JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2026
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IF 4.1
Jingchun Wang,Mingzheng Han,Jingling Yu,Bohao Chen,Shuaihao Guo,Ziqi Wu,Hai Huang,Zhaoxin Tang,Jianzhao Liao,Jianying Guo
Copper (Cu) exposure poses significant threats to renal health yet effective mitigation strategies remain scarce. Kaempferol (Kae) is a naturally occurring flavonoid with well-documented antioxidant and anti-apoptosis activities. Nevertheless, its protective effects in renal copper poisoning and the underlying molecular mechanisms have not been fully elucidated. This study integrated network toxicology, pharmacology, molecular docking, molecular dynamics simulation and a broiler model preliminarily revealed the mechanism of Kae alleviates Cu-induced nephrotoxicity (CuN). The potential targets of CuN scanned from Comparative Toxicogenomics Database (CTD), GeneCards database (GC) and the targets of Kae scanned from SwissTargetPrediction, PharmMapper database were used to perform GO and KEGG enrichment analysis. STRING and Cytoscape were employed to constructed PPI networks and locked on core targets. Molecular docking and dynamics simulations were used to investigate the binding affinity and stability of Kae with the core targets. A broiler model to further validate the impact of Kae on key signaling pathways. Notably, Kae effectively ameliorated histopathological damage caused by excess Cu and restored renal function ( P < 0.05). Network results revealed the involvement of apoptosis and MAPK signaling pathway, with Caspase-3 (CASP3) and Mitogen-activated protein kinase 8 (MAPK8) identified as core targets. In vivo experiments demonstrated that Cu significantly up-regulated the levels of Cleaved-CASP3 and phosphorylated MAPK8 and the expression of genes and proteins involved in promoting endogenous apoptosis ( P < 0.05), while Kae markedly reversed these effects and reduced TUNEL staining positive rate from 43.83% to approximately 12.84% ( P < 0.05). In summary, our findings demonstrate that Kae alleviates CuN by targeting the apoptotic process and the MAPK/JNK signaling axis, highlighting its potential as a natural therapeutic agent against heavy metal-induced nephrotoxicity in agricultural settings.
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高影响因子
Journal of Macromolecular Science Part A-Pure and Applied Chemistry
·
2023
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IF 2.5
Yunxin Zhang,Jiange Liu
Current clinical therapies for invasive breast cancer have low therapeutic effectiveness and substantial systemic adverse effects, leading to poor patient compliance. In this investigation, we developed dual anticancer drugs (sorafenib (SFB) and kaempferol (KMF)) encapsulated in PEGylated gold nanomaterial (PEG-AuNPs@SFB/KMF) for a drug delivery system targeting breast cancer to circumvent this problem. Subsequent research examined whether pH affects drug release. The current study results show that sorafenib and kaempferol work better together than each treatment individually in eliciting cytotoxic effects. In vitro cytotoxicity studies confirmed that PEG-AuNPs@SFB/KMF were more effective than sorafenib alone in MCF-7 and MDA-MB-231 cells, with less toxicity in NIH3T3 cells. The cancer cell proliferation was measured by Click-iT EdU assay, which indicates that the NPs effectively induce apoptosis in cancer cells. The different biochemical staining (acridine orange and ethidium bromide (AO-EB and nuclear staining (DAPI)) methods confirmed the morphological investigation of the cells. PEG-AuNPs@SFB/KMF increased apoptosis ratio, confirmed by flow cytometric analysis via Annexin V-FITC/PI staining methods. Therefore, we believe that the built multifunctional nanocarrier based on developed nanoparticle delivery could be an alternative therapeutic strategy for breast cancer therapy.
研究领域:
纳米医学
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药学
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肿瘤学
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药物递送系统
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生物化学
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Life-Basel
·
2021
·Vol. 11
·期 5
·445
·
IF 3.817
Yang Deng,Ji Ma,Xin Weng,Yuqin Wang,Maoru Li,Tingting Yang,Zhiyang Dou,Zhiqi Yin,Jing Shang
NAFLD (non-alcoholic fatty liver disease) is one of the most prominent liver diseases in the world. As a metabolic-related disease, the development of NAFLD is closely associated with various degrees of lipid accumulation, oxidation, inflammation, and fibrosis. Ilex chinensis Sims is a form of traditional Chinese medicine which is used to treat bronchitis, burns, pneumonia, ulceration, and chilblains. Kaempferol-3-O-glucuronide (K3O) is a natural chemical present in Ilex chinensis Sims. This study was designed to investigate the antioxidative, fat metabolism-regulating, and anti-inflammatory potential of K3O. A high-cholesterol diet (HCD) was used to establish steatosis in larval zebrafish, whereby 1mM free fatty acid (FFA) was used to induce lipid accumulation in HepG2 cells, while H2O2was used to induce oxidative stress in HepG2. The results of this experiment showed that K3O reduced lipid accumulation and the level of reactive oxygen species (ROS) both in vivo (K3O, 40 μM) and in vitro (K3O, 20 μM). Additionally, K3O (40 μM) reduced neutrophil aggregation in vivo. K3O (20 μM) also decreased the level of malondialdehyde (MDA) and significantly increased the level of glutathione peroxidase (GSH-px) in both the HCD-induced larval zebrafish model and H2O2-exposed HepG2 cells. In the mechanism study,keap1,nrf2,tnf-α, andil-6mRNA were all significantly reversed by K3O (20 μM) in zebrafish. Changes in Keap1 and Nrf2 mRNA expression were also detected in H2O2-exposed HepG2 cells after they were treated with K3O (20 μM). In conclusion, K3O exhibited a reduction in oxidative stress and lipid peroxidation, and this may be related to the Nrf2/Keap1 pathway in the NAFLD larval zebrafish model.Keywords:non-alcoholic fatty liver disease;kaempferol-3-O-glucuronide;oxidative stress;inflammation;high-cholesterol diet.
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高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Xiaotian Xu,Xinhui Li,Xingshu Wei,Xiaoqun Duan,Yuhui Wang
Passion fruit peel fermentation extract (PFPFE) increased gastrointestinal transport power and fecal moisture content, protected the structural integrity of colon tissue, and reduced inflammatory infiltration. PFPFE also increased secretion of the ET-1, GAS, MTL, and SP, and decreased secretion of the inhibitory SS and VIP. In addition, PFPFE alleviated perirectal redness and hemorrhage in hemorrhoid mice, and downregulated levels of the serum inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). In this study, we also analyzed the main active components and core targets of PFPFE for alleviating constipation and hemorrhoids through network pharmacology, and predicted its mechanism of action. Finally, we carried out Western blot experiments to verify that PFPFE and its active component kae alleviates constipation and hemorrhoids in mice by downregulating ESR1 and PI3K/Akt pathways. These results provide a scientific basis for the development of PFPFE as a functional food for alleviating constipation and hemorrhoids.
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Journal of Applied Spectroscopy
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2023
·Vol. 90
·期 4
·883-892
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IF 0.7
Shi Ying,Guo Ya-Dan,Mi Yi-Duo,Cheng Jia,Dong Wen,Zhang Gao-Feng,Zeng Yi
The antioxidant activities of flavonoid mixtures can be used to investigate the synergistic antioxidant mechanism of flavonoids. The antioxidant capacities of three flavonoids (quercetin, baicalein, and daidzein) and β-carotene in binary and ternary mixtures with kaempferol were analyzed using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition assay by means of absorption spectroscopy. The results showed that the number of hydroxyl groups and o-hydroxyl groups had a significant effect on the antioxidant activity of the flavonoids, and the mixture of kaempferol, quercetin, and baicalein showed optimal synergistic antioxidant activity. Compared with quercetin and baicalein, kaempferol had the fastest inhibition rate, and multiple prolonged kinetic processes associated with the scavenging of DPPH radicals occurred in mixtures of kaempferol with the other flavonoids and β-carotene. Kaempferol has a potential synergistic antioxidant effect when mixed with daidzein and β-carotene, and the results suggested that this may be due to the regeneration of kaempferol after antioxidation. By means of classic UV-Vis spectroscopy, reaction details of the synergistic antioxidant process of DPPH radical scavenging by flavonoids can be obtained.
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ACS Applied Materials & Interfaces
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2026
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IF 7.8
Yuhui Liu,Ning Zhou,Yumeng Luo,Xinyue Guan,Wenxin Meng,Xing Yu,Quanli Li,Qunlin Zhang,Xianwen Wang,Guomin Wu
This study aims to fabricate a scaffold based on natural herbal active substances, achieving antibacterial, anti-inflammatory, and osteogenic activities by graded and sustained drug release, overcoming the high cost and instability of growth factors in conventional bone defect scaffolds. Coaxial electrospinning was employed to construct a scaffold with silk fibroin (SF)/polycaprolactone (PCL)/kaempferol (KAE) as the shell and icariin (ICA) as the core, preparing nanofibrous scaffolds (ICA@SF/PCL/KAE). Comprehensive characterizations confirmed the co-axial structure of the nanofibers and successful drug loading and favorable release profiles of KAE and ICA, as well as the significantly enhanced mechanical performance. The KAE-loaded scaffold exerted outstanding antibacterial activity, while all of the drug-containing scaffolds maintained excellent cytocompatibility. In LPS-induced inflammatory environments, macrophages co-cultured on KAE-containing scaffolds exhibited markedly reduced reactive oxygen species and nitric oxide production, along with a decreased M1 macrophage ratio and an increased M2 macrophage ratio. RT-PCR results demonstrated that KAE-loaded scaffolds downregulated pro-inflammatory gene expression and upregulated anti-inflammatory gene expression. In vitro osteogenic induction revealed that the incorporation of KAE and ICA, especially ICA, remarkably enhanced osteogenic activity of the nanofibrous scaffolds. Under inflammatory conditions, KAE-containing scaffolds exhibited superior regulation of the osteogenic immune microenvironment compared with ICA-containing scaffolds. Notably, the ICA@SF/PCL/KAE scaffold containing both components achieved the optimal performance in all of the above in vitro experiments. Finally, rat cranial defect experiments further verified the excellent osteogenic efficacy of ICA@SF/PCL/KAE in vivo. Collectively, the ICA@SF/PCL/KAE core-shell nanofibrous scaffold offers an innovative approach for clinical bone defect treatment and expands the application potential of natural herbal active substances.
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Evidence-based Complementary and Alternative Medicine
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2022
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IF 2.65
Ziqian Xu,Yihui Xie,Jun Song,Juntao Huang,Weimin Shi
Objective. This study aimed to explore the mechanisms of Baishi tablets (BSTs) in the treatment of vitiligo through network pharmacology-based identification and experimental validation. Methods. In brief, the compounds and related targets of BST were extracted from the TCMSP database, and disease information was obtained from the OMIM, GeneCards, PharmGkb, TTD, and DrugBank databases. A Venn diagram was generated to visualize the common targets of BST and vitiligo. GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways. The PPI network and core gene subnetwork were constructed using STRING and Cytoscape software. In addition, the measurement of apoptosis in PIG1 cells and intracellular reactive oxygen species were measured using quercetin (QU), luteolin (LU), and kaempferol (KA) to protect melanocytes from oxidative stress. Results. A total of 55 compounds with 236 targets and 1205 vitiligo-related genes were obtained from the TCMSP database. GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways, revealing that BST may cure vitiligo by influencing the biological processes of cellular oxidative stress and related signaling pathways. A critical subnetwork was obtained with 13 core genes by analyzing the PPI network, which includes HMOX1, CXCL8, CCL2, IL6, MAPK8, CASP3, PTGS2, AKT1, IL1B, MYC, TP53, IFNG, and IL2. Furthermore, a molecular docking analysis was conducted to simulate the combination of compounds and gene proteins, reflecting that QU, LU, and KA can strongly bind the core genes. Through a series of experimental validations, we found that QU, LU, and KA could attenuate H2O2-induced apoptosis in melanocytes. Further evidence revealed that QU, LU, and KA could enhance the scavenging of intracellular reactive oxygen species (ROS). Conclusion. Based on the results of network pharmacology analysis and experimental verification, QA, LU, and KA can be utilized to protect PIG1 cells by inhibiting oxidative stress and reducing the intracellular level of ROS. This may explain the underlying mechanism of BST therapy and provide a novel strategy for the treatment of vitiligo.
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JOURNAL OF SEPARATION SCIENCE
·
2025
·Vol. 48
·期 4
·e70126
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IF 2.8
Wenlin Zhong,Fangping Liang,Lingling Zhong,Jiming Ou,Jianfeng He,Quanzhou Wu
In this study, kaempferol molecularly imprinted monolithic columns (MIMCs) featuring a homogeneous pore structure and high separation ability were successfully prepared by surface imprinting on silica monoliths. These columns were then used to separate flavonoids from the hydrolysate of Ginkgo leaves. The preparation process involved three simple steps: preparation of silica monoliths, functionalization of the silica surface, and polymerization of the imprinting system onto the silica surface. The resulting MIMCs exhibited a homogeneous pore structure, high surface area (>100 m 2 /g), high porosity (ca. 74%), and good permeability (3.0 − 3.9 × 10 −15 m 2 ). The chromatographic separation performance of the MIMCs prepared on amino-functionalized silica monoliths was significantly superior to those prepared on thiol and vinyl-functionalized silica monoliths. The MIMCs prepared on amino-functionalized silica monoliths (I.D. 4.6 × 20 mm) could nearly achieve baseline separation of four structurally similar flavonoids: genistein, kaempferol, isorhamnetin, and quercetin. In addition, these MIMCs exhibited excellent selectivity in the chromatographic separation of flavonoids from the hydrolysate of Ginkgo leaves. However, when used as SPE adsorbents, the MIMCs prepared on thiol and vinyl-functionalized silica monoliths were superior to those on amino-functionalized silica monoliths in terms of purification of flavonoids from the Ginkgo hydrolysate. This study may be of instructive significance to the facile preparation of MIMCs for the high-selectivity separation and analysis of target components in complex natural systems.
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