Frontiers in Immunology
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2026
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IF 7
Haiyu Shen,Guoguo Zhi,Zihao Li,Xueqiao Yan,Zhirui Du,Shaoyang Zhang,Ruichen Yang,Xiuying Ma,Huijuan Liu,Funeng Geng,Baojie Li
BackgroundFractures are common yet lack effective pharmacological treatments. Apigenin, a natural flavone, has anti-inflammatory and pro-osteogenic effects. Here, we examined its impact on fracture healing—a multistep process involving hematoma formation, soft callus formation (endochondral differentiation), hard callus formation (osteogenic differentiation), and bone remodeling—and investigated the underlying mechanisms.MethodsFemoral fracture and calvarial injury models were established to evaluate the effects of apigenin. Local apigenin treatment was initiated at postoperative time points to compare the impact of administration timing. Fracture healing was assessed by radiography, micro-CT, histological analysis, and immunostaining. In vitro cultures were performed to examine the effects of apigenin on mesenchymal stem cell (MSC) differentiation. Quantitative PCR, Western blotting, RNA sequencing, and flow cytometry were used to evaluate inflammatory responses and chondrogenic and osteogenic differentiation. Ikbkb knockdown and BAY 11–7082 treatment were used to examine the involvement of IKKβ/NF-κB signaling. Molecular docking and molecular dynamics simulations were performed to investigate the potential interaction between apigenin and IKKβ, which was examined by cellular thermal shift assay (CETSA).ResultsApigenin significantly improved fracture healing when treatment was initiated on postoperative day 5, whereas treatment initiated on day 1 showed no clear therapeutic effect. Apigenin reduced inflammatory responses in the fracture callus and suppressed NF-κB signaling. BAY 11–7082 produced effects similar to those of apigenin in the femoral fracture model, and combined treatment did not produce a clear additional benefit. In BMSCs, apigenin promoted chondrogenic differentiation and attenuated the suppression of chondrogenic markers under inflammatory conditions, whereas its effects on osteogenic differentiation were less consistent. Ikbkb knockdown also enhanced chondrogenic differentiation, and addition of apigenin after Ikbkb knockdown produced no further clear increase. Molecular docking, molecular dynamics simulations, and CETSA provided supportive evidence for a potential interaction between apigenin and IKKβ.ConclusionsThrough modulation of IKKβ/NF-κB signaling, apigenin acts on both inflammatory responses and MSC differentiation to enhance fracture healing. The therapeutic effect was most evident when treatment was initiated on postoperative day 5, during the transition from inflammation to cartilage formation. These findings suggest that appropriately timed apigenin treatment may represent a potential strategy for improving fracture repair.
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DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2025
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IF 4.6
Xiangrong Li,Wanqing Xu,Xianfei Liu,Zhizhi Song,Zheng Li,Zihan Jia
In this study, the interaction mechanism of papain and bromelain with apigenin and luteolin in binary and ternary systems was compared and analyzed by spectroscopic methods, molecular docking, and molecular dynamics simulation. Additionally, the effects of apigenin and/or luteolin on the conformational changes and enzymatic activity of papain and bromelain were investigated. The results show that apigenin and/or luteolin exhibit a moderate binding affinity with papain/bromelain, with the binding constants K a in the range of 10 4 –10 5 L mol −1 . The order of addition of apigenin and luteolin significantly influenced their binding affinities to the enzymes. The main non-covalent forces of the papain-luteolin (first)-apigenin ternary system are hydrogen bonds and Van der Waals forces. Hydrophobic interactions, electrostatic forces and hydrogen bonds are the main non-covalent forces of other binary and ternary systems. These systems differentially alter the microenvironment of Trp and Tyr residues, secondary and tertiary structures, and enzymatic activity. Molecular docking and dynamics simulations identified specific binding sites of apigenin and/or luteolin on papain/bromelain, corroborating experimental findings. Notably, the ternary system exhibits a stronger inhibitory effect on papain activity compared to binary systems.
研究领域:
生物化学
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Xin Jin,Qing Yang,Youwen Zhang
To develop an alternative treatment for lung cancer, a combination of two potent chemotherapeutic agents – liposomal apigenin and tyroservatide – was developed. The therapeutic potential of this combination was investigated using A549 cells. Apigenin and tocopherol derivative-containing D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) liposomes might improve the delivery of apigenin to tumor cells, both in vitro and in vivo. Importantly, compared to either agent alone, the combination of apigenin TPGS liposomes and tyroservatide exhibited superior cytotoxicity, induced stronger G2 arrest, and suppressed A549 cancer cell invasion at a lower dose. The proapoptotic synergistic effects were also observed in A549 cells using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, flow cytometry, and Western blot analysis. More importantly, in vivo results showed that the combination of apigenin TPGS liposomes and tyroservatide exhibited tumor-growth inhibitory effects in A549 cell-bearing mice. In conclusion, our study showed that this combination therapy could serve as a promising synergistic therapeutic approach to improve outcomes in patients with lung cancer.
研究领域:
肿瘤学
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药学
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分子生物学
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DOI
PubMed
高影响因子
Pharmacological Reports
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2017
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IF 2.587
Ting Wu,Haixin Li,Jiasheng Chen,Ying Cao,Weimin Fu,Pingzheng Zhou,Jianxin Pang
Background Apigenin is a flavonoid compound, widely distributed in natural plants. Various studies have suggested that apigenin has inhibitory effects towards several drug transporters, such as the organic anion transporting (OAT) polypeptides , 1B1 and 1B3 (OATP1B1 and OATP1B3). However, the mechanism by which apigenin interacts with OAT1 has not been well studied. Methods MDCK cells stably-expressing OAT1 were used to examine the inhibitory effects of apigenin on OAT1. UPLC–MS/MS was used to evaluate the in vitro and in vivo effects of apigenin on the uptake of acyclovir by OAT1. Cytotoxicity was determined by the cell viability , MTT assays . Results Apigenin effectively inhibited the activity of OAT1 in a dose-dependent manner with an IC50 value of 0.737 μM. Pre-incubation of cells with apigenin caused a time-dependent inhibition (TDI) of OAT1. Additionally, we examined the interactions between apigenin and acyclovir or adefovir . Data showed that apigenin (1 μM) significantly blocked the uptake of acyclovir by OAT1 in vitro with an inhibition rate of 55%. In vivo , apigenin could increase the concentration of acyclovir in plasma when co-administered with acyclovir. Importantly, the MTT assays showed that, at a dose of 50 μM, apigenin significantly reduced the cytotoxicity of adefovir and substantially increased cell viability from 50.6% to 112.62%. Conclusion Our results demonstrate that apigenin regulates OAT1, and can cause TDI or herb-drug interaction (HDI) when used in combination with acyclovir or adefovir. Therefore, apigenin could be used as a nephroprotective agent when used in combination with the substrates of OAT1.
研究领域:
药理学
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分子生物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2017
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IF 2.759
Yang Liu,Lei Wang,Yang Du,Zhiyuan Chen,Jia Guo,Xiaodong Weng,Xiao Wang,Min Wang,Danyang Chen,Xiuheng Liu
The aim of our study is to investigate the protective effect of apigenin and the role of the JAK2/STAT3 signaling pathway in renal ischemia/reperfusion injury (IRI) in rats. For in vivo experiments, rat kidneys were subjected to 45 min of ischemia , followed by 24 h of reperfusion. The kidneys were pretreated for 24 h with apigenin (4 mg/kg) intraperitoneally in the absence or presence of the JAK2 kinase-specific inhibitor AZD1480 (30 mg/kg). The serum creatinine and urea nitrogen levels were analyzed. Histologic examinations were evaluated. Expression of p-JAK2, p-STAT3, Bcl-2, Bax and Caspase-3 was detected by immunohistochemistry or western blot . For In vitro experiments, NRK-52E cells were exposed to I/R in the absence or presence of apigenin and JAK2 siRNA was used to explore JAK2/STAT3 activity. Cell viability , cell apoptosis and expression of p-JAK2, p-STAT3, Bcl-2, Bax and Caspase-3 were examined in NRK-52E culture after I/R. Consequently, apigenin conferred a renoprotective effect on the kidneys against IRI, as evidenced by decreased serum creatinine and urea nitrogen, mitigated renal histologic damage, improved NRK-52E cell viability and a decreased apoptotic index, including up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the pro-apoptotic proteins Bax and Caspase3. However, AZD1480 and JAK2 siRNA blocked the apigenin-mediated renoprotective effects by attenuating the JAK2/STAT3 signaling pathway as well as abolished the effect of anti-oxidative stress and anti-apoptosis of apigenin. Our study demonstrates that apigenin pretreatment can protect against renal IRI via the activation of the JAK2/STAT3 signaling pathway.
研究领域:
药理学
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肾病学
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分子生物学
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2023
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IF 4.4
Zhifeng Cai,Yi Zhang,Meiling Jin,Meiling Hao,Huijuan Yang,Yang Peng,Jingwen Lu,Yaofang Zhang,Jiaxu Dong,Jiali Ren,Ran Zhang,Ya Wang
One-pot means was performed for the rapid preparation of copper nanoclusters (Cu NCs), which were employed as a fluorescence system for the sensitive apigenin measurement in pharmaceutical samples. Herein, CuCl 2 aqueous solution was reduced to Cu NCs through ascorbic acid and the Cu NCs were protected through trypsin under 65 ℃ for 4 h. The entire preparation process was rapid, facile and environmentally friendly. The trypsin-capped Cu NCs were demonstrated through ultraviolet–visible spectroscopy, fluorescence spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and fluorescence lifetime, respectively. The Cu NCs revealed blue fluorescence with emission wavelength around 465 nm under the excitation wavelength of 380 nm. The fluorescence weakening feature of Cu NCs with apigenin was observed. On this basis, a facile and sensitive turn-off fluorescent nanoprobe for the sensing of apigenin in real samples was developed. The logarithm of relative fluorescence intensity revealed a good linear relationship with apigenin contents from 0.5 μM to 300 μM with the detection limit of 0.079 μM. The Cu NCs-based fluorescent nanosensor have been employed to measure the apigenin amounts in real samples such as medical saline, bovine and human serum. The results revealed excellent potential of this Cu NCs-based fluorescent nanoprobe for the convention computation of apigenin amounts in real samples.
研究领域:
分析化学
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生物医学工程
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Ruijie Chen,Zewei Jiang,Yingfeng Cheng,Jinyao Ye,Shize Li,Yitianhe Xu,Zhanzheng Ye,Yifan Shi,Jie Ding,Yingyi Zhao,Hailun Zheng,Fugen Wu,Guangyong Lin,Congying Xie,Qing Yao,Longfa Kou
Triple negative breast cancer (TNBC) presents a formidable challenge due to its low sensitivity to many chemotherapeutic drugs and a relatively low overall survival rate in clinical practice. Photothermal therapy has recently garnered substantial interest in cancer treatment, owing to its swift therapeutic effectiveness and minimal impact on normal cells. Metal-polyphenol nanostructures have recently garnered significant attention as photothermal transduction agents due to their facile preparation and favorable photothermal properties. In this study, we employed a coordinated approach involving Fe 3+ and apigenin, a polyphenol compound, to construct the nanostructure (nFeAPG), with the assistance of β-CD and DSPE-PEG facilitating the formation of the complex nanostructure. In vitro research demonstrated that the formed nFeAPG could induce cell death by elevating intracellular oxidative stress, inhibiting antioxidative system, and promoting apoptosis and ferroptosis, and near infrared spectrum irradiation further strengthen the therapeutic outcome. In 4T1 tumor bearing mice, nFeAPG could effectively accumulate into tumor site and exhibit commendable control over tumor growth. Futher analysis demonstrated that nFeAPG ameliorated the suppressed immune microenvironment by augmenting the response of DC cells and T cells. This study underscores that nFeAPG encompasses a multifaceted capacity to combat TNBC, holding promise as a compelling therapeutic strategy for TNBC treatment.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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癌症治疗
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Qiaoyan Wang,Jie An,Qiang Xia,Daodong Pan,Lihui Du,Jun He,Yangying Sun,Ying Wang,Jinxuan Cao,Changyu Zhou
Escherichia coli and Staphylococcus aureus are the most prevalent pathogenic bacteria, often resulting in the foodborne disease outbreaks through food spoilage and foodborne infections. To prevent and control food spoilage and foodborne infections induced by Escherichia coli and Staphylococcus aureus , the antibacterial hydrogels were fabricated using fibrinogen hydrolysate-carrageenan (AHs-C) and flavonoids (apigenin and quercetin), and the antibacterial effect of the composite hydrogels against Escherichia coli and Staphylococcus aureus was further investigated. The results of mechanical property exhibited that the composite hydrogels with 0.2 % of apigenin and quercetin (AHs-C-Ap/Que) showed the highest hardness and swelling property compared with the separate addition of apigenin or quercetin. Scanning electron microscopy and atomic force microscopy showed that the dense networks were formed in the hydrogels of AHs-C-Ap/Que., and the average roughness of AHs-C-Ap/Que. significantly increased to 30.70 nm compared with AHs-C. 1 H NMR and FTIR spectra demonstrated that apigenin and quercetin were bound to AHs-C by hydrogen bond, hydrophobic interaction and Schiff base, where the interactions between Ap/Que. and AHs-C was stronger compared with the separate addition of apigenin or quercetin. The hydrogels of AHs-C-Ap/Que. showed the highest antibacterial capacity and antibacterial adhesion against Escherichia coli and Staphylococcus aureus . The antibacterial adhesion assay showed that 99 % removal ratios for E. coli and S. aureus were observed in AHs-C-Ap/Que. hydrogels, which showed a great potential to prevent food spoilage and foodborne infections.
研究领域:
材料科学
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生物技术
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食品科学
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微生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2026
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IF 11.3
Yujuan Li,Jingyi Yang,Xiaotong Shao,Yunhe Tao,Shihui Ling,Xiaomeng Li,Qifeng Ye,Bin Guo,Hongsheng Bi
Despite advancements in treatments such as atropine, the pathological changes in high myopia still lead to vision loss, highlighting the need to identify novel therapeutic targets. Clinically, axial elongation are closely related to reduced choroidal blood flow. This study revealed that the pyroptosis-associated protein Gasdermin D (GSDMD) may play a key role in high myopia. Experiments showed that chemical inhibition of GSDMD significantly reduced axial elongation and choroidal blood flow reduction. Furthermore, by screening pharmacologically active traditional Chinese medicine compounds, we identified that Artemisia argyi (Aiye) and its active ingredient apigenin act as effective GSDMD inhibitors, capable of replicating the protective effects observed with chemical inhibition. In all, this study suggests that GSDMD is a potential target mediating axial elongation and choroidal blood flow changes in high myopia, and apigenin is a potential therapeutic strategy for intervening in high myopia.
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PubMed
高影响因子
International Journal of Nanomedicine
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2026
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IF 8.7
Yingying Zhang,Lizhen Huang,Hanghang Han,Siyu Zhou,Wuling Liang,Huiming Chen,Xueke Du
Introduction Sepsis-induced acute lung injury (ALI) is a critical illness that poses a serious threat to human health, and effective treatments remain lacking. This study aimed to develop a macrophage membrane-biomimetic nano-delivery system loaded with mesoporous polydopamine (MPDA)-encapsulated apigenin (API) and to investigate its therapeutic potential in ALI.Methods In this study, we developed a macrophage membrane-coated biomimetic nano-delivery system, designated MEM@MPDA/API nanoparticles (NPs). We first systematically characterized the physicochemical properties of MEM@MPDA/API, and then evaluated its cellular uptake, reactive oxygen species (ROS) scavenging capacity, and mitochondrial function restoration through in vitro experiments. In vivo, after constructing an ALI mouse model, we assessed its active targeting to lung tissue, anti-inflammatory efficacy, pulmonary barrier repair capacity, and tissue safety following tail vein administration.Results In vivo results demonstrated that MEM@MPDA/API NPs effectively scavenged ROS, reduced inflammatory cytokine levels, and restored mitochondrial function. In the ALI mouse model, these NPs efficiently accumulated in the injured lung regions, alleviated pulmonary histopathological damage, and repaired the alveolar epithelial barrier. Integrated single-cell transcriptomics analysis and network pharmacology studies revealed that mitophagy-related pathways were activated during the progression of ALI.Conclusion This study proposes a promising biomimetic nano-delivery strategy, providing a safe and efficient potential new approach for the application of biomimetic nanomedicine in the treatment of ALI and oxidative stress-related critical diseases.
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Zhong-Hao Ji,Hai-Xiang Guo,Bingbing Wang,Wen-Zhi Ren,Jin-Ping Hu,Chengzhen Chen,Bao Yuan
Ulcerative colitis (UC) significantly impairs quality of life and incurs substantial economic costs. Apigenin, a flavonoid abundant in fruits and vegetables, has demonstrated potential in UC management. Utilizing DSS-induced UC mouse models and LS 174 T goblet cell models, this study elucidates apigenin's protective mechanisms. Dietary supplementation with 40 mg/kg apigenin markedly alleviated UC symptoms. Antibiotic-mediated microbiota depletion confirmed that apigenin's efficacy is independent of gut microbiota. Mechanistically, apigenin enhances SERCA2 expression to maintain intracellular calcium homeostasis, thereby inhibiting excessive activation of the PERK-eIF2α-ATF4-CHOP pathway, reducing goblet cell apoptosis, and preserving mucosal barrier integrity. These findings provide a robust theoretical foundation for apigenin as a dietary supplement in the prevention and mitigation of colitis.
研究领域:
生物学
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医学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Jinpeng Lv,Duo Meng,Huansha Zhang,Wenhui Xu,Xiaohong An,Chuanwei Yin,Kun Zou,Rongyin Gao
Introduction: Apigenin, a natural flavonoid with well-established antioxidant, anticancer, and anti-inflammatory activities, has recently attracted attention for its pigmentation-promoting effects. However, the underlying molecular mechanisms driving its melanogenic activity remain incompletely understood.Method: To investigate apigenin‘s effects on melanogenesis, human epidermal melanocytes (HEMCs), zebrafish embryos, and human skin explants were treated with apigenin. Melanin content, dendrite formation, and melanosome maturation were evaluated using spectrophotometry and transmission electron microscopy. Key signaling molecules and proteins involved in melanogenesis and melanosome transport were assessed by Western blotting and immunohistochemistry. The role of the c-KIT receptor was further explored through pharmacological inhibition and genetic knockdown approaches. Functional pigmentation was evaluated by assessing UVB-induced DNA damage markers.Results: Apigenin (10 μM) significantly increased melanin production by 1.8-fold in HEMCs, enhanced dendritic morphology, and promoted stage III–IV melanosome formation. Mechanistically, apigenin induced melanogenesis independently of the MC1R/cAMP/PKA pathway by directly binding to the c-KIT receptor, activating the Raf-1/ERK/RSK cascade, and upregulating MITF. This led to elevated expression of tyrosinase, TRP-1, TRP-2, and melanosome transport proteins Rab27a and Cdc42. Inhibition or knockdown of c-KIT abrogated these effects. In vivo, apigenin restored pigmentation in PTU-induced depigmented zebrafish and increased melanin content by 1.3-fold in human skin explants. Histological analysis confirmed effective melanin transfer to keratinocytes. Additionally, apigenin-treated skin showed reduced UVB-induced DNA damage, indicating enhanced photoprotection.Discussion: These findings demonstrate that apigenin stimulates melanogenesis through a novel c-KIT-dependent signaling pathway and promotes functional pigmentation with photoprotective benefits. Given its dietary origin, favorable safety profile, and multifaceted mechanisms, apigenin holds promise as a therapeutic agent for vitiligo and a natural pigmentation enhancer for dermatological use.
研究领域:
细胞生物学
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皮肤病学
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药理学
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DOI
PubMed
高影响因子
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