ARCHIVES OF MEDICAL RESEARCH
·
2020
·
IF 2.093
Zexin Li,Ying Wang,Yu Zhang,Xiao Wang,Baoqin Gao,Yan Li,Rong Li,Jianguo Wang
Background and Aims Hepatic ischemia-reperfusion injury (IRI) is the main leading cause of morbidity and mortality of patients after liver surgery and transplantation. Fisetin, a kind of flavonoid, has been reported to protect against myocardial and cerebral IRI. However, the effects of fisetin on liver IRI were poorly investigated. Methods C57BL/6 mice were used to establish the liver IRI model in vivo . Intraperitoneal injection of fisetin was performed one hour before IR treatment (1 h ischemia and 6h reperfusion). In vitro experimental study was conducted using AML-12 hepatocytes with 1 h hypoxia and 12 h reoxygenation (HR) treatment. Tissue damage was evaluated through serum AST and ALT levels and hematoxylin-eosin (HE) staining. Cell apoptosis was assessed by TUNEL staining and protein levels of Bax, Bcl-2, cleaved-caspase-3, and cleaved-PARP. Oxidative stress was evaluated by ROS and MDA levels and the activity of SOD and GSH-Px. Immunohistochemistry and immunofluorescence assay were performed to observe the translocation of Nrf2 from the cytoplasm into the nucleus. Results The histopathological assessment showed that fisetin attenuated IR-induced liver damage obviously. Besides, fisetin served a protective role in IR liver to alleviate cell apoptosis and oxidative stress in vivo and in vitro . Introduction of high concentration of fisetin promoted the translocation of Nrf2 from the cytoplasm into the nucleus, increasing protein expression of its downstream elements, at least HO-1 in IR liver tissues and hepatocytes after HR. Inhibition of Nrf2 could reverse the effects of fisetin on cell viability, cell apoptosis, and also oxidative stress of HR hepatocytes, suggesting that Nrf2 signaling was necessary in fisetin-mediated regulations of liver IRI. Conclusion Fisetin alleviates liver damage, cell apoptosis, and oxidative stress induced by liver IRI, at least through Nrf2/HO-1 signaling pathway, suggesting that fisetin could be considered as a targeted drug for liver IRI treatment.
研究领域:
药理学
·
肝病学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Shifeng Xiao,Yafei Lu,Qiuping Wu,Jiaying Yang,Jierui Chen,Suyue Zhong,David Eliezer,Qiulong Tan,Chengchen Wu
Alzheimer's disease is a neurodegenerative disease which severely impacts the health of the elderly. Current treatments are only able to alleviate symptoms, but not prevent or cure the disease. The neurofibrillary tangles formed by tau protein aggregation are one of the defining characteristics of Alzheimer's disease, so tau protein has become a key target for the drug design. In this study, we show that fisetin, a plant-derived polyphenol compound, can inhibit aggregation of the tau fragment, K18, and can disaggregate tau K18 filaments in vitro . Meanwhile it is able to prevent the formation of tau aggregates in cells. Both experimental and computational studies indicate that fisetin could directly interact with tau K18 protein. The binding is mainly created by hydrogen bond and van der Waal force, prevents the formation of β-strands at the two hexapeptide motifs, and does not perturb the secondary structure or the tubulin binding ability of tau protein. In summary, fisetin might be a candidate for further development as a potential preventive or therapeutic drug for Alzheimer's disease.
研究领域:
神经科学
·
药理学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS LETTERS
·
2023
·
IF 3
Sichao Gu,Xuefeng Zhou,Xingshi Yuan,Yunliang Zhu,Hui Zhang,Lei Xu,Li Li
Infected diabetic wounds (IDW) are difficult to heal and lead to serious complications such as amputation. Inspired by natural elements, we developed an injectable photocurable hydrogel platform based on methacrylamide silk fibroin, encapsulated with ZnO NPs and plants derived fisetin, for accelerating IDW healing. The combined release of ZnO NPs and fisetin inhibited the biofilm formation of Staphylococcus aureus on the wound surface, while fisetin possessed the immunomodulatory function of promoting macrophage M2 polarization and the release of anti-inflammatory cytokines to promote tissue healing. Therefore, this natural hydrogel composite platform can be applied as a potential wound dressing with good biocompatibility.
研究领域:
生物材料学
·
免疫学
·
医学
✓ 已验证
产品关联
DOI
高影响因子
iScience
·
2026
·
IF 4.5
Hanlin Yang,Weiwei Li,Hailong Zhang,Yameng Liu,Miaomiao Cui,Yurong Zhu,Li Hou,Shaoju Min,Jie Ren,Yujie Tan
Conventional cervical cancer therapies often cause severe side effects and face recurrence challenges. Although the natural flavonoid fisetin (FIS) exhibits strong anticancer properties, its clinical utility is restricted by poor aqueous solubility. To overcome this, we engineered a tumor-targeting nanotherapeutic, PEG-FA@ZIF-8@FIS, by encapsulating FIS within a zeolitic imidazolate framework-8 (ZIF-8) core surface-functionalized with polyethylene glycol-folic acid(PEG-FA). Both in vitro and in vivo models demonstrate that this system effectively suppresses cancer cell proliferation, migration, and tumor growth with excellent biocompatibility. Mechanistically, transcriptomic and lipidomic analyses reveal that PEG-FA@ZIF-8@FIS exerts its anticancer effects by downregulating aquaporin-3 (AQP3) expression, which subsequently disrupts tumor lipid metabolism. By linking AQP3 inhibition to metabolic impairment via a targeted delivery platform, this work establishes a highly biocompatible and effective translational strategy for cervical cancer intervention.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL PHYSICS LETTERS
·
2024
·
IF 2.8
Yan Liu,Yan Ding,Yongchun Tan,Jian Luo
Slow solvation dynamics and abundant non-bonding interactions in polymer matrix can modulate photophysical properties of guest chromophores. In this work, we used fisetin as a fluorescent probe to explore the microenvironment in poly vinyl alcohol (PVA) matrix and its effect on excited-state proton transfer (ESPT). Compared to in PVA solution, fluorescence of fisetin in PVA film is largely enhanced and ESPT barrier is increased. Both bulk polarity of PVA film and site-specific intermolecular hydrogen bonding between water and fisetin were determined to contribute to anomalous absorption and emission properties absent in solutions.
研究领域:
化学
·
材料科学
·
光学
✓ 已验证
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2024
·
IF 4.4
Jiaqi Fang,Bo Xu,Xuehan Jin,Feng Chen,Shuhao Liu,Shengfu Liu,Sen Wang,Fan Zhang,Kaihang Song,Jianguang Wang,Liping Nan,Junjian Liu
Peripheral nerve injuries represent a prevalent and severe category of damage resulting from traumatic incidents. Predominantly, the deficiency in nerve regeneration can be ascribed to enduring inflammatory reactions, hence imposing substantial clinical implications for patients. Fisetin, a flavonoid derived from plants, is naturally present in an array of vegetables and fruits, including strawberries, apples, onions, and cucumbers. It exhibits immunomodulatory properties through the reduction of inflammation and oxidative stress. In the present research, a nerve defect was addressed for the first time utilizing a scaffold primed for controlled fisetin release. In this regard, fisetin-loaded chitosan hydrogels were incorporated into the lumen of polycaprolactone (PCL) nerve guide conduits (NGCs). The hydrogel maintained a steady release of an appropriate fisetin dosage. The study outcomes indicated that the fisetin/chitosan/polycaprolactone (FIS/CS/PCL) NGCs amplified Schwann cell proliferation and neural expression, curtailed oxidative stress, alleviated inflammation, and improved functions, electrophysiological properties, and morphology. This pioneering scaffold has potential to contribute significantly to the field of neuroengineering. This article is protected by copyright. All rights reserved
研究领域:
生物医学工程
·
神经科学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Nayun Kim,Junhye Kwon,Ui Sup Shin,Joohee Jung
Colorectal cancer (CRC) is associated with high incidence and mortality rates. Targeted therapies for CRC cause various adverse effects, necessitating the development of novel approaches to control CRC progression. In this milieu, we investigated the anti-CRC effects of fisetin, a natural plant flavonoid. Cytotoxicity was performed in CRC patient-derived organoids (30 T and 33 T). Fisetin-induced tumor growth was evaluated in a CRC patient-derived organoid xenograft (PDOX) model. RNA sequencing, immunohistochemistry, and western blotting were performed subsequently. Fisetin significantly decreased organoid viability in a dose-dependent manner. In the PDOX model, fisetin significantly delayed tumor growth, showing a decrease in Ki-67 expression and the induction of apoptosis. In tumor tissues, four genes were identified as differentially expressed between the control and fisetin-treated groups. Among these, A-kinase anchoring protein 12 ( AKAP12 ) level was significantly increased by fisetin treatment (fold change > 2, p < 0.05). Notably, fisetin significantly inhibited vascular endothelial growth factor (VEGF) and epithelial cell adhesion molecule (EpCAM) via upregulation of AKAP12. Our results demonstrate the upregulation of AKAP12 mRNA and inhibition of angiogenesis by fisetin as a therapeutic strategy against CRC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2019
·
IF 4.18
Licong Zhao,Jiaqi Zhang,Lingyun Pan,Long Chen,Yu Wang,Xinhua Liu,Lisha You,Yiqun Jia,Cheng Hu
Background Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Fisetin (FST) is a phenolic compound that has been isolated from many natural products. Purpose Our aim is to study the protection effect and mechanisms of FST on APAP-induced hepatotoxicity in endogenous metabolism and metabolomics in vitro and in vivo . Methods FST was i.g. administered to mice at 10 , 20 and 40 mg/kg for 7 days and a single dose of APAP (400 mg/kg) was given on the last day. Serum and tissue were collected for biochemical analysis . L-02 cells were used to assess cell viability . LC–MS was used to study the metabolic fingerprinting in vivo and vitro . PCA and OPLS-DA were used to search the potential biomarkers (VIP > 1, p < 0.05). The pathway analysis was conducted on Metaboanalyst 4.0. Then liver oxidative stress indices and glutathione markers were examined using PCR and kits. Results ALT , AST, liver histological observation and cell viability results showed that FST could reverse APAP induced toxicology in mice and L-02 cells. In metabolomics study, 26 metabolites in vitro and 60 metabolites in vivo were identified by searching in the library and most of them decreased to normal level in FST treatment . It is observed in pathway analysis that the most significant pathway was glutathione metabolism. Furthermore, the results of mRNA and immunofluorescence showed that FST suppressed ROS formation in liver tissue and L-02 cells, as well as restored the expression of GPX1 , GST and other antioxidative enzymes genes. Conclusion Our results indicate that FST prevented APAP-induced hepatotoxicity by regulating glutathione metabolism and the expression of related antioxidative signals.
研究领域:
药理学
·
毒理学
·
代谢组学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomaterials
·
2020
·Vol. 10
·期 2
·322
·
IF 4.324
Lin-Fei Chen,Pei-Yao Xu,Chao-Ping Fu,Ranjith Kumar Kankala,Ai-Zheng Chen,Shi-Bin Wang
Due to its hydrophobicity, fisetin (FIS) often suffers from several limitations in terms of its applicability during the fabrication of pharmaceutical formulations. To overcome this intrinsic limitation of hydrophobicity, we demonstrate here the generation of poly (vinyl pyrrolidone) (PVP)-encapsulated FIS nanoparticles (FIS-PVP NPs) utilizing a supercritical antisolvent (SAS) method to enhance its aqueous solubility and substantial therapeutic effects. In this context, the effects of various processing and formulation parameters, including the solvent/antisolvent ratio, drug/polymer (FIS/PVP) mass ratio, and solution flow rate, on the eventual particle size as well as on distribution were investigated using a 23factorial experimental design. Notably, the FIS/PVP mass ratio significantly affected the morphological attributes of the resultant particles. Initially, the designed constructs were characterized systematically using various techniques (e.g., chemical functionalities were examined with Fourier-transform infrared (FTIR) spectroscopy, and physical states were examined with X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) techniques). In addition, drug release as well as cytotoxicity evaluations in vitro indicated that the nanosized polymer-coated particles showed augmented performance efficiency compared to the free drug, which was attributable to the improvement in the dissolution rate of the FIS-PVP NPs due to their small size, facilitating a higher surface area over the raw form of FIS. Our findings show that the designed SAS process-assisted nanoconstructs with augmented bioavailability, have great potential for applications in pharmaceutics.Keywords:supercritical fluid technology;fisetin;nanofabrication;antitumor
研究领域:
药学
·
纳米技术
·
药物递送系统
·
癌症研究
·
超临界流体技术
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2018
·
IF 3.382
T.H. Wang,S.Y. Wang,X.D. Wang,H.Q. Jiang,Y.Q. Yang,Y. Wang,J.L. Cheng,C.T. Zhang,W.W. Liang,H.L. Feng
Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease commonly found to include a copper/zinc superoxide dismutase (SOD1) gene mutation. Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. The possible effect of fisetin in ALS has not been clarified as of yet. We investigated whether fisetin affected mutant hSOD1 ALS models. Three different hSOD1-related mutant models were used: Drosophila expressing mutant hSOD1 G85R , hSOD1 G93A NSC34 cells, and transgenic mice. Fisetin treatment provided neuroprotection as demonstrated by an improved survival rate, attenuated motor impairment, reduced ROS damage and regulated redox homeostasis compared with those in controls. Furthermore, fisetin increased the expression of phosphorylated ERK and upregulated antioxidant factors, which were reversed by MEK/ERK inhibition. Finally, fisetin reduced the levels of both mutant and wild-type hSOD1 in vivo and in vitro , as well as the levels of detergent-insoluble hSOD1 proteins. The results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations probably by activating ERK, thereby providing a potential treatment for ALS.
研究领域:
神经科学
·
药理学
·
分子生物学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2012
·
IF 3.898
Shujuan Xu,Yong Shao,Kun Ma,Qinghua Cui,Guiying Liu,Fei Wu
Many efforts have been made for the developments of aptamers due to their wide applications for various targets. In this work, we tried to use an abasic site (AP site) that was embeded in a double-stranded DNA as a binding pocket for fisetin . With the AP site being wholly opposed and flanked by thymines (named T-T aptamer), the aptamer exhibits high binding selectivity and sensitivity for fisetin over the other flavonoids such as morin, rutin , apigenin , kaempferol , myricetin , quercetin , luteolin , baicalin , naringenin , genistein , chrysin , and galangin . Upon binding to the AP site, fisetin experiences a significant enhancement in fluorescence emisson by favoring the occurrence of its excited-state intramolecular proton transfer (ESIPT) reaction. The detection limit is about 50 nM at a signal-to-noise ratio of 3. Therefore, the realization for fisetin's selective analysis is beneficial from the novel aptamer design without any fluorophore modification. Thus, the almost negligible fluorescence background from the aptamer is achieved in our method.
研究领域:
生物化学
·
分析化学
·
药物化学
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Huanchen Yao,Dayang Wang,Jiashuo Ye,Hailin Cong,Bing Yu
Ethnopharmacological relevance Lung cancer is a common respiratory cancer worldwide, which seriously threatens people's lives. The current treatment of lung cancer is not satisfactory. Traditional Chinese medicine records that Hedyotis diffusa Willd (HDW) has effects that include clearing heat and detoxifying, promoting diuresis and dehumidification, relieving pain and resolving masses, and exhibiting anti-cancer properties. It has shown extraordinary therapeutic value in the clinical practice of traditional Chinese medicine. It is commonly used to treat various tumors, inflammation, and other diseases. Aim of the study The purpose of this experiment is to isolate the components with anti-lung cancer effects from HDW and to explore its anti-lung cancer effect and mechanism through network pharmacology and in vitro cell experiments in order to find more effective and less side effects—anticancer drugs. Materials and methods We used ethanol to extract HDW preliminarily and then used ethyl acetate, n-butanol, petroleum ether, and water to extract it, obtaining the ethyl acetate fraction with the highest inhibition rate on lung cancer H1299 cells. The silica gel column purification, TOF, and nuclear magnetic resonance analysis yielded the Fisetin, which has an inhibitory effect on H1299 cells. The mechanism and application of Fisetin in inhibiting lung cancer were explored by network pharmacology and in vitro cell experiments. Results Using network pharmacology to explore the mechanism of Fisetin inhibiting lung cancer, 115 Fisetin targets, and 26,857 lung cancer targets were obtained, and 90 GO functions and 19 KEGG pathways were obtained (P < 0.01). Molecular docking results demonstrated that target protein-drug binding was stable. Afterward, the toxicity of Fisetin to H1299 cells was verified by in vitro cell experiments. MTT, live-dead staining, and confocal microscopy all showed that Fisetin had a good inhibitory effect on H1299 cells and had good cell compatibility. Through Western blot analysis, Fisetin can reduce the protein content of PI3K, MTOR, HIF1A and VEGFA. And it can reduce the mRNA expression levels of HIF1A and VEGFA. Moreover, Fisetin can also increase the expression of tumor suppressor molecule PTEN protein and mRNA in H1299 cells. Conclusions Fisetin and HDW can successfully stop lung cancer H1299 cells from growing. The mechanism of Fisetin may be related to the inhibition of PI3K/MTOR/HIF1A/VEGFA signaling pathway.
研究领域:
药理学
·
肿瘤学
·
生物信息学
·
细胞生物学
·
药物化学
✓ 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）