Plants-Basel
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2025
·Vol. 14
·期 1
·120
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IF 4.1
Fangjie Li,Chen Yang,Maoye Li,Su Liu,Kuo Xu,Xianjun Fu
Valsa mali(V. mali) is a necrotrophic fungus responsible for apple Valsa canker, which significantly diminishes apple production yields and quality in China. Our serendipitous findings revealed that genistein significantly inhibits the mycelial growth ofV. mali, with an inhibition rate reaching 42.36 ± 3.22% at a concentration of 10 µg/mL. Scanning electron microscopy analysis revealed that genistein caused significant changes in the structure ofV. mali, including mycelial contraction, distortion, deformity, collapse, and irregular protrusions. Transmission electron microscopy analysis revealed leakage of cellular contents, blurred cell walls, ruptured membranes, and organelle abnormalities. Genistein has been shown to increase reactive oxygen species levels inV. malimycelia, as demonstrated by 2′,7′-dichlorofluorescin diacetate staining. This increase was associated with a decrease in superoxide dismutase activity alongside increases in catalase and peroxidase activities. These changes collectively disrupted the oxidative equilibrium, leading to the induction of oxidative stress. The transcriptomic analysis revealed 13 genes enriched in this process, linked to unsaturated fatty acid biosynthesis (three downregulated DEGs), saturated fatty acid biosynthesis (three upregulated and six downregulated DEGs), and fatty acid metabolism (four upregulated and nine downregulated DEGs). Additionally, the downregulated DEGs VMIG_07417 and VMIG_08675, which are linked to ergosterol biosynthesis, indicate possible changes in membrane composition. In conjunction with the qRT-PCR results, it is hypothesized that genistein exerts an antifungal effect onV. malithrough ROS-mediated lipid peroxidation. This finding has the potential to contribute to the development of novel biological control agents for industrial crops.
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Materials Today Bio
·
2025
·
IF 10.2
Qingyu Zhao,Yong Li,Qian Sun,Ronggui Wang,Haoran Lu,Xinyi Zhang,Lun Gao,Qiang Cai,Baohui Liu,Gang Deng
Glioblastoma (GBM) is the most prevalent and aggressive primary malignant brain tumor in adults, known for its poor prognosis and resistance to conventional treatments. The blood-brain barrier (BBB) presents a significant challenge in delivering effective treatments. In this study, we developed a carrier-free, self-assembled nanosystem using genistein (GE), a naturally occurring isoflavone, to enhance therapeutic delivery across the BBB. GE nanoparticles (GE NPs) were synthesized via solvent emulsification evaporation, in uniform spherical particles (∼180 nm), stabilized by hydrogen bonding and π-π interactions. The GE NPs demonstrated optimal physicochemical properties, including stability, high BBB permeability, prolonged circulation time. In vitro studies revealed that GE NPs inhibited GBM cell proliferation, induced apoptosis and suppressed epithelial-mesenchymal transition (EMT) by promoting the degradation of MMP9. In vivo, GE NPs significantly reduced tumor growth and extended survival in an orthotopic GBM mouse model, outperforming temozolomide treatment. Mechanistic analysis indicated that GE NPs inhibited the degradation of the extracellular matrix by targeting the catalytic domain of MMP9, thereby effectively suppressing the EMT of GBM. This research highlights the potential of GE NPs as a novel therapeutic approach for GBM, addressing drug delivery challenges while improving anti-tumor efficacy. Further optimization for enhanced tumor retention and exploration of combination therapies may improve clinical outcomes (Graphical ).
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GREEN CHEMISTRY
·
2025
·
IF 9.2
Jia Bao Zhang,Wei Chen,Yong Jun Yang,Zhen Zhen Liu
Genistein, a plant-derived isoflavone with pharmaceutical value, is conventionally obtained through ecologically detrimental extraction processes that rely on large-scale plant harvesting and hazardous solvents. Here, we report the discovery of native genistein biosynthesis in the Paenibacillus jilinensis, which inherently produces 5.7 mg L−1 genistein via the phenylalanine branch of the phenylpropanoid pathway. This pathway mirrors plant flavonoid synthesis but operates through seven bacterial enzymes (PjPAL, PjC4H, Pj4CL, PjCHS, PjCHI, PjIFS, and PjHID) with about 30% sequence homology to the corresponding protein sequences in plants, suggesting evolutionary convergence. To leverage this native capability for sustainable production, we constructed a genome-scale metabolic model (GSMM YPG26) with 1636 reactions and 717 genes to rationally optimize carbon flux. Metabolic engineering elevated genistein titers by 9.3-fold to 52.8 mg L−1 without introducing heterologous plant genes. Green-chemistry analysis further showed that P. jilinensis-ΔGLN achieves 92% less waste than soybean extraction and up to one order of magnitude better than state-of-the-art E. coli and yeast systems. It is crucial that this bacterial platform requires only a basic culture medium for sustained production, and eliminates dependence on medicinal plants. Our findings reveal P. jilinensis as a naturally gifted genistein producer and a green chassis for industrial isoflavone synthesis, aligning with green chemistry goals of waste prevention and bio-based process innovation.
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Preventive Nutrition and Food Science
·
2026
·Vol. 31
·期 3
·pnf
·
IF 2.8
Cun Ku,Hanxiao Feng,Manni Wu,Jiyu Xie,Kuan Jiang,Chenhang Li,Zichun Qin,Abdrakhmanov Ayan,Yang Zhang
Genistein is a dietary isoflavone that is abundant in soy products and has been suggested to exert cardiovascular protective effects; however, its role in hypertension remains incompletely defined. Here, we investigated whether genistein ameliorates angiotensin II (Ang II)-induced hypertension and endothelial dysfunction using complementary in vivo , ex vivo , and in vitro models. The oral administration of genistein substantially attenuated Ang II-induced elevations in systolic and diastolic blood pressure in mice without affecting body weight. Histological analyses revealed that genistein alleviated aortic wall thickening and smooth muscle hypertrophy, whereas vascular reactivity assays demonstrated improved endothelium-dependent relaxation while preserving the endothelium-independent responses. In isolated murine aortic rings, genistein reversed Ang II-induced hypercontractility and restored acetylcholine-mediated vasodilation. Furthermore, in human umbilical vein endothelial cells, genistein suppressed the Ang II-induced overproduction of reactive oxygen species (ROS) and restored nitric oxide (NO) bioavailability. Mechanistically, genistein improved endothelial redox-NO coupling, accompanied by transcriptional remodeling of the redox/NO axis [e.g., suppression of nicotinamide adenine dinucleotide phosphate oxidase 4 ( NOX4 ) and nitric oxide synthase 2 ( NOS2 ) and restoration of nitric oxide synthase 3 ( NOS3 )], which is consistent with reduced ROS and enhanced NO bioavailability. Collectively, our findings identify genistein as a potent endothelial-protective agent that ameliorates Ang II-induced hypertension, highlighting its therapeutic potential in cardiovascular disease driven by vascular dysfunction.
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ACS Sustainable Chemistry & Engineering
·
2023
·
IF 8.4
Junhua Ding,Jinggang Wang,Weihong Cao,Huajun Zheng,Zhenghong Guo,Zhengping Fang,Peng Chen,Juan Li
A bio-based phosphonate 4-(7-((diphenylphosphoryl)oxy)-5-hydroxy-4-oxo-4H-chromen-3-yl)phenyl diphenylphosphinate (DPGE) was synthesized using diphenylphosphinic chloride and genistein. DPGE was used to modify the flame retardancy of poly(ethylene 2,5-furandicarboxylate-co-ethylene terephthalate) (PEFT20) containing 20 mol % 2,5-furandicarboxylic acid. PEFT20 containing 8 wt % DPGE displays a UL-94 V0 rating and a limiting oxygen index of 29.8 vol %. The flame retardant mode is the comprehensive effects of melting-away, gas phase, and condensed phase induced by DPGE. In addition, triglycidyl isocyanurate (TGIC) was incorporated to regulate the mechanical performance of PEFT20/DPGE. The flexural and impact strengths of PEFT20/DPGE are modified greatly. The coupling reactions between PEFT20 and TGIC increase the molecular weight and mechanical properties of PEFT20 blends. But, TGIC counteracts the melting-away effect caused by DPGE. Therefore, too much TGIC causes the decrease in flame retardancy.
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Scientific Reports
·
2019
·Vol. 9
·期 1
·1-5
·
IF 4.011
Mei Jianfeng,Chen Xiang,Liu Jianghua,Yi Yu,Zhang Yanlu,Ying Guoqing
Genistein is known to have multiple biological activities and has great potential for use as a preventative medicine and in disease treatment. Genistein can be extracted from plants, but also can be obtained from its glycoside form, sophoricoside, which is more abundant in some plants. Biotransformation by unpurified microbial enzymes has the advantage of low cost and is a preferred method for production of natural compounds. This study isolated a strain of Rhizopus oryzae that could produce β -glucosidase, which efficiently hydrolyzes sophoricoside into genistein, from an enrichment culture of the dried fruits of Sophora japonica . After the composition of enzyme-producing medium and biotransformation conditions were optimized, a genistein yield of 85.6% was obtained after 24 h in a shake-flask biotransformation at pH 7.0 using an initial substrate concentration of 1 g/L. The developed process provides an alternative method for production of genistein, and would be suitable for scale-up production in the pharmaceutical industry.
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CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
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2019
·
IF 0.931
Li-Ting NIU,Gen-Gen LI,Hai-Feng LI,Fan CUI,Jing ZHANG,Ying HUANG,Kai CHEN,Jian-Fu ZHANG,Wen-Fei LI,Wei-Lu LIU
Genistein is an important isoflavone that has been widely used to prevent blood disease and cancer. In this work, a novel genistein electrochemical sensor was developed based on the composite of molecularly imprinted polymer (MIP) and carboxylated multiwalled carbon nanotubes (cMWCNTs). The MIP layer was electropolymerizated on the cMWCNTs modified electrode using carbazole as functional monomer and genistein as template molecule. The morphology and electrochemical performance of MIP/cMWCNTs were characterized by scanning electron microscopy (SEM) and cyclic voltammetry (CV), respectively. A series of experimental conditions were optimized, including the pH value of supporting electrolyte, electropolymerization potential range, molar ratio of functional monomers to template molecules, numbers of cycle, accumulation potential and accumulation time. Under the optimal conditions, the resulting electrochemical sensor (MIP/cMWCNTs/GCE) showed high performance, such as high sensitivity and selectivity towards genistein, a wide linear range (0.02–7.00 μM) and a low limit detection of 0.006 μM ( S / N = 3). The electrochemical sensor was applied to determination of genistein in tablets and human urine samples with satisfactory recoveries (97.9%–102.8%), and the accuracy of the sensor was demonstrated with the HPLC method.
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Nanoscale Research Letters
·
2017
·Vol. 12
·期 1
·1-8
·
IF 2.833
Cai Limei,Yu Rufen,Hao Xi,Ding Xiangcui
In this study, novel folic acid-conjugated chitosan nanoparticle was formulated for specific delivery of bioflavonoid, Genistein (GEN), to the cervical cancer cells. The prepared GEN-loaded chitosan nanoparticles (GCN) and folic acid-conjugated GCN (FGCN) showed smaller size with a controlled drug release profile. FGCN exhibited enhanced internalization potential in HeLa cells than that of GCN. The specific internalization of FGCN was mainly due to the affinity of folic acid (FA) with FRs-α which is present in large numbers in HeLa cells. The results revealed that FGCN has a specific affinity towards HeLa cells that will contribute to the better treatment. Folic acid-tagged nanoformulations exhibited a superior cytotoxic effect compared to that of non-targeted formulations. Consistently, IC50 value of GEN decreased from 33.8 to 14.6 μg/ml when treated with FGCN after 24 h incubation. The apoptosis studies indicated that the FGCN nanoparticles were then either GCN or free GEN in terms of anticancer activity. Overall, results revealed that folate conjugation to the delivery system might have great effect on the survival of cervical cancers that will be beneficial for overall cancer treatment.
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TOXICOLOGY LETTERS
·
2021
·
IF 4.374
Xing Ma,Xiaowei Yu,Jialing Min,Xin Chen,Ren Liu,Xueqing Cui,Jing Cheng,Mingyong Xie,Patrick Diel,Xiaojuan Hu
Genistein (GEN) has been demonstrated to interfere with antitumor effects of cisplatin (CIS) in vitro . To analyze whether these findings are also relevant in vivo , we examined the effects of combined GEN and CIS treatment in an ovariectomized nude mouse breast cancer xenograft model. Tumor growth and markers for antitumor activity were determined after three weeks of treatment. Furthermore, the concentrations of GEN metabolites were measured in serum, liver, and xenograft tumor tissues using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Three weeks’ oral exposure to GEN at a dose of 5 mg kg −1 ·d -1 resulted in an average concentration of total GEN metabolite equivalent as high as 0.2729 nmol g −1 wet weight in xenograft tumor tissues. At this dosage, GEN significantly antagonized the antitumor effects of CIS. Mechanistically, GEN blocked both the inhibition of cell proliferation and induction of apoptosis triggered by CIS. Moreover, GEN concentrations in xenograft tumor tissues were found to be significantly higher than in serum and liver. In conclusion, our findings suggested that oral GEN exposure at a level comparable to dietary exposure in humans could interfere with CIS chemotherapy.
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Scientific Reports
·
2025
·Vol. 15
·期 1
·1-10
·
IF 3.9
Mo Fei,Hong Min,Chen Xiao,Wang Qiye,Dong Chao
The accumulation of regulatory T cells (Tregs) in the tumor microenvironment is a key factor for immunosuppression and immune escape of cancer cells. Genistein is a natural isoflavonoid in soybeans, possessing a wide range of pharmacological bioactivities. However, the immunomodulatory potential of genistein remains largely unexplored. This study investigated the synergistic efficacy of genistein with anti-PD-1 therapy in a mouse model of melanoma. The regulatory role of genistein in Treg differentiation and functional stability was also examined in this study. The antitumor effects of genistein, alone or in combination with anti-PD-1 therapy, were evaluated in the mouse B16-F10 melanoma model. The profiles of intratumoral Tregs and CD8 + cytotoxic T cells were profiled using flow cytometry. The impact of genistein on the suppressive function and differentiation of Tregs was also studied in vitro. RT-qPCR, Western blotting and flow cytometry were conducted to characterize the functional phenotype of Tregs under genistein treatment. Genistein showed a synergistic effect with anti-PD-1 therapy in B16-F10 melanoma models, achieving enhanced immune infiltration and functional reprogramming of the tumor microenvironment. This combinatorial strategy not only reduced intratumoral Tregs but also elevated the CD8 + /Treg ratio. At the mechanistic level, genistein effectively suppressed critical Treg surface markers, which are indispensable for Treg-mediated immunosuppression. Furthermore, it disrupted Treg differentiation by attenuating PI3K/AKT signaling phosphorylation. Our data demonstrated that genistein boosts the antitumor effect of anti-PD-1 therapy by impairing the immunosuppressive function and differentiation of Tregs, indicating that genistein has the potential to enhance the treatment outcome of the immune checkpoint inhibitor.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
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IF 8.2
Lijuan Shi,Zhen Lin,Jiantong Hou,Wenhui Liu,Jing Xu,Yuanqiang Guo
Genistein is an isoflavone with chemopreventive and therapeutic effects on various types of cancers. Apparently, in contrast to the advantages of multi-target therapy, the poor water solubility of this molecule is a major obstacle to its clinical application. In this work, zein/chicory polysaccharide nanoparticles (G-zein-P NPs) were prepared by pH-induced antisolvent precipitation method for the encapsulation of genistein. Firstly, an acidic polysaccharide (CIP70-2) with a molecular weight of 66.7 kDa was identified from the roots of chicory ( Cichorium intybus ). This natural macromolecule was identified as a plant pectin, for which the structure included RG-I (rhamnogalacturonan I) and HG (homogalacturonan) regions. Using this polysaccharide, G-zein-P NPs were prepared, in which the water solubility of genistein was improved by encapsulation. The encapsulation efficiency and loading efficiency of genistein by composite nanoparticles reached 99.0 % and 6.96 %, respectively. In vitro tumor inhibition experiments showed that the inhibitory effect of G-zein-P NPs on HepG2 cells was twice that of unencapsulated genistein. Moreover, the significant inhibition of tumor development and metastasis by G-zein-P NPs was observed in zebrafish xenograft models. The results suggested that zein/chicory polysaccharide nanoparticles may be a promising delivery carrier for genistein application in cancer prevention and therapy.
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Scientific Reports
·
2021
·Vol. 11
·期 1
·1-10
·
IF 4.38
Xie Ziqi,Luo Yunjing,Na Zhen,Zhang Wei,Zong Yufei
In this study, a novel method based on genistein magnetic molecularly imprinted polymers (Gen-MMIPs) was developed utilizing a surface molecular imprinting technique, in which genistein was used as the template molecule and Fe 3 O 4 was used as the carrier. The synthesis of Gen-MMIPs was characterized by using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), which indicated that the diameter of the Gen-MMIPs was approximately 500 nm. Via analysis with a vibrating sample magnetometer (VSM), the saturation magnetization of Gen-MMIPs was determined to be 24.79 emu g −1 . Fourier transform infrared (FT-IR) spectroscopy showed that polymer groups were on the surface of the magnetic carrier. Adsorption experiments suggested that the genistein adsorption capability of Gen-MMIPs was 5.81 mg g −1 , and adsorption equilibrium was achieved within 20 min. Gen-MMIPs as dispersive solid-phase extraction (dSPE) adsorbents combined with HPLC were used to selectively separate genistein in soy sauce samples, and the recoveries ranged from 85.7 to 88.5% with relative standard deviations (RSDs) less than 5%, which proved that this method can be used for the detection of genistein residues in real samples.
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