various liver diseases. However, the effect of OA on liver regeneration after partial hepatectomy (PHx) is still unclear. In this study, the results showed that OA (50 mg/kg, twice daily) treatment induced liver mass restoration and increased the liver-to-body weight ratio of mice following PHx. Meanwhile, OA promoted hepatocyte proliferation and increased the number of BrdU-, Ki67-and PCNA-positive cells. Furthermore, OA increased the nuclear accumulation of PXR and induced the expression of PXR downstream proteins such as CYP3A11, UGT1A1 and GSTM2 in mice, as well as in AML12 and HepRG cells. Luciferase reporter assay and nuclear localization of PXR further demonstrated the effect of OA on PXR activation in vitro . Molecular docking simulation showed that OA could interact with the PXR active sites. Moreover, OA inhibited the expression of FOXO1, RBL2 and CDKN1B, and increased the expression of PCNA, CCND1 and CCNE1 in vivo and in vitro . Silencing of Pxr further confirmed that OA-mediated upregulation of proliferation-related proteins depended on PXR. The current study illustrated that OA exhibited a significant promoting effect on liver regeneration following PHx, potentially through regulation of the PXR signaling pathway to accelerate liver recovery.
研究领域:
药理学
·
肝脏病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Changhong Yuan,Wenwen Fan,Tengfei Zhou,Dianjun Sun,Hongzhuo Liu,Zhonggui He,Yongjun Wang
Ursolic acid (UA), a natural pentacyclic terpenoid carboxylic acid that can exert a potent hepatoprotective activity, has been developed into various types of nanoparticles to improve its pharmacological effects, however, the phagocytosis of nanoparticles by Kupffer cells greatly limits its efficacy. Herein, UA/Tween 80 nanovesicles (V-UA) were constructed and despite its simple composition, it fulfills multiple functions simultaneously: UA served as not only an active ingredient in the nanovesicle drug delivery system , but also acts as part of the carrier to stabilize UA/Tween 80 nanostructure ; with a molar ratio of UA to Tween 80 up to 2:1, the formulation possesses a significant advantage of higher drug loading capacity; relative to liposomal UA (Lipo-UA), a conditional cellular uptake and higher accumulation of V-UA in hepatocytes provide insights into the hepatocytes targeting mechanisms of this nanovesicles. Favorable hepatocyte targeting ability also facilitates the treatment of liver diseases, which was well validated in three liver disease models.
研究领域:
药学
·
纳米技术
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Feilin Wang,Yi Liu,Peijian Cai,Xin Zhong,Jinhong Zhong,Yufu Li,Huizhong Hu,Yuanhao Sheng,Haihui Pan,Fansheng Kong
Luteolin (Lut) is a natural flavonoid that has been widely used in the treatment of liver and glycolipid metabolic diseases. However, poor water solubility and bioavailability limit its efficacy and application. To overcome these challenges, a protein–polysaccharide composite nanoparticle (L-GF NPs) for Lut delivery was prepared by a self-assembly method based on amphiphilic gelatin and active finger citron polysaccharide (FCP). The L-GF NPs were approximately spherical in shape and were formed by hydrogen bonding, electrostatic interaction, and hydrophobic interaction. Lut was encapsulated in the nanoparticles in an amorphous state, and the encapsulating efficiency was 79.49%. The efficacy of L-GF NPs was evaluated by intragastric administration of an alcoholic liver disease (ALD) mouse model. L-GF NPs have been demonstrated to significantly ameliorate the symptoms of ALD mice, which are mainly achieved by reducing lipid accumulation and oxidative stress and inhibiting the NF-κB pathway. In conclusion, the aqueous solubility and bioavailability of Lut were markedly enhanced by FCP encapsulation. Meanwhile, the combined effect of Lut and FCP significantly ameliorated ALD and attenuated alcohol-induced lipid metabolic disorders and oxidative damage. This provides a new strategy to promote the prevention and treatment of ALD.
研究领域:
药剂学
·
肝脏疾病
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2021
·Vol. 11
·期 10
·2023-2029
·
IF 0.287
Zhang Wang,Zhou Yujun,Xu Xiuli,Tian Yaping,Zhang Chunyan
Liver disease is a great danger to human health. The determination of blood level of Cholyglycine acid (CG) is a vital biomarker for the assessment of liver function in clinic, which is contribute to the diagnosis of liver diseases. Thus, establishing accuracy, rapid and convenient
method for the detection of glycolic acid is of great significance. In this study, a time-resolved-fluorescence (TRF) lateral flow assay for rapid detection of CG was development. The analytical detection limit (mean of zero-2 SD) was 0.06 μg/mL The method showed good linearity in
the range of 0.2–40 g/mL and was not affected by biomolecules with similar structure to CG. The analytical mean recovery of control was between 90–110% and the imprecision of intra- and inter-assay of CVs was less than 10%. No significant matrix effect was observed in saline, serum,
plasma or whole blood. A good correlation was found with the homogeneous enzyme immunoassay (HEIA) assay (slopes 1.0463, y-intercepts 0.2721 μg/mL, R = 0.989, n = 50, P < 0.001). The CG TRF analysis could provide reproducible and quantitative information
about the state of liver in a few minutes, which is suitable for the detection of liver diseases in point-of-care-testing (POCT) conditions.
研究领域:
医学检验
·
肝脏疾病
·
临床诊断
✓ 已验证
DOI
高影响因子
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2024
·Vol. 27
·期 5
·773-785
·
IF 1.6
Liu Kejia,Yang Xu,Zhang Guihong,Xiang Zheng
Background: Fuzi-Gancao herb couple is one of the most common herb couples involved in the TCM formula, which was used for the treatment of chronic diseases. The herb couple has a hepatoprotective effect. However, its main components and therapeutic mechanism are not yet clear. This
study aims to elucidate the therapeutic effect and mechanism of the Fuzi-Gancao herb couple on NAFLD from animal experiments, network pharmacology, and molecular docking. Methods: 60 Male C57BL/6 mice (20 g ± 2 g) were randomly divided into six groups including the blank group
(n=10) and NALFD group (n=50). The mice of the NALFD group were fed with a high-fat diet for 20 weeks to establish the NAFLD model and the NALFD mice were randomly divided into five groups including positive group (berberine), model group and F-G groups with three dosages (0.257, 0.514, 0.771
g/kg) (n=10). After 10 weeks of administration, the serum was collected for the analysis of ALT, AST, LDL-c, HDL-c, and TC, and liver tissues were collected for pathological analysis. The TCMAS database was used to collect the main components and targets of the Fuzi-Gancao herb couple. The
GeneCards database was used to collect NAFLD-related targets, and the key targets were obtained by intersecting with herbal targets. The diseasecomponent- target relationship diagram was constructed by Cytoscape 3.9.1. The obtained key targets were imported into the String database to obtain
the PPI network, and imported into the DAVID database for KEGG pathway analysis and GO analysis. Finally, the key targets and key gene proteins were imported into Discovery Studio 2019 for molecular docking verification. Results: In this study, H-E staining indicated the pathological
changes of liver tissue in Fuzi- Gancao groups were significantly improved, and the levels of AST, ALT, TC, HDL-c, and LDL-c in serum of Fuzi-Gancao groups decreased in a dose-dependent manner, compared with the model group. 103 active components and 299 targets in the Fuzi-Gancao herb couple
were confirmed in the TCMSP database and 2062 disease targets in NAFLD were obtained. 142 key targets and 167 signal pathways were screened, such as the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and so on.
The main bioactive ingredients of Fuzi-Gancao herb couple in the treatment of NAFLD are quercetin, kaempferol, naringenin, inermine, (R)-norcoclaurine, isorhamnetin, ignavine, 2,7-Dideacetyl-2,7- dibenzoyl-taxayunnanine F, glycyrol mainly involving IL6, AKT1, TNF, TP53, IL1B, VEGFA and other
core targets. Molecular docking analysis indicated that there is a good affinity between the key components and the key targets. Conclusion: This study preliminarily explained the main components and mechanism of the Fuzi- Gancao herb couple in the treatment of NAFLD and provided an idea
for subsequent research.
研究领域:
中药学
·
肝脏疾病
·
生物信息学
✓ 已验证
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 27
·13249-13259
·
IF 3.925
Changning Xue,Lifen Zhang,Yuman Zhang,Yao Yu,Chenlu Xu,Zhi Li
Nonalcoholic fatty liver disease (NAFLD) is a typical metabolic disease caused by excessive accumulation of lipid in the liver. Lovastatin (Lov) is a representative of a classic lipid-lowering drug, but the drug has a lack of targeting, and the toxic and side effects are serious. Reactive oxygen species (ROS), which can lead to a “second strike” of NAFLD, eventually lead to cirrhosis and hepatic cancer. Therefore, a H2O2-responsive and self-fluorescence prodrug-nanosystem (PBI-Lov) has successfully been constructed. While consuming ROS and leading to breaking of the oxalate bond, it will result in the release of lovastatin. Negatively charged phosphatidylserine (PS) was coated on PBI-Lov to prepare PS-PBI-Lov nanoparticles. The uptake of PS-PBI-Lov nanoparticles could be increased both in HepG2 cells and RAW264 7 cells. Most importantly, these fluorescence nanoparticles realized rapid, real-time and high-precision detection in tetracycline mice. PS-PBI-Lov nanoparticles effectively targeted the liver, and decreased both lipid accumulation and vacuole structures in the liver, reducing the degree of fibrosis, and effectively reversing the NAFLD.
研究领域:
药理学
·
纳米技术
·
肝脏疾病
·
代谢紊乱
·
药物递送系统
✓ 已验证
DOI
高影响因子
Probiotics and Antimicrobial Proteins
·
2018
·Vol. 11
·期 1
·175-185
·
IF 2.345
Liang Yinji,Liang Shu,Zhang Yupei,Deng Yuanjun,He Yifang,Chen Yanning,Liu Chan,Lin Chenli,Yang Qinhe
The aim of this study was to investigate how the effects of compound probiotics modulate the gut microbiota, short-chain fatty acid (SCFA), body composition, serum and liver lipids, and inflammatory markers in non-alcoholic fatty liver disease (NAFLD) rats. Twenty-four male SD rats were randomly divided into 3 groups: normal control group (standard feed), high-fat diet (HFD) feeding group (83% standard feed + 10% lard oil + 1.5% cholesterol + 0.5% cholate + 5% sucrose), and compound probiotics intervention group (HFD + 0.6 g × kg −1 × d −1 compound probiotics). The microbial population was assessed by 16S rDNA amplification and sequence analysis. Body composition, serum and liver lipids, serum inflammatory markers, colonic SCFAs, and relative proteins were assessed. The results showed that compound probiotics significantly reduced body weight, visceral and total fat mass, and the levels of hepatic TC and TG and serum TG, FFA, ALT, LPS, IL-1β, and IL-18 ( P < 0.05). The proportions of TM7 phylum (0.06 vs 1.57%, P < 0.05) clearly increased, while that of Verrucomicrobia phylum (5.69 vs 2.61%, P < 0.05) clearly decreased. Compound probiotics also increased the representation of Ruminococcus genus (0.95 vs 1.83%, P < 0.05), while the proportion of Veillonella genus decreased (0.10 vs 0.03%, P < 0.05). The levels of colonic SCFAs and GPR43, NLRP3, ASC, and CASPASE-1 proteins also changed significantly ( P < 0.05). Compound probiotics modulated gut microbiota, SCFAs, and their receptor GPR43 in NAFLD rats. These changes might inhibit lipid deposition and chronic metabolic inflammation in response to the insult of HFD.
研究领域:
微生物学
·
营养学
·
分子生物学
·
代谢学
·
肝脏疾病
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2018
·Vol. 233
·期 9
·6996-7006
·
IF 3.923
Tingting Xia,Runze Zhao,Wanqian Liu,Qiping Huang,Peixing Chen,Yasinta N. Waju,Mohanad K. Al-ani,Yonggang Lv,Li Yang
Hepatic fibrosis progress accompanied by an unbalanced extracellular matrix (ECM) degradation and deposition leads to an increased tissue stiffness. Hepatocytes interplay with all intrahepatic cell populations inside the liver. However, how hepatocytes migration and cellular Young's modulus influenced by the substrate stiffness are not well understood. Here, we established a stiffness-controllable in vitro cell culture model by using a polyvinyl alcohol (PVA) hydrogel that mimicked the same physical stiffness as a fibrotic liver. Three levels of stiffness were used in our experiment that corresponded to the stiffness levels found in normal liver tissue (4.5 kPa), the early (19 kPa) and late stages (37 kPa) of fibrotic liver tissues. Cytoskeleton of hepatocyte was influenced by substrate stiffness. Soft substrate promoted the cellular migration and directionality. The cellular Young's modulus firstly increased and then decreased with increasing substrate stiffness. Integrin-β1 and β-catenin expression on cytomembrane were up-regulated and down-regulated with the increase of substrate stiffness, respectively. Our data not only suggested that hepatocytes were sensitive to substrate stiffness, but also suggested that there may be a potential relationship among substrate stiffness, cellular Young's modulus and the dynamic balance of integrin-β1 and β-catenin pathways. These results may provide us a new insight in mechanism investigation of mechano-dependent diseases, especially like fibrosis related diseases.
研究领域:
细胞生物学
·
生物力学
·
肝脏疾病
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Jiabin Zhang,Xiaodie Chen,Yurong Chai,Yuanyuan Jin,Fenfang Li,Chenya Zhuo,Yanteng Xu,Haixia Wang,Enguo Ju,Yeh-Hsing Lao,Xi Xie,Mingqiang Li,Yu Tao
Acute liver failure (ALF) is a highly lethal condition characterized by massive tissue necrosis, excessive oxidative stress, and serious inflammatory storms, necessitating prompt medical intervention. Although hepatocyte-like cells (HLCs) derived from mesenchymal stromal/stem cells (MSCs) offer a promising alternative cell source for hepatocyte therapy, their low in-vivo integration and differentiation efficiency may compromise the eventual therapeutic efficacy. To this end, MSCs are bioengineered into multicellular spheroids in the present study. The proteomic analyses and experimental results reveal that extracellular vesicles (EVs) derived from these MSC spheroids (SpEV) contain abundant highly expressed bioactive proteins and can be efficiently endocytosed by recipient cells, resulting in enhanced pro-angiogenic and antioxidative effects. In addition, MSC spheroids exhibit superior hepatic cell differentiation compared to an equivalent number of dissociated single MSCs, particularly when being co-cultured with hexagonally patterned endothelial cells in a liver lobule-like arrangement. Following orthotopic implantation in the mouse model, the enhanced paracrine effects of SpEV, combined with an immunoregulatory decellularized extracellular matrix hydrogel carrier and functional artificial liver lobules (ALL), synergically contribute to the effective amelioration of ALF, highlighting the substantial potential for clinical translation.
研究领域:
再生医学
·
肝脏疾病
·
生物工程
·
细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Meng Sun,Min Li,Min Hu,Yueyun Fan,Yanhong Liu,Jian Sun,Jinfeng Zhang
Acute liver failure (ALF) is a serious global disease characterized by rapid onset and high mortality. Currently, the clinical treatment of ALF faces considerable hurdles due to limited medication options and the scarcity of liver transplants. Despite biomacromolecules such as hepatocyte growth factor (HGF) and glutathione (GSH) having been applied for ALF symptom relief in the clinic, they still face substantial challenges including poor stability, difficulty in acting on intracellular targets, and inadequate therapeutic outcome. In this work, by taking advantage of the innate targeting and regenerative capabilities of mesenchymal stem cells (MSCs), we harnessed MSC-derived exosomes as natural bioactive carriers for the simultaneous delivery of HGF and GSH, forming a fully bioactive nanodrug termed HG@Exo. Impressively, the HG@Exo demonstrated potent therapeutic effects against both carbon tetrachloride (CCl4)- and extreme hepatectomy-induced ALF through multiple mechanisms, including regulation of oxidative stress, reduction of inflammation, and promotion of hepatocyte regeneration, which were facilitated by its inflammation-targeting to damaged liver tissues. Furthermore, an FDA-approved near-infrared fluorescent dye, indocyanine green (ICG), has been incorporated into the exosomes (HGI@Exo) to endow them with real-time in vivo tracking capability, which showed favorable liver accumulation of the HGI@Exo in both CCl4- and surgery-induced ALF animal models, providing crucial insights into their biodistribution and therapeutic efficacy. Overall, the presented fully bioactive nanodrugs with targeting and theranostic abilities hold significant promise for potentiating the therapeutic efficacy of biomacromolecules for the improved treatment of ALF and other inflammatory diseases.
研究领域:
药理学
·
纳米医学
·
干细胞治疗
·
肝脏疾病
·
分子生物学
✓ 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）