Pharmaceutics
·
2024
·Vol. 16
·期 3
·306
·
IF 4.9
Chenxu Qiu,Yancui Zhang,Yingsai Fan,Shupeng Li,Jianting Gao,Xin He,Xinghua Zhao
Genistein (GEN) is an active pharmaceutical ingredient that presents the challenges of poor water solubility and low oral bioavailability. To tackle these challenges, a GEN solid dispersion was prepared by solvent rotary evaporation using polyvinylpyrrolidone K30 (PVP K30) as a carrier. The optimal formulation was determined by drug loading efficiency and in vitro release. The physical state of the solid dispersion was characterized by DSC, XRD, SEM and FT-IR. And the results of the in vitro release study indicate that the drug release of SD (1:7) increased 482-fold that of pure GEN at 60 min. Following oral administration to rats, the Cmaxand AUC0–24of SD (1:7) was increased 6.86- and 2.06-fold to that of pure GEN. The adipose fat index and body weight of the SD (1:7) group were significantly lower than those of the GEN group (p< 0.05). Meanwhile, the levels of TC and TG in the serum were significantly decreased in the SD (1:7) group compared with the GEN group (p< 0.05). All experiments revealed that solid dispersion could be a promising formulation approach to improve the dissolution rate, oral bioavailability, and effect on the reduction of lipid accumulation in high-fat diet-induced obesity mice.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
·
IF 6
Yu Zhang,Na Zhang,Yingsai Fan,Yanling Sun,Xin He,Xinghua Zhao
A food-grade nanosized genistein solid dispersion with superior mucus-penetrating property was successfully fabricated. • GEN-SD improves intestinal absorption via paracellular diffusion, clathrin-mediated endocytosis and low BCRP efflux. • The integrated SPIP–mucus–Caco-2 model provides a universal strategy for poorly soluble nutraceuticals. Genistein (GEN) is a typical soy-derived nutraceutical ingredient with multiple health-promoting bioactivities, but its application is severely limited by poor solubility and low oral bioavailability. In this study, the intestinal absorption behavior, transport pathways, and underlying mechanisms of GEN, its physical mixture (GEN-PM) and genistein solid dispersion (GEN-SD) were systematically investigated using a combined strategy including rat in situ single-pass intestinal perfusion (SPIP), mucus penetration evaluation and Caco-2 cell monolayer model. The prepared GEN-SD presented a particle size of only 100.11 nm and a BET specific surface area of 8.46 m 2 /g, which was 59.7% smaller and 130.5% larger than raw GEN respectively. SPIP results showed that GEN-SD exhibited significantly higher effective permeability coefficient ( P eff ) and absorption rate constant ( K a ) in the duodenum at pH 7.4 and 10 μg/mL ( P < 0.05). Removal of the intestinal mucus layer markedly reduced the absorption advantage of GEN-SD ( P < 0.05), and in vitro Transwell assay verified its superior mucus-penetrating ability, with the 240 min cumulative transport quantity of GEN-SD increased by 26.04% and its Papp value elevated by 24.15% compared with pure GEN. In Caco-2 monolayers, GEN-SD displayed significantly enhanced time-dependent bidirectional transport and apparent permeability ( P app ) ( P < 0.05), and CLSM confirmed stronger intracellular uptake. Inhibitor studies in both SPIP and Caco-2 models demonstrated that the absorption of GEN-SD was prominently inhibited by EDTA and chlorpromazine hydrochloride ( P < 0.05), indicating involvement of paracellular diffusion and clathrin-mediated endocytosis, while reserpine showed no significant effect, suggesting minimal BCRP-mediated efflux. The superior absorption of GEN-SD was attributed to the synergistic effects of amorphization, nanoscale particle size, enlarged specific surface area, improved mucus penetration, enhanced paracellular diffusion and clathrin-mediated endocytosis. This study provides a mechanistic basis for developing oral delivery systems with improved bioavailability for genistein. Download: Download high-res image (163KB) Download: Download full-size image
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Kunshan Wang,Yingao Zhai,Zenghui Yu,Xuan Zhang,Suzhen Zhou,Jinbo Fan
To mitigate postprandial hyperglycemia, acarbose's excessive α-amylase (AMY) inhibition causes gastrointestinal side effects. Baicalein (Bai), genistein (Gen), and isoliquiritigenin (Isl), featuring 5,6-dihydroxyflavone structures, mildly inhibit AMY. In this study, the inhibitory mechanism of Bai, Gen, and Isl on AMY was determined by integrating multiple analytical techniques and molecular simulation technologies. The results showed that Bai/Gen/Isl exhibited strong inhibitory activity against AMY with IC 50 values of 22.44 ± 0.92 μmoL·L −1 , 24.78 ± 1.91 μmoL·L −1 , and 26.78 ± 1.79 μmoL·L −1 , respectively, which belonged to the mixed inhibition type dominated by competitive inhibition. The three form a ground state complex with AMY through a static quenching mechanism, and the order of binding constants is Bai > Gen > Isl. Their binding significantly changed the microenvironment polarity of Trp residues in AMY and induced secondary structure rearrangement. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) showed that the relative crystallinity of AMY increased, forming dense aggregates and increasing thermal stability. Molecular simulation showed that the interactions between AMY and Bai/Gen were dominated by van der Waals forces or hydrogen bonds, while the interactions with Isl were dominated by hydrophobic interactions. By employing a novel integrative approach combining fluorescence/UV–Vis/FTIR spectroscopy, DSC-XRD-SEM characterization, and 120 ns molecular dynamics simulation, this study overcomes the single-technique limitations of previous research and provides a theoretical basis for the development of blood glucose control agents based on natural products.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 54
·31201-31212
·
IF 2.936
Xiaokang Long,Yao-Fu Zeng,Yunmei Liu,Ying Liu,Tangluo Li,Lanqing Liao,Yu Guo
Genistein amino acid derivatives 4a–4d were synthesized and evaluated for their cytotoxic activities against MCF-7, Hela, MGC-803 and HCT-116 cell lines by MTT assays in vitro. The results revealed that compounds 4a–4d showed better activity than the parent compound genistein. Particularly, compound 4b displayed the most significant anticancer activity against MGC-803 with an IC50 value of 12.08 μM. In addition, the mechanisms of interaction between genistein, compounds 4a–4d and BSA were investigated via multi-spectroscopic techniques such as ultraviolet (UV) spectroscopy, fluorescence, circular dichroism (CD), and molecular docking under physiological conditions. The results suggested that endogenous fluorescence of BSA could be quenched by genistein and compounds 4a–4d via forming BSA-compound complex, which meant a static quenching mechanism was involved. The negative values of enthalpy (ΔH) and entropy (ΔS) indicated that interactions between BSA and the ligands were spontaneous, and hydrogen bonding and van der Waals interactions were involved in the BSA-compound complexion formation. The UV, synchronous and 3D fluorescence results revealed that the micro-environment of tryptophan and conformation of BSA were changed after binding to ligands. CD analysis demonstrated the variation in the secondary structure and that the α-helix content of BSA decreased. Eventually, molecular docking was executed to forecast the binding forces and binding sites between BSA and compounds 4a–4d.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2024
·
IF 5.7
Chen Siwei,Huang Hongwu,Li Qi,Cai Jia,Miao Zhuolin,Xie Peikang,Tang Shengsong,He Dongxiu
5-Fluorouracil (5-FU) is commonly used as a chemotherapeutic drug for advanced HCC. However, the effectiveness of 5-FU is limited by the emergence of resistance and poor targeting efficiency. Combining 5-FU with natural compounds has shown promise in HCC treatment. In this study, we prepared carrier-free nanoparticles (GEN-Cu-GEN@FUA) containing 5-FU and genistein (GEN) in a synergistic ratio via a green synthesis procedure. The resulting GEN-Cu-GEN@FUA nanoparticles had a spherical or near spherical shape, a dynamic size of 129.3 ± 40.1 nm, and a high drug loading content of approximately 21.40% (5-FU) and 61.48% (GEN). These nanoparticles exhibited approximately 3.6-fold lower IC50 value than 5-FU alone in Bel-7402 cells and resulted in a 3.7-fold greater reduction in tumor weight compared to 5-FU alone in Bel-7402 tumor-bearing BALB/c mice. Importantly, the nanoparticles showed negligible systemic toxicity due to their synergistic effect on cancer cell dysfunction and significant amplification of intracellular glutathione consumption. Our findings suggest that the developed carrier-free nanomedicines offer a highly promising platform for the co-delivery of genistein (GEN) copper(II) complexes and 5-FU, with easy fabrication and great potential for clinical translation in HCC synergistic therapy. Graphical abstract
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Yu-Zhen Zhang,Yi-Le Li,Zhi Jin,Mao-Fang He,Yi-Mei Tang,Jian Zhang,Bo Zhang
Flemingia philippinensis Merr.et Rolfe ( F. philippinensis ) is an important food ingredient as well as a traditional Chinese medicine with numerous pharmacological actions. Unfortunately, there was no defined method for monitoring the quality of F. philippinensis in the Chinese Pharmacopoeia. In this study, a magnetic covalent organic framework molecularly imprinted polymers (MCOFs-MIPs) was prepared using MCOFs as a support material, genistein (Gen), which was abundant in F. philippinensis , as a template molecule, and acrylamide as a functional monomer. The preparation process of MCOFs-MIPs was optimized and their structures and adsorption characteristics were characterized. In the selectivity test, the imprinting factor of Gen was 1.93, demonstrating that the imprinting effect of MCOFs-MIPs could selectively enrich Gen in complex samples. Following that, a new and effective quality control method (Gen-MCOFs-MIPs-HPLC) was established to determine Gen content in F. philippinensis roots. The method showed good linearity (R 2 = 0.9936) in the range of 0.12–80 µg mL −1 . The recoveries of Gen in F. philippinensis high, medium and low samples were 90.5–91.0 %, 92.1–100.1 and 92.8–100.8, respectively. Stability and reproducibility tests revealed that this method was stable (RSD of 1.20 %) and reproducible (RSD of 0.70 %). Moreover, the calculation showed that the amount of Gen in the F. philippinensis powder was 0.4489 mg g −1 . As a result, the approach was shown to be simple, repeatable, and stable, and it provided a sensitive and reliable method for the extraction and detection of Gen in natural products.
✓ 已验证
产品关联
DOI
高影响因子
Advanced Composites and Hybrid Materials
·
2025
·Vol. 8
·期 1
·1-21
·
IF 21.8
Zhou Qiang,Shubhra Quazi T. H.,Lai Peng,Shi Jiayi,Fang Chenhao,Guo Qian,Li Wanqing,Chen Rui,Shen Xinkun,Huang Lina,Cai Xiaojun,Lin Sen
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a poor prognosis that is usually advanced at the time of diagnosis. Photodynamic therapy (PDT), with its safety and reproducibility, offers significant potential for advanced NPC treatment, though its efficacy is hindered by the hypoxic tumor microenvironment and continuous oxygen depletion during therapy. This study presents a versatile nanoformulation (CGP) co-loaded with chlorin e6 (Ce6) and genistein (Gen) within peptide dendritic nanogel (PDN) for enhanced NPC treatment. The positively charged CGP is efficiently internalized by NPC cells, followed by glutathione (GSH)-responsive degradation, releasing Ce6 and Gen. The released Gen reduces intracellular oxygen consumption and tumor metastability by inhibiting the HIF-1 signaling pathway, thereby efficiently boosting PDT efficacy. In vitro and in vivo studies confirmed that the combination of Gen and PDT effectively eliminates tumors and inhibits metastasis. Multi-omics analysis (RNA sequencing and targeted energy metabolomics) revealed that CGP suppresses HIF-1α, GLUT1, and VEGFA expression, downregulating the HIF-1 pathway and reducing anaerobic glycolysis, thereby successfully remodeling the hypoxia-associated tumor microenvironment. This study demonstrates that the Gen-PDT combination is a versatile approach capable of enhancing PDT efficacy and holds promise for NPC management.
✓ 已验证
产品关联
DOI
高影响因子
Antioxidants
·
2023
·Vol. 12
·期 1
·125
·
IF 7
Sai-Ya Zhang,Zi-Chen Qin,Yi-Yang Sun,Yu-Si Chen,Wen-Bo Chen,Hong-Gang Wang,Di An,Dan Sun,Yan-Qiang Liu
To determine the anti-heat stress and antioxidant effects of genistein and the underlying mechanisms, lipofuscin, reactive oxygen species (ROS), and survival under stress were first detected inCaenorhabditis elegans (C. elegans); then the localization and quantification of the fluorescent protein was determined by detecting the fluorescently labeled protein mutant strain; in addition, the aging-related mRNAs were detected by applying real-time fluorescent quantitative PCR inC. elegans. The results indicate that genistein substantially extended the lifespan ofC. elegansunder oxidative stress and heat conditions; and remarkably reduced the accumulation of lipofuscin inC. elegansunder hydrogen peroxide (H2O2) and 35 °C stress conditions; in addition, it reduced the generation of ROS caused by H2O2and upregulated the expression ofdaf-16,ctl-1,hsf-1,hsp-16.2,sip-1,sek-1,pmk-1, andeat-2, whereas it downregulated the expression ofage-1anddaf-2inC. elegans;similarly, it upregulated the expression ofdaf-16,sod-3,ctl-1,hsf-1,hsp-16.2,sip-1,sek-1,pmk-1,jnk-1 skn-1, andeat-2, whereas it downregulated the expression ofage-1,daf-2,gst-4, andhsp-12.6inC. elegansat 35 °C; moreover, it increased the accumulation of HSP-16.2 and SKN-1 proteins in nematodes under 35 °C and H2O2conditions; however, it failed to prolong the survival time in the deleted mutant MQ130 nematodes under 35 °C and H2O2conditions. These results suggest that genistein promote anti-heat stress and antioxidant effects inC. elegansvia insulin/-insulin-like growth factor signaling (IIS), heat shock protein (HSP), mitogen-activated protein kinase (MAPK), dietary restriction (DR), and mitochondrial pathways.Keywords:genistein;anti-heat stress;antioxidant;Caenorhabditis elegans
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of the Mechanical Behavior of Biomedical Materials
·
2021
·
IF 3.902
Shulin Luo,Pei Wang,Min Ma,Zhangyi Pan,Liangyu Lu,Feng Yin,Junfeng Cai
Poly(ether-ether-ketone) (PEEK) with good biocompatibility exhibits high mechanical strengths but bioinert. In addition, tantalum (Ta) possesses outstanding osteogenesis but high density and elastic modulus , and cost. In this study, by blending Ta nanoparticles with PEEK, Ta/PEEK composite (TP) was prepared, which was then treated by concentrated sulfuric acid to form a microporous surface containing Ta particles on TP (TPS). Moreover, genistein (GS) with antibacterial property was loaded into the microporous surface of TPS (TPSG). Compared with TP, the surface properties ( e.g., surface roughness and hydrophilicity) of TPS was obviously improved because of the microporous surface including Ta nanoparticles . Moreover, TPS showed low antibacterial properties because of presence of sulfonic group while TPSG exhibited excellent antibacterial properties due to GS loaded into the microporous surface. Furthermore, compared with TP, TPS obviously promoted attachment and proliferation of MG63 cells, while TPSG with GS remarkably inducing osteogenic differentiation of the cells compared with TPS in vitro . Moreover, in comparison with TP, TPS with optimized surface properties promoted new bone regeneration and osseointegration, while TPSG loading GS further enhanced bone regeneration as well as osseointegration in vi vo. In summary, the GS loaded into microporous surface including Ta nanoparticles of TPSG exhibited antibacterial and osteogenic activity, which would have great potential for bone tissue repair.
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 9
·期 1
·167-185
·
IF 6.183
Shiqi Mei,Fan Wang,Xinglong Hu,Kong Yang,Dong Xie,Lili Yang,Zhaoying Wu,Jie Wei
Nanoporous tantalum pentoxide (NTP) particles with a pore size of about 10 nm were synthesized and blended with polyetheretherketone (PEEK) to fabricate a PEEK/NTP composite (PN). Subsequently, PN was treated by concentrated sulfuric acid to create a microporous surface (pore size of around 2 μm) on sulfonated PN (SPN), which formed a hierarchical micro & nanoporous surface. Compared with PN, the porous surface of SPN exhibited higher roughness, hydrophilicity, and surface energy. In addition, genistein (GT) was loaded into the porous surface of SPN (SPNG), which showed high GT loading capacity and sustained release of GT into phosphate buffered saline (PBS). Moreover, SPNG revealed excellent antibacterial activity, which inhibited bacterial (E. coli and S. aureus) growth in vitro due to the synergistic effects of both sulfonic acid (SO3H) groups and the sustained release of GT. Compared with PN, SPN significantly improved the adhesion, proliferation, and osteogenic differentiation of bone mesenchymal stem cells in vitro. Moreover, compared with SPN, SPNG further enhances the cell responses. Compared with PN, SPN remarkably improved bone formation and osteointegration in vivo. Furthermore, compared with SPN, SPNG further enhanced the osteointegration. In short, SPNG with a micro & nanoporous surface, SO3H groups, and the sustained release of GT exhibited antibacterial activity and accelerated osteointegration, which would have tremendous potential as drug-loaded implants for bone substitute.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2020
·
IF 4.006
Shanshan He,Xin Liu,Yanling Wang,Jianhua Xie,Heng Gao,Xiujiang Li,Zhibing Huang
Monascus mold produces useful bioactive compounds such as Monascus pigments, monacolin K, and ergosterol . In this study, metabolomics analysis was used to investigate the metabolic profile changes in Monascus aurantiacus Li AS3.4384 (MALA) induced by genistein at different fermentation times using UHPLC-Q-TOF-MS/MS. The addition of genistein was found to not only reduce citrinin but also suppress significant differential metabolites. A total of 21 significant differential metabolites were involved in the most significant metabolic pathways (impact >0.1). These metabolites affected the aspartic acid , glutamic acid pathway, tricarboxylic acid (TCA) cycle, pyruvate synthesis pathway, and lysine degradation pathway. Thus, the addition of genistein may change the precursor for citrinin synthesis of Monascus . These findings provide significant insight into the Monascus metabolic pathways affected by genistein and will help to improve the quality control and safety of Monascus in food and supplements.
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2016
·Vol. 7
·期 11
·4683-4692
·
IF 2.686
Fan Yuan-jing,Wei Wei,Luo Jian-ping,Jin Yu-xia,Dai Zi-ling
This study aimed to explore the effects of genistein on regulating the activation of UGTs via the Nrf2/Keap1 pathway and to elucidate the underlying mechanisms of detoxification and hepatic protection. Experiments monitoring genistein-induced protection against acetaminophen-induced cell damage were performed in L-02, HepG2 and Hep3b cells. The results of the MTT, AST, ALT, LDH, GSH and GSSG assays showed that genistein evidently protected the cells from acetaminophen-induced injury in a dose-dependent manner. The control cells were treated with 10 mM acetaminophen without genistein to compare with the effects of the combination of acetaminophen and genistein on the expression of UGT1A1, 1A6 and 1A9, Nrf2 and Keap1 mRNAs, as well as the expression of Nrf2 and Keap1 proteins, which were tested by western blotting. The results showed that the expression of the Nrf2 mRNA and protein increased; in contrast, the expression levels of the Keap1 mRNA and protein were obviously reduced by genistein in a dose-dependent manner. Meanwhile, the expression of the UGT mRNA was increased, and UGT1A9 exhibited the highest expression among the three UGTs. Accordingly, the residual acetaminophen content was obviously reduced and acetaminophen glucuronidation increased after 24 hours of treatment with genistein in a dose-dependent manner.
✓ 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）