Toxicology Research
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2024
·Vol. 13
·期 1
·
IF 2.2
Zhang Chu,Liao Yupei,Li Tangjia,Zhong Haijing,Shan Luchen,Yu Pei,Xia Chenglai,Xu Lipeng
The 2022 US Cancer Statistics show that breast cancer is one of the most common cancers in women. Epidemiology has shown that adding flavonoids to the diet inhibits cancers that arise in particular women, such as cervical cancer, ovarian cancer, and breast cancer. Although there have been research reports on apigenin (API) and breast cancer, its anti-tumor effect and potential mechanism on breast cancer have not yet been clarified. Therefore, in this study, we used 4T1 cells and a 4T1 xenograft tumor mouse model to investigate the antitumor effect of API on breast cancer and its underlying mechanism. In vitro, we used MTT, transwell, staining, and western blotting to investigate the inhibitory effect of apigenin on 4T1 and the underlying molecular mechanism. In vivo by establishing a xenograft tumor model, using immunohistochemistry, and flow cytometry to study the inhibitory effect of apigenin on solid breast tumors and its effect on the tumor immune microenvironment. The results showed that API can induce breast cancer cell apoptosis through the PI3K/AKT/Nrf2 pathway and can improve the tumor immune microenvironment in mice with breast tumors, thereby inhibiting the growth of breast cancer. Thus, API may be a promising agent for breast cancer treatment.
研究领域:
肿瘤学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Shuang Xiao,Peng Zhang,Guowen Zhang,Wenwen Li,Haowen Lin,Xing Hu
The activation of toll-like receptor 4 (TLR4) signaling is crucial for initiating and coordinating the immune response against infections, and is proved as a vital target for inflammatory diseases. Herein, TLR4 with sufficient amount and functional activity was generated by heterologous expression and used to investigate the mechanism of apigenin (Api)/chrysin (Chr) inhibition of TLR4 activation. The results demonstrated that Api/Chr exhibited a strong fluorescence quenching effect through a static quenching and a high binding affinity ( K a > 10 5 L·mol −1 ) with TLR4, indicating the potential of Api/Chr as a TLR4 inhibitor. Additionally, the binding of Api/Chr induced a loose and unstable conformation of TLR4 with evidence like the decreased hydrophobicity of the tryptophan microenvironment, decreased α-helix content and increased free sulfhydryl content, resulting in reduced stability of the TLR4. The computer simulations revealed that Api/Chr occupied the myeloid differentiation factor 2 (MD-2) binding region, preventing MD-2 from binding to TLR4. Furthermore, the accuracy of the binding site between Api/Chr and TLR4 was confirmed through genetic mutations . Overall, the mechanism by which Api/Chr inhibited TLR4 activation was elucidated at the macroscopic and molecular levels, providing the worthful information concerning the future therapeutic application of Api/Chr as a natural TLR4 inhibitor.
研究领域:
免疫学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
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2020
·Vol. 29
·期 10
·1867-1873
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IF 1.783
Yang Xin-Bin,Huang Yu
The water-soluble sulfated derivatives, apigenin-8-sulfonate sodium (AS) and apigenin-3′, 8-disulfonate sodium (ADS) derived from parent apigenin (AP), were synthesized and characterized by infrared (IR) spectra, hydrogen nuclear magnetic resonance ( 1 H NMR), carbon nuclear magnetic resonance ( 13 C NMR), high-resolution mass spectra (HRMS), and elemental analysis. The mice model of hepatotoxicity induced by d -Galactosamine ( d -GalN) was used to evaluate the hepatoprotective effects of AP, AS, and ADS. The results indicated that AP, AS, and ADS could reduce the level of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic malondialdehyde (MDA) induced by d -GalN, and restore the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) toward normal levels. The histological results also suggested that AP, AS, and ADS could alleviate liver toxicity. The possible mechanisms could be ascribed to the protection role of AP, AS, and ADS, which kept hepatic cells from oxidative damage and maintain intracellular antioxidant enzyme activity. These findings uncovered that AP, AS, and ADS were able to protect liver from d -GalN-induced acute damage, and AS was the most potent hepatoprotective drug among the three compounds.
研究领域:
药理学
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肝病学
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生物化学
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高影响因子
JOURNAL OF CHEMICAL RESEARCH
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2013
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IF 0.596
Ji Zhang,Man Liu,Wei Cui,Jian Yang,Xia-li Liao
An efficient synthesis of apigenin using 1,3,5-trimethoxybenzene and anisaldehyde as starting materials is described, involving Friedel–Crafts acylation, selective demethylation, cyclisation, and demethylation. This transformation features a new method for the deprotection of methyl ethers. The overall yields reached approximately 55%.
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DOI
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Di Sun,Chunlei Cao,Feng Sun,Yifan Liu,Zihui Jin,Qiyang Zhao,Yue He,Yaohai Zhang,Yongliang Cui
Apigenin, a 4′,5,7-trihydroxyflavone compound with diverse biological activities, is found abundantly in vegetables and fruits, particularly in celery. The identification and quantification of apigenin have become critical indicators for quality control in raw pharmaceuticals, finished drugs, and formulations. This study established an indirect competitive enzyme-linked immunosorbent assay (icELISA) based on monoclonal antibodies for the quantitative detection of apigenin in celery. The method exhibited a median inhibitory concentration (IC 50 ) of 0.45 ng/mL, with a working range of 0.15 to 1.52 ng/mL (IC 20 -IC 80 ). It showed average recoveries of 83.6–113.7 % in celery leaf samples and 76.8–99.2 % in celery petiole samples. Moreover, the apigenin content in ten celery samples was determined using the developed icELISA and validated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). These results demonstrate that the established immunoassay is suitable for detecting apigenin in complex matrix samples, offering enhanced efficiency, sensitivity, and operational convenience compared to conventional analytical methods.
研究领域:
分析化学
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食品科学
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免疫学
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植物生物化学
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DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL RESEARCH
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2015
·
IF 0.633
Qian Wang,Wei Cui,Man Liu,Ji Zhang,Rong-qiang Liao,Xia-li Liao,Jian Yang
Two routes for the synthesis of the flavone apigenin are described. In the first, taxicatigenin was converted to 2-hydroxy-4,6-dimethoxyacetophenone and then by condensation with anisaldehyde to 2′-hydroxy-4,4′,6′-trimethoxychalcone. The latter was cyclised with iodine and demethylated with pyridine hydrochloride to form apigenin in 53% overall yield. In the second route, a single step for the preparation of the chalcone was used in which 1,3,5-trimethoxybenzene was acylated with p-methoxycinnamic acid. Although the synthesis of apigenin was achieved in a lower overall yield of 34%, the process was simpler.
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高影响因子
MOLECULES
·
2012
·Vol. 17
·期 12
·14748-14764
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IF 2.386
Rui Liu,Bin Zhao,Dong-En Wang,Tianyu Yao,Long Pang,Qin Tu,Jian-Jun Liu,Jinyi Wang
A series of nitrogen-containing apigenin analogs4a–jwas synthesized via Mannich reactions to develop anticancer, antibacterial, and antioxidant agents from plant-derived flavonoids. The chemical structures of these compounds were confirmed using1H-NMR,13C-NMR, and ESI-MS. Thein vitrobiological activities of the analogs were evaluated via assays of their antiproliferative, antibacterial, and antioxidant activities. The prepared apigenin analogs exhibited different antiproliferative activities against four human cancer cell lines, namely human cervical (HeLa), human hepatocellular liver (HepG2), human lung (A549), and human breast (MCF-7) cancer cells. Compound4ishowed the most favorablein vitroantiproliferative activity with IC50values of 40, 40, 223, and 166 μg/mL against HeLa, HepG2, A549, and MCF-7, respectively. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity assay also showed that4ihad the most potent antioxidant activity, with the smallest IC50value (334.8 μg/mL). The antibacterial activities of the analogs were determined using a two-fold serial dilution technique against four pathogenic bacteria, namelyStaphylococcus aureus,Bacillus subtilis,Escherichia coli, andPseudomonas aeruginosa. All the prepared apigenin analogs exhibited more potent activities than the parent apigenin. Compounds4hand4j, in particular, exhibited the best inhibitory activities against the Gram-positive bacteriaStaphylococcus aureusandBacillus subtiliswith MIC values of 3.91 and 1.95 μg/mL, respectively.Keywords:apigenin analogs;antiproliferative activity;antibacterial activity;antioxidant activity
研究领域:
药理学
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化学
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肿瘤学
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微生物学
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PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2023
·
IF 5.1
Honghui Liu,Puxin Huang,Xingchen Wang,Yufang Ma,Jing Tong,Jing Li,Hong Ding
This study investigated the inhibitory potential of a series of synthesized compounds (L1-L27) on α-glucosidase. Among them, compound L22 showed significant inhibitory effect. Through enzymatic kinetics studies, we demonstrated that L22 acts via a non-competitive inhibition mode with a K i value of 2.61 μM, highlighting its high affinity for the enzyme. Molecular docking studies revealed the formation of hydrogen bonds between L22 and α-glucosidase and diverse interactions with neighboring amino acid residues. Furthermore, molecular dynamics simulations confirmed the stability of the L22-α-glucosidase complex. In a mouse model of type 2 diabetes, treatment with L22 significantly lowered fasting blood glucose levels, and reduced insulin resistance, suggesting its potential as a therapeutic agent for type 2 diabetes. Furthermore, L22 showed a protective effect against oxidative stress in the liver and alleviated liver and pancreatic abnormalities. These results provide valuable insights into the mechanism of action of L22 and its potential applications to treat type 2 diabetes, and improve liver health.
研究领域:
药理学
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分子生物学
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代谢病研究
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DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2026
·Vol. 91
·期 7
·e71285
·
IF 4.1
Yu Zheng,Shiqin Wu,Yujia Sun,Li Zhou,Xiangmei Ren,Yuanhong Li,Fuxing Lin
Cronobacter sakazakii is a significant foodborne pathogen commonly associated with dairy products, causing severe infections with high mortality rates, particularly in neonates and immunocompromised adults. In this study, we demonstrated that apigenin exhibits potent antibacterial activity against C. sakazakii , with a minimum inhibitory concentration (MIC) of 160 mg/L. Propidium iodide staining indicated that apigenin at sub-MIC and MIC concentrations had negligible effects on bacterial membrane integrity; only a 4.9% increase in membrane permeability was observed at 2 MIC, suggesting that membrane damage is not the primary antibacterial mechanism. Further analysis revealed that apigenin treatment significantly reduced Adenosine triphosphate (ATP) levels within 2 h without altering growth kinetics or membrane integrity, indicating that ATP reduction resulted from metabolic disruption rather than cell death. Targeted metabolomics analysis revealed distinct separation in metabolic profiles between apigenin-treated and control groups, identifying 19 differential metabolites enriched in multiple pathways, with the citric acid (TCA) cycle being the most profoundly perturbed pathway. Biochemical assays confirmed that apigenin markedly decreased the activities of four key TCA cycle enzymes: isocitrate dehydrogenase (ICDHc, 40.09% reduction), α-ketoglutarate dehydrogenase (α-KGDH, 39.26% reduction), succinate dehydrogenase (SDH, 97.66% reduction), and malate dehydrogenase (MDH, 85.86% reduction). Molecular docking further supported the potential interaction between apigenin and these TCA cycle-related enzymes. Collectively, our findings suggest that apigenin inhibits C. sakazakii growth in association with the inhibition of key TCA cycle enzymes, which may contribute to the disruption of central carbon metabolism and ATP biosynthesis, ultimately leading to bacterial metabolic dysfunction and growth inhibition.
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PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 7
·2915
·
IF 4.6
Xueyan Ji,Wei Du,Wenqing Che,Liping Wang,Lu Zhao
Objective: The overall purpose of this study was to investigate the mechanism of macrophage polarization on chondrocyte injury in osteoarthritis and the protective effect of apigenin on chondrocytes in osteoarthritis. Method: Primary chondrocytes were isolated from the knee cartilage of three-day-old mice, and cells positive for Alsine blue staining and type II collagen immunocytochemical staining were identified and used in followup experiments. Transwell coculture was performed. Chondrocytes were inoculated in the inferior compartment, and macrophages were inoculated in the upper compartment. The experimental groups were the N group, LPS group, and LPS+ apigenin group. The effect of macrophage polarization on chondrocyte inflammation and the protective effect of apigenin on chondrocytes were verified by the drug administration. Real-time quantitative PCR (qPCR) and Western blot were used to detect the expression of RNA and protein. Experimental OA was induced by modified Hulth surgery in mice. Modified Hulth surgery was performed on the mouse’s right knee to induce experimental osteoarthritis in mice, with the nonoperative right knee serving as an ipsilateral control. The mice were randomly assigned to three groups (six mice per group): the sham group, the modified Hulth group, and the modified Hulth + apigenin group. Animals were given gavage for four weeks. The protective effect of apigenin on articular cartilage was verified by histological staining and immunohistochemical analysis. Results: Histological staining showed that apigenin had a protective effect on cartilage degeneration induced by modified Hulth surgery. The PCR results showed that apigenin significantly reduced the expression levels of IL-1, IL-6, MMP3, and MMP13 in the articular cartilage of OA mice, and it had a protective effect on articular cartilage. Apigenin reduced the levels of IL-1, IL-6, TNF-α, and IL-12 in macrophages and increased the levels of MG-L1, MG-L2, ARG-1, and IL-10, which can inhibit the M1 polarization of macrophages and promote M2 polarization. In the coculture system, apigenin decreased the protein levels of TRPM7, P-mTOR, BAX, and c-caspase3 in macrophages, while significantly increasing the protein levels of Bcl2. The levels of IL-1, IL-6, MMP13, TNF-α, P38, JNK, and ERK phosphorylation were reduced in chondrocytes. Conclusion: Apigenin alleviates cartilage injury in OA mice induced by modified Hulth. Apigenin inhibits chondrocyte inflammation through the MAPK pathway. Apigenin alleviates macrophage-polarization-induced inflammatory response and chondrocyte apoptosis in the macrophage–chondrocyte coculture system through the TRPM7-mTOR pathway.Keywords:osteoarthritis (OA);apigenin;macrophage polarization;TRPM7;MAPK
研究领域:
药理学
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免疫学
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骨科
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DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2017
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IF 1.74
Jing Wang,TongMing Li,Linquan Zang,Xuediao Pan,Sujun Wang,Yanyan Wu,Guixiang Wang
Apigenin is a nonmutagenic flavonoid that has antitumor properties. Polyamines are ubiquitous cellular polycations, which play an important role in the proliferation and differentiation of cancer cells. Highly regulated pathways control the biosynthesis and degradation of polyamines. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in the metabolism, and spermidine/spermine-N1-Acetyl transferase (SSAT) is the rate-limiting enzyme in the catabolism of polyamines. In the current study, the effect of increasing concentrations of apigenin on polyamine levels, ODC and SSAT protein expression, mRNA expression, cell proliferation and apoptosis, and the production of reactive oxygen species (ROS) was investigated in SW620 colon cancer cells. The results showed that apigenin significantly reduced cell proliferation, decreased the levels of spermidine and spermine, and increased previously downregulated putrescine contents. Apigenin also enhanced SSAT protein and mRNA levels and the production of reactive oxygen species in SW620 cells, though it had no significant effect on the levels of ODC protein or mRNA. Apigenin appears to decrease the proliferation rate of human SW620 cells by facilitating SSAT expression to induce polyamine catabolism and increasing ROS levels to induce cell apoptosis.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2017
·
IF 4.811
Ting Zhao,Yue He,Huali Chen,Yan Bai,Wenjing Hu,Liangke Zhang
We aimed to construct a novel nano-assembly carrying apigenin (APG), a hydrophobic drug, and to evaluate its in vitro targeting ability for A549 cells overexpressing CD44 receptors. The apigenin-loaded sodium hyaluronate nano-assemblies (APG/SH-NAs) were assembled by multiple non-covalent interactions between sodium hyaluronate (SH) and APG. The prepared APG/SH-NAs exhibited a small average size and narrow particle size distribution. In addition, satisfactory encapsulation efficiency and drug loading were obtained. The drug release curves indicated that APG/SH-NAs achieved a sustainable drug-release effect due to the presence of hydrophilic materials. The in vitro cytotoxicity of APG/SH-NAs against A549 cells and HepG2 cells was evaluated, and the results indicated that the prepared APG/SH-NA showed higher cytotoxicity compared to apigenin suspensions. When CD44 receptors on the surface of A549 cells were blocked by the addition of excess SH, the cytotoxicity of APG/SH-NA was significantly reduced. However, similar phenomena were not observed in HepG2 cells with relatively low CD44 receptor expression. The resulting APG/SH-NAs could efficiently facilitate the internalization of APG into A549 cells, which might be due to their high affinity for CD44 receptors. Moreover, the apoptotic rate of APG/SH-NAs through receptor-mediated endocytosis mechanism was higher than that of the other groups in A549 cells. Thus, such nano-assemblies were considered to be an effective transport system with excellent affinity for CD44 receptors to allow the SH-mediated targeted delivery of APG.
研究领域:
药剂学
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）