JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2021
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IF 5.279
Shuhua Tian,Yunfan Wang,Xiangfei Li,Jie Liu,Jing Wang,Yingjian Lu
The most common complications of obesity are metabolic disorders such as nonalcoholic fatty liver disease (NAFLD), hyperglycemia, and low-grade inflammation. Sulforaphane (SFN) is a hydrolysate of glucosinolate (GLS) that is found in large quantities in cruciferous vegetables. The objective of this research was to evaluate the mechanism by which SFN relieves obesity complications in obese mice. C57BL/6J mice were fed a high-fat diet to induce obesity and treated daily with 10 mg/(kg body weight (bw)) SFN for 8 weeks, while a positive control group was treated daily with 300 mg/(kg bw) metformin. Our results indicated that SFN attenuated NAFLD, inflammation, oxidative stress, adipose tissue hypertrophy, and insulin resistance, as well as regulated glucose and lipid metabolism. SFN regulated glucose and lipid metabolism by deactivating c-Jun N-terminal kinase (JNK) and blocking the inhibitory effect of the insulin signaling pathway. SFN also regulated glucose metabolism by alleviating fibroblast growth factor 21 (FGF21) resistance. Our research provides an empirical basis for clinical treatment with SFN in obesity.
研究领域:
营养学
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代谢紊乱
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Ping Wu,Juan Zhao,Haowen Qiao,Kaihang Yu,Yanfang Zhao,Xiaolei Meng,Luyang Ye,Yunhao Cai,Xinwang Ying,Liuxi Chu,Junpeng Xu,Junqing Huang,Dawei Jiang,Qian Xu,Shengcun Li,Lizhu Yang,Lihua Luo,Sipin Zhu,Zhiqiang Luo,Qi Dong,Yingshan Zhou,Xiaokun Li,Zhouguang Wang
Ferroptosis-induced oxidative stress triggers mitochondrial damage in spinal cord injury (SCI), impairing residual neuronal function and driving microglial M1 polarization. Regulating neuronal mitochondrial function is an urgent problem in the field of tissue engineering. To address this, an injectable dual-network hyaluronic acid/black phosphorus (BP)/ fibroblast growth factor 21 (FGF21) composite hydrogel (ADBF) is explored, and the successful application of this functional hydrogel in SCI repair is demonstrated. The two-dimensional BP matrix enables high-efficiency loading of macromolecular drugs such as FGF21. Sustained FGF21 release from ADBF reduces neuronal oxidative stress and mitigates neurodegeneration. Subsequent exposure of BP nanosheet surfaces enhances cation adsorption (e.g., iron ions), thereby inhibiting ferroptosis. In a mouse model of SCI, behavioral, electrophysiology and immunohistochemistry investigations suggested that the composite ADBF hydrogels can effectively promote functional repair by enhancing remyelination, accelerating axonal regeneration, inhibiting neurons ferroptosis and regulating immune microenvironment of nerve regeneration. Mechanistically, ADBF attenuates ferroptosis by restoring mitochondrial function via the AMPK/AKT signaling axis, consequently promoting microglial M2 polarization. This strategy of integrating BP/FGF21 nanosheets into an injectable conductive hydrogel provides new insight into designing advanced anti-ferroptosis therapy biomaterials for SCI repair.
研究领域:
生物材料
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纳米医学
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神经工程
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再生医学
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药理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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IF 4.2
Yi Chu,Sisi Gui,Yazhen Zheng,Jingwu Zhao,Yaxiang Zhao,Yingying Li,Xiaodong Chen
Non-alcoholic fatty liver disease (NAFLD) is closely associated with the body's energy metabolism. A potential strategy to regulate energy metabolism, combat obesity, and reduce NAFLD is by enhancing adipocyte thermogenesis and increasing energy expenditure. In this study, our objective was to examine the effects of phenolic extracts derived from Magnolia officinalis on the regulation of NAFLD. Specifically, we investigated the impact of Magnolol or Honokiol treatment on high-fat diet (HFD)-induced obese C57BL6/J male mice. Firstly, we monitored energy metabolism, dissected tissues, and analyzed tissue sections. Additionally, we conducted experiments on HepG2 and primary adipocytes to gain insights into the roles of Magnolol or Honokiol. To further understand the effects of these compounds on related signaling pathways and marker genes, we performed molecular docking, dual-luciferase assays, and interfered with target genes. Our findings revealed that Magnolol or Honokiol activate the peroxisome proliferator activated receptor alpha (PPARα) signaling pathway, leading to the alleviation of NAFLD. This activation promotes fatty acid oxidation, reduces lipogenesis, and enhances the expression and secretion of FGF21. Notably, Fibroblast growth factor 21 (FGF21), secreted by the liver, plays a crucial role in improving communication between the liver and adipocytes while also promoting the browning of adipose tissue. Additionally, Magnolol or Honokiol activate the peroxisome proliferator activated receptor gamma (PPARγ) signaling pathway, resulting in increased uncoupling protein 1 (UCP1) expression, heightened heat production in adipose tissue, and anti-obesity. Therefore, Magnolol or Honokiol alleviate NAFLD, promote adipose tissue browning and resist obesity through dual activation of PPARα/γ.
研究领域:
药理学
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代谢
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分子生物学
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营养学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2026
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IF 5.4
Shuai Zhao,Zhenyao Tan,Jiaxin Suo,Yang Bu
Introduction Colorectal cancer liver metastasis (CRLM) is the leading cause of death in colorectal cancer, and nonalcoholic fatty liver disease (NAFLD) promotes CRLM. Lycium barbarum polysaccharides (LBPs), bioactive metabolites of the traditional medicinal plant Lycium barbarum L, inhibit the progression of colorectal cancer and NAFLD by regulating gut microbiota composition. However, their roles in preventing CRLM under NAFLD conditions remain unclear. This study aimed to investigate the preventive effect of LBPs on liver metastasis of colorectal cancer in the context of NAFLD and explore its potential mechanisms. Methods An NAFLD mouse model was established, followed by prophylactic oral administration of LBPs by gavage for 28 days before splenic injection of MC38 colorectal cancer cells to establish liver metastasis. Pseudo-germ-free mice combined with fecal microbiota transplantation were constructed to explore the role of the gut microbiota in the preventive effect of LBPs on CRLM. Gut microbiota and fecal short-chain fatty acids were analyzed by 16S rRNA sequencing and liquid chromatography–mass spectrometry. Spearman’s correlation analysis was used to explore the correlation between bacterial genera and liver lipid metabolism indicators. Serum non-targeted metabolomic profiling and transcriptomic analysis of CRLM cells were performed to elucidate metabolic and molecular mechanisms. Results Under NAFLD conditions, LBPs markedly reduced hepatic metastatic burden, liver weight, and liver-to-body weight ratio. LBPs ameliorated hepatic lipid metabolism and restored colonic barrier integrity in NAFLD mice. The gut microbiota was identified as a critical mediator of LBPs-induced protection against CRLM, and depletion of the microbiota completely abrogated the anti-metastatic effects of LBPs. LBPs enhanced microbial diversity and richness, enriched of short-chain fatty acid-producing bacterial genera, such as Cryptobacteroides, Evtepia, and Bacteroides -H, and elevated colonic butyrate levels. Metabolomic profiling revealed reduced serum acylcarnitines and increased organic acids. Transcriptomic profiling showed upregulation of fibroblast growth factor 21, activation of the PI3K-AKT signaling pathway, and promotion of epithelial–mesenchymal transition in colorectal cancer cells, while LBPs reverse these changes. Discussion LBPs prevent CRLM associated with NAFLD by modulating the gut microbiota, enhancing butyrate production, improving hepatic metabolic homeostasis, and suppressing prometastatic signaling pathways. These findings highlight LBPs as promising preventive agents against CRLM in the setting of metabolic liver disease.
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2025
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IF 2.2
Xiaonan Zhang,Mengxue Xia,Yan Liu,Manwen Yang,Xinzi Zhang,Fenge Chen,Xueqiang Wang,Zhihui Feng,Yingjie Wu,Fang Zhang
Diabetic retinopathy (DR), a leading cause of blindness in the working-age population, is a severe complication of type 2 diabetes mellitus (T2DM). The global increase in T2DM due to high-fat diets necessitates urgent research into the pathogenesis and precision treatments for high-fat-induced DR. Emerging clinical evidence of liver-retina crosstalk offers new mechanistic insights, while the underlying network of metabolites and secreted proteins within the liver-retina axis in high-fat diets induced retinopathy remains unclear. Here, we induced early retinopathy in mice with high-fat diet for 5 weeks, resulting in shortened retinal rods and elevated inflammatory factors, increased activation of microglia and shortened retinal rods. Integrated analysis of RNA-seq data from the retina and liver showed coordinated changes in retinol metabolism pathway and gene networks. Metabolomics and hepatokine analysis suggest that certain liver metabolites (e.g., betaine) and factors (e.g., FGF21) exhibit shared change profiles with the retina under retinal inflammation, uncovering a potential hepatic-ocular network in high-fat-induced DR. This study provides novel insights into distant organ regulation network and identifies potential therapeutic targets for early retinopathy associated with diet-induced metabolic stress, advancing precision treatments strategies.
研究领域:
分子生物学
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基因组学
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代谢组学
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内分泌学
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眼科学
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系统生物学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2026
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IF 2.5
Sijie Li,Haiyu Wang,Pan Zhao,Qitao Zhao
Explored eleven potential ligands in the n-butanol fraction of Gualou-Xiebai-Banxia decoction against FGFR1, βKlotho and FRS2α. • Revealed the interactions between part ligands and three protein targets. • Constructed the first interaction network to unveil the empirical use of the n-butanol fraction of Gualou-Xiebai-Banxia decoction. • Integrating AlphaFold3 predictions with molecular dynamics simulations for the FGFR1, βKlotho, and FRS2α protein complex. • Timosaponin BII exerts effects via the FGF21/FGFR1/βKlotho-FRS2α axis. To systematically deconvolute bioactive components of the n-butanol fraction of Gualou-Xiebai-Banxia decoction (GXB-N) mitigating myocardial ischemia, an integrated drug discovery strategy combining affinity ultrafiltration with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed. This approach was designed to screen specific ligands from the complex matrix that bind to key proteins of the fibroblast growth factor 21 (FGF21) signaling complex, including fibroblast growth factor receptor 1 (FGFR1), βKlotho, and fibroblast growth factor receptor substrate 2α (FRS2α). The thermodynamic stability of identified ligands was evaluated using molecular docking and molecular dynamics simulations, while pharmacological efficacy was validated in an isoproterenol-induced zebrafish model. The screening strategy successfully identified Timosaponin BII as a lead compound with notable binding for the FGFR1/βKlotho-FRS2α complex. In silico simulations demonstrated that Timosaponin BII stably occupies the active pockets of these targets. In vivo assays revealed that Timosaponin BII treatment significantly reversed myocardial ischemia phenotypes, characterized by improved cardiac function and reduced pathological lesions, through the activation of the FGF21 signaling pathway. This study demonstrates the efficacy of the affinity ultrafiltration LC-MS/MS method for clarifying the molecular mechanisms of complex herbal matrices and supports the potential of Timosaponin BII as a therapeutic agent for coronary artery disease. Download: Download high-res image (314KB) Download: Download full-size image
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Zhiwei Huang,Changju Chun,Xinze Li
The management of acute kidney injury (AKI) imposes a significant medical burden. Due to the lack of effective drug transport vehicles, the administration of therapeutic agents for AKI cannot obtain the desired therapeutic effects. Kidney-targeted nanoparticles for renal delivery of drugs have shown promising potential as an emerging strategy for AKI therapy. However, these exogenous nanoparticles are rapidly cleared in the body and fail to achieve the expected renal targeting efficiency. Herein, we prepared the kidney targeting peptide-modified renal tubular epithelial cell membrane to coat zeolite imidazolate framework-8 nanoparticles for FGF21 delivery ( [email protected] ) for AKI treatment. [email protected] could be efficiently internalized by renal cells and exhibited antioxidative, antiapoptotic and anti-inflammatory effects. A septic AKI murine model was established to assess the in vivo performance of [email protected] The results showed that injected [email protected] specifically accumulated in the injured kidney and exerted good renoprotective effects. This study provides an innovative thread for precise drug delivery in the treatment of various renal diseases.
研究领域:
纳米技术
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药学
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生物医学工程
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肾脏生理学
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药物递送系统
✓ 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）