Journal of Functional Foods
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2015
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IF 3.574
Shang-Ta Wang,Ting-Fang Fang,Chen Hsu,Chia-Hao Chen,Chun-Jung Lin,Nan-Wei Su
Research has indicated the health beneficial effects of soyfoods. Genistein, one of the primary bioactive agents in soybeans, has a number of pharmacological and biological activities; however, its low water solubility and low intestinal permeability may lead to the depletion of genistein absorption from dietary intake and contribute to its poor oral bioavailability. Previous study revealed a water-soluble phosphate conjugate of genistein, genistein 7-O-phosphate (G7P), generated by biotransformation of Bacillus subtilis var. natto BCRC80517 with genistein. This study aimed to investigate the dissolution profile, intestinal permeability and oral bioavailability of genistein and G7P. G7P improved water solubility and also enhanced intestinal permeability in vitro and in situ , and greatly increased plasma exposure to genistein after oral administration in rats. The aqueous solubility of genistein is the absorption barrier to its oral bioavailability. G7P may be a promising and efficient alternative to genistein.
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FOOD AND CHEMICAL TOXICOLOGY
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2026
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IF 3.2
Ruo Du,Qingyuan Li,Yi Cheng,Yuting Zeng,Mairewulan Abula,Wenyi Liu,Fangfang Yu,Weihua Jia,Yuhui Du,Yue Ba,Yanjie Wang,Guoyu Zhou
Zearalenone (ZEA), a mycotoxin produced by Fusarium fungi, has drawn significant attention due to its multi-organ toxicity. To explore the molecular mechanisms of ZEA-induced hepatotoxicity and identify effective intervention strategies, this study identified key targets associated with ZEA-induced hepatotoxicity by screening public databases. Further construction of a protein interaction network revealed five crucial targets: TP53 , STAT3 , HSP90AA1 , ESR1 , and PPARG . Moreover, genistein (GEN) was identified from the TCMSP database as a compound capable of simultaneously targeting these targets. Molecular docking results indicated that GEN exhibits strong binding affinity with the five targets (all binding energies <0 kcal/mol). To validate hepatotoxicity mediated by ZEA and intervention mechanisms of GEN, ZEA exposure and ZEA + GEN treated mouse models were conducted. The results exhibited that exposure to ZEA led to increased liver weight and liver coefficient as well as abnormal changes in typical hepatotoxicity indicators in mice, while GEN can alleviate the aforementioned changes. Furthermore, results from quantitative RT-PCR and Western blot indicated that hepatic Hsp90aa1 and HSP90α (the protein encoded by the Hsp90aa1 gene) expression was significantly upregulated by ZEA but significantly downregulated after GEN supplementation. In conclusion, HSP90α may be a key regulatory node in GEN treatment of hepatotoxicity caused by ZEA. Download: Download high-res image (558KB) Download: Download full-size image
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INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION
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2013
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IF 1.257
Hui Cao,Xiaohui Jing,Donghui Wu,Yujun Shi
Methylation of flavonoids appears to be a simple and effective way to improve metabolic resistance and transport of flavonoids. Serum albumins are major soluble proteins serving as transport proteins for many exogenous compounds. This work in here mainly concerns about the effect of methylation of flavonoids on the affinity for human serum albumin (HSA) and ovalbumin. One isoflavone (genistein) and one flavonol (kaempferol) and their monomethylated derivatives at position 4′ (biochanin A and kaempferide) were studied for their affinities for ovalbumin and HSA. The methylation of flavonoids significantly affects the binding process. In general, the methylation of flavonoids improved the affinities for proteins by 2–16 times. This result supports that the methylation of genistein and kaempferol enhanced the transporting ability, which leads to facilitated absorption and greatly increased bioavailability. The methylation increases the hydrophobicity of genistein and kaempferol, and the hydrophobic interaction plays an important role in binding flavonoids to HSA and ovoalbumin.
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
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2015
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IF 2.96
Suyun Lin,Guowen Zhang,Junhui Pan,Deming Gong
Genistein (Gen), widely distributed in soybean, is proved to be important in homeostasis in the human body. Herein, the inhibitory mechanism of Gen against xanthine oxidase (XO) was studied through multispectroscopic methods and molecular simulation. The inhibition kinetics showed that Gen competitively inhibited XO with an inhibition constant of (1.39 ± 0.11) μM by competing with xanthine for binding to the active site of XO. Fluorescence titration study suggested that the fluorescence quenching mechanism of XO was static, resulting from the formation of a Gen–XO complex at one fold site. The calculated thermodynamic parameters revealed that the interaction process was driven mainly by hydrophobic interactions and hydrogen bonds with affinity of (5.24 ± 0.02) × 10 4 L mol − 1 . Conformational analyses demonstrated that the microenvironment and the secondary structure of XO were changed upon binding of Gen. The molecular docking displayed that Gen bound to the active cavity of XO by interacting with the surrounding amino acid residues (Leu648, Phe649, Glu802, Ser876, Glu879, Arg880, Phe914, Phe1009, Thr1010 and Phe1013). Thus, the inhibition may be attributed to the insertion of Gen into the active site of XO occupying the catalytic center of the enzyme to avoid entry of the substrate and inducing conformational changes of XO (more compact), which was further unfavorable for forming the active cavity and further reduced the landing and oxidation of substrate. This study may offer novel insights into the inhibition mechanism of Gen on XO.
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Oncotarget
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2017
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IF 5.168
Hao Gu,Wei Wu,Beilei Yuan,Qiuqin Tang,Dan Guo,Yiqiu Chen,Yankai Xia,Lingqing Hu,Daozhen Chen,Jiahao Sha,Xinru Wang
Genistein (GEN) is one of the isoflavones that has effect on male reproduction. However, the underlying mechanism remains unknown. miRNAs are a type of small non-coding RNAs that play important roles in spermatogenesis. We measured the GEN levels and miR-17-92 cluster expression in infertile subjects and found that miR-17-92 might be involved in GEN induced abnormal spermatogenesis. To clarify, we fed adult ICR mice with different doses of GEN (0, 0.5, 5, 50 and 250 mg/kg/day) for 35 days to study the underlying mechanism. We found that sperm average path velocity, straight-line velocity and eurvilinear velocity of the mice orally with GEN at 5mg/kg/day were significantly decreased, the expression levels of miR-17 and miR-20a in mice testis were higher in corresponding group. We also found miR-20a was the only miRNA that differentially expressed both in human and mice. By applying bioinformatics methods, Limk1 was predicted to be the target gene of miR-20a that is involved in spermatogenesis. Limk1 were significantly decreased in the corresponding group. Dual-luciferase report assay also proved that miR-20a could directly target Limk1. These results implied that Limk1 might be the target gene of miR-20a that is involved in GEN induced abnormal spermatogenesis.
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CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
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2018
·Vol. 47
·期 4
·1667-1681
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IF 5.5
Lan Ying,Li Xiulian,Liu Xuebo,Hao Cui,Song Ni,Ren Sumei,Wang Wei,Feng Ningchuan,Zhang Lijuan
Background/Aims: Genistein is a natural isoflavone enriched in soybeans. It has beneficial effects for patients with mucopolysaccharidose type III through inhibiting glycosaminoglycan biosynthesis. However, other studies indicate that genistein does not always inhibit glycosaminoglycan biosynthesis. Methods: To understand the underlying molecular mechanisms, CHOK1, CHO3.1, CHO3.3, and HCT116 cells were treated with genistein and the monosaccharide compositions and quantity of all glycans from the cell lysate were measured after thorough acid hydrolysis followed by HPLC analysis. In addition, the glycosaminoglycan disaccharide compositions were obtained by stable isotope labeling coupled with LC/MS analysis. Results: Genistein treatment reduced the amount of glycans but increased the amount of glycosaminoglycans in HCT116 cells. In contrast, genistein treatment reduced both glycan and glycosaminoglycan quantities in CHOK1, CHO3.1, and CHO3.3 cells in addition to differential changes in glycosaminoglycan disaccharide compositions. Conclusion: Genistein treatment reduced overall glycan quantity but glycosaminoglycan quantities were either increased or decreased in a cell type-dependent manner
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PHYTOMEDICINE
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2026
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IF 11.3
Jieli Pan,Jinjun Ji,Xingpan Xin,Yihong Gan,Zixin Huang,Jing Chen,Ying Li,Jie Bao,Yujun Tang,Chengping Wen,Li Xu
Background Systemic lupus erythematosus (SLE) is an autoimmune disease with marked female predominance. Lupus nephritis (LN), one of its most severe manifestations, is strongly associated with aberrant activation of signal transducer and activator of transcription 3 (STAT3). Estrogen receptor β (ERβ) has been reported to exert immunoregulatory effects, but its role in restraining STAT3 signaling in LN remains unclear. Purpose This study aimed to investigate whether genistein, a phytoestrogen with selective affinity for ERβ, can modulate the ERβ–STAT3 axis to attenuate lupus nephritis. Methods The therapeutic effects of genistein were evaluated in MRL/lpr and pristane-induced lupus mouse models and in LPS-stimulated macrophages. Macrophage polarization, oxidative stress, mitochondrial function, and ERβ–STAT3 signaling were assessed using flow cytometry, biochemical assays, immunoblotting, and bioinformatic analyses. Results Genistein significantly ameliorated renal injury, reduced proteinuria, and decreased serum autoantibody and IL-6 levels in lupus models. Mechanistically, genistein suppressed M1 macrophage polarization by activating ERβ and inhibiting STAT3 and NF-κB signaling. Genistein also attenuated oxidative stress by preserving mitochondrial membrane potential, reducing reactive oxygen species production, and restoring antioxidant capacity. Pharmacological blockade of ERβ markedly attenuated the anti-inflammatory effects of genistein, confirming ERβ-dependent regulation of STAT3 signaling. Conclusion This study identifies ERβ as a negative regulator of STAT3-driven inflammation and demonstrates that genistein therapeutically engages this axis to suppress macrophage-mediated renal injury, offering a promising therapeutic strategy for lupus nephritis.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
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IF 6.7
Yi Kuang,Cailing Tan,Xianrui Tan,Jian Zhang
Isoflavones from legumes, particularly genistein, are highly valued as functional food ingredients. However, the poor water solubility and low bioavailability hinder its application, which can be improved through glycosylation. The glycosyltransferase GT2419 from Bacillus subtilis ATCC 6633 catalyzes the 7-OH and 4′–OH glycosylation of genistein, but its poor regioselectivity hampers the efficient synthesis of genistein 7-O-glucoside. Here, a semirational design strategy was employed to obtain the F231V mutant, which significantly increased the conversion rate of genistein 7-O-glucoside from 21.1% to 72.2% and improved the 7-O regioselectivity to 73.8%. Kinetic analysis revealed that the F231V mutant exhibited enhanced affinity and catalytic efficiency toward genistein. Computational analysis revealed that the F231V mutant enlarged the substrate-binding pocket and disrupted intermolecular hydrophobic interactions, thereby altering substrate orientation, and enhancing the regioselective formation of genistein 7-O-glucoside. This study provides an efficient biosynthetic method for genistein 7-O-glucoside, with promising applications in the food industry.
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Food & Function
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2021
·Vol. 13
·期 3
·1393-1407
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IF 5.396
Liuming Xie,Zhibing Huang,Hui Meng,Zhibing Fan,Xiaoyi Shi,Jianhua Xie
Manipulating the structures, physicochemical properties, and monosaccharide compositions of exopolysaccharides (EPS) isolated from microorganisms has been reported to enhance their biological activities. Hence, the aim of this work was to examine the effects of genistein addition during fermentation on the amount, physicochemical properties, and immunomodulatory activity of EPS secreted by M. purpureus. Results showed that genistein addition significantly increased M. purpureus biomass and EPS yield to 2.42 g L−1 and 6.08 g L−1, respectively, and affected the physicochemical properties and structures of EPS. Furthermore, EPS produced by genistein-treated M. purpureus (G-EMP) improved the immunomodulatory activity of RAW264.7 macrophages by increasing the secretion of nitric oxide and cytokines. Moreover, phospho-Jun N-terminal kinase (p-JNK), phospho-extracellular regulated protein kinase (p-ERK), phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) phospho-p65 (p65) proteins were remarkably upregulated by G-EMP stimulation, blocking Toll-like receptor 4 (TLR4) that dramatically reduced the pinocytic and phagocytic capacities. Overall, these findings provide potential rationales for the application of genistein in improving the EPS yield of M. purpureus.
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International Journal of Analytical Chemistry
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2026
·Vol. 2026
·期 1
·6094234
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IF 2.8
Amna Naz,Muhammad Farooq,Muhammad Sarfraz,Ahsanullah Unar,Rouheena Shakir,Hafiz Arfat Idrees,Nadia Anwar
Oleanolic acid (OL) and genistein (GN) are bioactive compounds known for their anti-inflammatory, antioxidant, antiviral, cardioprotective, and anticancer properties. Their synergistic therapeutic potential motivated the development of a hybrid nanoformulation, comprising GN nanoparticles incorporated into an OL-loaded liposomal system named GOL. The formulation was extensively characterized for particle size, polydispersity index, zeta potential, entrapment efficiency, and pharmacokinetic behavior, demonstrating its suitability for co-delivery of both drugs. To accurately quantify OL and GN in the GOL system, a robust HPLC-UV method was developed and validated. Simultaneous determination was challenging due to distinct chemical and spectral properties; OL showed λmax at 210–215 nm, while GN had λmax at 215, 270, and 336 nm. Optimization using a Box–Behnken design yielded a method using a C18 column with a methanol–acetonitrile–water–tetrahydrofuran (60:20:8:12, v/v) mobile phase and detection at 230 nm. Retention times were 4.8 and 9.9 min for OL and GN. Plasma samples were processed via simple protein precipitation. The method met ICH validation criteria for sensitivity, selectivity, accuracy, precision, robustness, and stability. Finally, the developed method was successfully applied to analyze both drugs from the GOL nanoformulation in both biological fluids and polymeric matrices, enabling a reliable assessment of drug content and stability.
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Current Research in Food Science
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2022
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IF 6.269
Liuming Xie,Gang Wang,Jianhua Xie,XianXiang Chen,Jiayan Xie,Xiaoyi Shi,Zhibing Huang
The exopolysaccharides (EPS) produced by the edible medicinal fungus Monascus purpureus (EMP) become the center of growing interest due to their techno-functional properties and their numerous applications in the food industries; however, the low EPS yields limit its application. In this study, the effect of genistein supplementation on the production, rheological and antioxidant properties of EPS by M . purpureus and its biosynthesis mechanism were explored. The results indicated that the addition of genistein (3 g/L) generated a 110% and 59% increase in the maximum mycelial biomass and EPS yield, respectively. The genistein supplementation group (G-EMP) had higher molar percentages of Xyl and Man, and significantly decreased molecule weight and particle size of EPS, which resulted in stronger antioxidant effect and cell growth promotion. Rheological analysis showed that both EMP and G-EMP demonstrated pseudoplastic fluid behavior and G-EMP exhibited strong gel-like elastic behavior (G' > G"). Furthermore, genistein not only facilitated the production of EPS by regulating cell membrane permeability, enhancing cellular respiratory metabolism and monosaccharide precursor synthesis pathways, and enhancing antioxidant enzyme activity to reduce oxidative stress damage, but also affected the composition of the monosaccharides by increasing enzyme activity in the underlying synthesis pathways. These findings expand the application of M . purpureus resources and provide a paradigm for future study of the structural and functional characteristics of EPS.
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International Journal of Nanomedicine
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2024
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IF 6.6
Rui Gao,Peihong Lin,Wenjing Yang,Zhengyu Fang,Chunxiao Gao,Bin Cheng,Jie Fang,Wenying Yu
Background Genistein (Gen), a natural polyphenolic compound, has emerged as a promising candidate for lung cancer treatment. However, the potential clinical application of Gen is limited due to its poor solubility, low bioavailability, and toxic side effects. To address these challenges, a biomimetic delivery platform with cell membranes derived from natural cells as carrier material was constructed. This innovative approach aims to facilitate targeted drug delivery and solve the problem of biocompatibility of synthetic materials.Methods First, the liposomes (LPs) loaded with Gen (LPs@Gen) was prepared using the ethanol injection method. Subsequently, PLTM-LPs@Gen was obtained through co-extrusion after mixing platelet membrane (PLTM) and LPs@Gen. Additionally, the biological and physicochemical properties of PLTM-LPs@Gen were investigated. Finally, the targeting ability, therapeutic efficacy, and safety of PLTM-LPs@Gen for lung cancer were evaluated using both a cell model and a tumor-bearing nude mouse model.Results The optimal preparation ratio for LPs@Gen was Gen: soybean lecithin: cholesterol: DSPE-PEG2000 (3:30:5:10, mass ratio), while the ideal fusion ratio of LPs@Gen and PLTM was 1:1. The particle size of PLTM-LPs@Gen was 108.33 ± 1.06 nm, and the encapsulation efficiency and drug loading were 94.29% and 3.09% respectively. Gen was released continuously and slowly from PLTM-LPs@Gen. Moreover, PLTM-LPs@Gen exhibited good stability within one week. The results of in vitro cellular uptake and in vivo distribution experiments indicated that the carrier material, PLTM-LPs, has the immune escape ability and tumor targeting ability. Consequently, it showed better therapeutic effects than free drugs and traditional LPs in vitro and in vivo tumor models. In addition, safety experiments demonstrated that PLTM-LPs@Gen possesses good biocompatibility.Conclusion Biomimetic nanomedicine provides a new strategy for the precision treatment of lung cancer in clinical practice.
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