PHARMACOLOGY
·
2016
·
IF 1.533
Wang Zhe,Gong Yun,Zeng Da-li,Chen Lian-guo,Lin Gao-tong,Huang Cheng-ke,Sun Wei,Chen Meng-Chun,Hu Guo-xin,Chen Rui-jie
Background: CYP2C9 is one of the most important phase I drug-metabolizing enzymes in liver. The objective of this work was to investigate the effects of apigenin on the metabolism of losartan and human CYP2C9 and rat CYP2C11 activity in vitro. Methods: Different concentrations of apigenin were added to a 100 mmol/l Tris-HCl reaction mixture containing 2 pmol/ml recombinant human CYP2C9.1, 0.25 mg/ml human liver microsomes or 0.5 mg/ml rat liver microsomes to determine the half maximal inhibition or a half-maximal inhibitory concentration (IC50) on the metabolism of losartan. In addition, diclofenac used as CYP2C9 substrate was performed to determine the effects of apigenin on CYP2C9. Results: The results showed that apigenin has the inhibitory effect on the metabolism of losartan in vitro, the IC50 was 7.61, 4.10 and 11.07 μmol/l on recombinant CYP2C9 microsomes, human liver microsomes and rat liver microsomes, respectively. Meanwhile, apigenin's mode of action on human CYP2C9 activity was competitive for the substrate diclofenac. In contrast to its potent inhibition of CYP2C9 in humans (9.51 μmol/l), apigenin had lesser effects on CYP2C11 in rat (IC50 = 15.51 μmol/l). Conclusion: The observations imply that apigenin has the inhibitory effect on the metabolism of losartan and CYP2C9 activity in vitro. More attention should be paid as to when losartan should be administrated combined with apigenin
研究领域:
药理学
·
生物化学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2016
·
IF 2.857
Li Zeng,Guowen Zhang,Suyun Lin,Deming Gong
Inhibition of α-glucosidase activity may suppress postprandial hyperglycemia. The inhibition kinetic analysis showed that apigenin reversibly inhibited α-glucosidase activity with an IC50 value of (10.5 ± 0.05) × 10–6 mol L–1, and the inhibition was in a noncompetitive manner through a monophasic kinetic process. The fluorescence quenching and conformational changes determined by fluorescence and circular dichroism were due to the formation of an α-glucosidase–apigenin complex, and the binding was mainly driven by hydrophobic interactions and hydrogen bonding. The molecular simulation showed that apigenin bound to a site close to the active site of α-glucosidase, which may induce the channel closure to prevent the access of substrate, eventually leading to the inhibition of α-glucosidase. Isobolographic analysis of the interaction between myricetin and apigenin or morin showed that both of them exhibited synergistic effects at low concentrations and tended to exhibit additive or antagonistic interaction at high concentrations.
研究领域:
酶动力学
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分子生物学
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植物化学
·
糖尿病研究
·
药物发现
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Guo Jing,Li Mengna,Qi Sihua,Li Yan
Ischemic stroke remains a leading cause of mortality and long-term disability, while current therapies inadequately address oxidative stress, mitochondrial dysfunction, and blood–brain barrier (BBB) disruption during ischemia and reperfusion. Here, we developed DPCT@LIP-AP, a reactive oxygen species (ROS) responsive liposomal formulation of apigenin incorporating cysteine-arginine-glutamate-lysine-alanine (CREKA) and a ROS-cleavable thioketal linker. DPCT@LIP-AP exhibited favorable colloidal stability, ROS-dependent drug release, enhanced binding to fibrin clots, and preferential accumulation in ischemic brain tissue. In HT22 cells subjected to oxygen-glucose deprivation and reoxygenation (OGD/R), DPCT@LIP-AP reduced intracellular ROS accumulation, preserved mitochondrial membrane potential, restored adenosine triphosphate production, and suppressed the expression of IL-1β, IL-6, and TNF-α. These effects were accompanied by increased Nrf2 and HO-1 expression. In a mouse model of middle cerebral artery occlusion and reperfusion (MCAO/R), intravenous DPCT@LIP-AP reduced infarct volume and brain edema, preserved BBB and neuronal integrity, attenuated neuronal apoptosis, maintained cerebral microvascular structures, and improved neurological and behavioral outcomes. Competitive blockade with free CREKA reduced cerebral accumulation, supporting a CREKA-dependent contribution to lesion-directed delivery. Collectively, the integration of CREKA-mediated fibrin recognition with ROS-responsive apigenin release provides a coordinated strategy for protecting the neurovascular unit after cerebral ischemia and reperfusion. These findings support the further development of DPCT@LIP-AP as a nanotherapeutic platform for ischemic stroke.
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DOI
PubMed
高影响因子
MOLECULES
·
2013
·Vol. 18
·期 9
·11496-11511
·
IF 2.428
Rui Liu,Hongchi Zhang,Maosen Yuan,Jiao Zhou,Qin Tu,Jian-Jun Liu,Jinyi Wang
Two series of apigenin [5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one] derivatives,3a–3jand4a–4j, were synthesized. The apigenin and alkyl amines moieties of these compounds were separated by C2or C3spacers, respectively. The chemical structures of the apigenin derivatives were confirmed using1H-NMR,13C-NMR, and electrospray ionization mass spectroscopy. Thein vitroantibacterial and antiproliferative activities of all synthesized compounds were determined. Among the tested compounds,4a–4jdisplayed significant antibacterial activity against the tested strains (Staphylococcus aureus,Bacillus subtilis,Escherichia coli, andPseudomonas aeruginosa). Additionally,4ishowed the best inhibitory activity with minimum inhibitory concentrations of 1.95, 3.91, 3.91, and 3.91 μg/mL againstS. aureus,B. subtilis,E. coli, andP. aeruginosa, respectively. The antiproliferative activity of the apigenin derivatives was evaluated by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. We determined that4a–4jdisplayed better growth inhibition activity against four human cancer cell lines, namely, human lung (A549), human cervical (HeLa), human hepatocellular liver (HepG2), and human breast (MCF-7) cancer cells, than the parent apigenin. Compound4jwas found to be the most active antiproliferative compound against the selected cancer cells. Structure-activity relationships were also discussed based on the obtained experimental data.Keywords:synthesis;biological evaluation;apigenin derivatives;antibacterial activity;antiproliferative activity;MTT assay
研究领域:
药理学
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化学
·
微生物学
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肿瘤学
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DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2025
·
IF 4.2
Bin Xu,Yan Zhuang,Ying Zhang,Suoning Liu,Rongjun Fan,Weiru Jiang
Epithelial barrier dysfunction, critically involved in intestinal ischemia/reperfusion (I/R) injury, is significantly regulated by Nrf2-mediated oxidative stress. Apigenin, a flavonoid commonly found in fruits and vegetables with diverse biological properties, has an unclear impact on intestinal I/R injury. We hypothesize that apigenin improves intestinal barrier dysfunction by activating Nrf2 signaling. Thirty rats were randomly divided into five groups to establish an I/R model using superior mesenteric artery occlusion. Hypoxia and re-oxygenation (H/R) model was developed utilizing Caco-2 and IEC-6 cells, which were exposed to hypoxic conditions followed by re-oxygenation. Apigenin protected against intestinal mucosal damage by suppressing inflammatory cytokines release (TNF-α, IL-1β, IL-6, MPO, p < 0.01), ameliorating oxidative stress (MDA, SOD, GSH, GSH-Px, p < 0.01), and improving barrier dysfunction (DAO and TEER, p < 0.01) both in vivo and in vitro, without causing significant changes in the corresponding normal controls ( p > 0.05). Apigenin up-regulated the protein expression of Nrf2, HO-1, and tight junction (TJ) proteins ( p < 0.01). Furthermore, the knockdown of Nrf2 significantly abrogated apigenin-enhanced the TJ expression. Apigenin pretreatment alleviates intestinal I/R-induced barrier damage through Nrf2 activation and TJ upregulation, offering new strategies for preventing or treating I/R-associated intestinal diseases.
研究领域:
药理学
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分子生物学
·
消化系统疾病
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Yuanhao Sheng,Yufu Li,Huizhong Hu,Jinhong Zhong,Xin Zhong,Feilin Wang,Haihui Pan,Yongguang Bi,Fansheng Kong
Apigenin(AP) exhibits significant biological activities and pharmacological effects, including antioxidant, hypoglycemic, lipid-lowering, and anti-inflammatory properties. However, its application is limited by its low solubility, poor bioavailability, and instability. Gelatin is commonly used as a drug delivery carrier. In this study, apigenin-gelatin nanoparticles(AP-GNPs) were prepared using a pH-driven method to better explore the practical applications of AP. Characterization of AP-GNPs using FT-IR, XRD, SEM and TEM revealed that apigenin was bound to gelatin via hydrogen bonding and encapsulated within, forming a spherical amorphous structure.The particle size, PDI, zeta potential, encapsulation efficiency, and loading content of AP-GNPs were 365.3 ± 7.7 nm, 0.209 ± 0.022, −11.53 ± 0.82 mV, 83.7 ± 2.2 %, and 9.3 ± 0.3 %, respectively. Stability tests and gastrointestinal simulation digestion experiments demonstrated that AP-GNPs exhibited superior stability, solubility, and bioaccessibility compared to AP. Additionally, AP-GNPs provided protection against AAPH-induced erythrocyte haemolysis and showed inhibitory effects on the activities of α-glucosidase and α-amylase. In summary, the significant enhancement of the solubility, stability, and bioaccessibility of AP by AP-GNPs offers novel insights for the extensive application of apigenin in the pharmaceutical and food industries.
研究领域:
药学
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食品科学
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材料科学
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产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Abudureyimu Alimujiang,Yutong Kang,Wenjing Wei,Zehua Zhang,Yipeng Bai,Yong Zhu,Shixia Huo,Dengqiu Xu,Zhijian Li
Background Psoriasis is a long-lasting inflammatory skin condition marked by unusual growth of keratinocytes and infiltration of immune cells in the dermis and epidermis. Dijincao (DJC), a key component of Qing Xue Wan (QXW), is traditionally used to treat psoriasis. Although its clinical efficacy is well-recognized, the absence of pharmacological and mechanistic studies limits the validation of DJC as an effective and scientifically substantiated treatment for psoriasis. Purpose This study aimed to investigate the anti-psoriasis activity of QXW and DJC, identify their most effective constituents, and elucidate the underlying mechanisms of action. Methods Mice with imiquimod (IMQ)-induced psoriasis were treated with QXW or DJC, and the therapeutic effects were evaluated using the Psoriasis Area and Severity Index (PASI), histological analysis, immunohistochemistry, immunofluorescence, RT-PCR, and ELISA. Additionally, UPLC-QTOF/MS technology and lipopolysaccharide (LPS)-induced human keratinocytes (HaCaT) cells were employed to identify the main active components of DJC. Mechanistic insights were gained through RNA sequencing, Western blotting, cell cycle analysis, and luciferase assays. Results Treatment with QXW and DJC resulted in a significant reduction of the PASI score, skin thickness, spleen index, and inflammatory cell infiltration. Moreover, both QXW and DJC reduced serum levels of pro-inflammatory cytokines. DJC alleviated psoriasis by inhibiting keratinocyte hyperproliferation and the inflammatory response. UPLC-QTOF/MS analysis and LPS-induced HaCaT cell studies identified Apigenin as the principal active compound of DJC. Transcriptomic analysis, along with WB, cell cycle, and luciferase assays, revealed that Apigenin mitigates keratinocyte hyperproliferation and the inflammatory response by modulating the CDK2/E2F2-mediated cell cycle and IL-17 signaling pathway. Conclusion This study represents the first comprehensive comparison of the anti-psoriatic effects of QXW, DJC, and Apigenin. The findings suggest that the therapeutic effects of QXW and DJC are primarily attributed to Apigenin, which exerts anti-proliferative properties by inhibiting the CDK2/E2F2 signaling pathway.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Jie Zhang,Rui Shen,Xu Zhang,Gen Li,Xi Wang
As a natural flavonoid, apigenin (APG) has garnered considerable attention for its broad pharmacological properties. Unfortunately, the extremely poor aqueous solubility greatly restricts its clinical efficacy. Cocrystallization has been taken as an important approach to modulate physicochemical properties of parent drug. In this paper, piperazine (PIP) has been selected to assembly with APG and APG–PIP cocrystal has been successfully fabricated and characterized by single crystal X-ray diffraction and various analytical methods. Single-crystal X-ray diffraction analysis indicates APG–PIP crystallizes in the P 2 1 / c space group of monoclinic system and comprises neutral APG and PIP with the ratio of 1:1. APG and PIP are linked via O–H···N/N–H···O hydrogen bonds with a resulting 2D fes network. The 2D networks are further extended via π···π stacking interactions to afford its 3D architecture. The APG illustrates highly enhanced solubility and dissolving rate in APG–PIP cocrystal comparing with parent APG. It is notable that APG–PIP presents different equilibrium concentrations of APG along with insoluble residue when different dosages of APG–PIP are introduced. We speculate that APG and PIP may not be released equally within APG–PIP in aqueous medium due to their neutral nature and huge difference in solubility, and the existence of PIP can facilitate the dissolving of APG. This speculation has been further confirmed by investigation of relationship between equilibrium concentrations of APG and dosage of APG–PIP as well as powder dissolution experiment. The equilibrium concentrations are 0.118, 0.382, 0.556, 0.767, and 0.904 mg/mL when 5, 10, 15, 20, and 25 mg APG–PIP was put into 5 mL H 2 O and reveals good linear relation. The “spring and parachute” phenomenon and final similar solubility with parent APG in powder dissolution profile can be ascribed to the synergetic effect of metastable supersaturation and decreased PIP concentration due to withdrawing-replenishing operation.
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Xuerong Zhao,Zhuoya Wang,Guanlin Wu,Lianhong Yin,Lina Xu,Ning Wang,Jinyong Peng
Intestinal ischemia reperfusion injury (II/R injury) is a common and intractable pathophysiological process in critical patients, for which exploring new treatments and mechanisms is of great importance to improve treatment outcomes. Apigenin-7-O-Glucoside (AGL) is a sugar derivative of apigenin natural product with various pharmacological activities to protect against intestinal diseases . In this study, we synthesized two amphiphilic molecules, namely DTPA-N10–10 and mPEG-TK-DA, which can scavenge free radicals and reactive oxygen species (ROS). They were successfully encapsulated AGL through self-assembly, resulting in the formation of multi-site ROS scavenging nanoparticles called PDN@AGL. In vitro and in vivo experiments demonstrated that PDN@AGL could protect intestinal tissues by reducing lipid peroxidation, lowering ROS levels and inhibiting ferroptosis during II/R injury. Furthermore, our study revealed, for the first time, that the regulation of the ATF3/SLC7A11 pathway by PDN@AGL may play a crucial role in mitigating II/R injury. In conclusion, our study confirmed the beneficial effects of PDN@AGL in combating II/R injury through the ATF3/SLC7A11-mediated regulation of ferroptosis and oxidative stress. These findings lay the groundwork for the potential application of PDN@AGL in the treatment of II/R injury.
研究领域:
药理学
·
纳米技术
·
胃肠病学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2024
·
IF 5.6
Ruijie Xu,Zhijie Yao,Hao Zhang,Haitao Li,Wei Chen
Loss of susceptibility to anoikis signals is a crucial step in metastasis. Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management. In this study, we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily foods. Among 19 tested dietary phytochemicals, the best results were obtained with apigenin, a natural component of celery. Phenotypically, apigenin sensitized breast cancer cells to anoikis, lowered the number of circulating tumor cells, and protected against breast cancer metastasis to lung in mice. Mechanistically, we demonstrated that the thromboxane A 2 (TXA 2 )-TXA 2 receptor (TP) axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway. Blockage of TXA 2 signaling up-regulated p53 as well as its target gene p21, caused a G1 phase arrest, and finally led to apoptosis in breast cancer cells. TXA 2 level was positively correlated with breast cancer cell anoikis rate, and apigenin significantly inhibited TXA 2 biosynthesis in vitro and in vivo. Collectively, we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer, and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.
研究领域:
肿瘤学
·
药理学
·
分子生物学
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产品关联
DOI
高影响因子
CELL BIOCHEMISTRY AND FUNCTION
·
2024
·Vol. 42
·期 8
·e70015
·
IF 2.8
Yang Yu,Tianchan Zhang,Xin Li,Tianyang Yu,Fanci Meng,Yifeng Luan,Huifang Cong,Xiuhong Wu
Perimenopausal syndrome is a significant issue that disturbs women's metabolism, mood and quality of life. Apigenin (4′,5,7-trihydroxyflavone) is a natural flavonoid that exhibits antioxidant, anti-inflammatory and anticancer effects. The present study aims to investigate the effect of apigenin on perimenopausal syndrome by combining bioinformatics analysis with in vivo experiments. The mouse model with perimenopausal syndrome was established using 4-vinylcyclohexene diepoxide (VCD) treatment. Apigenin alleviated VCD-induced disorder of estrous cycle and shrinkage of ovarian tissue. The reduction of anti-Muller hormone and the increase of follicle stimulation hormone and luteinizing hormone triggered by VCD were reversed by apigenin in a dose-dependent manner. Apigenin suppressed the VCD-induced decrease of primordial, primary, secondary and antral follicle number in ovarian tissue. Oxidative stress in ovarian tissue was activated by VCD treatment through increasing the reactive oxygen species production. High concentration of apigenin significantly reversed the alteration induced by VCD. Apigenin alleviated VCD-induced cell apoptosis through regulating Bax, Bcl-2, cleaved PARP1 and caspase-3. Furthermore, the phosphorylation of AKT and FOXO3a was inhibited by VCD and activated by apigenin in a dose-dependent manner. Collectively, apigenin effectively mitigates the ovarian dysfunction through suppressing oxidative stress and apoptosis via the AKT/FOXO3a signaling pathway. Summary Perimenopausal syndrome characterized by endocrine disorders, and hormone disorders has caused physical and mental damage to the majority of women. This study aims to explore a safe and effective method for perimenopausal syndrome treatment. Apigenin is a natural flavonoid that has protective effects on ovary, while the effect and mechanism of apigenin on perimenopausal syndrome is still unclear. This study's principal finding was that apigenin alleviated the estrous cycle disorder, follicle development inhibition and hormone level disorder in model with perimenopausal syndrome. Additionally, apigenin suppressed oxidative stress and apoptosis via activating the AKT/FOXO3a signaling pathway in the ovarian tissue of perimenopausal mice model. This work provides an effective approach for the remission and treatment of perimenopausal syndrome.
研究领域:
药理学
·
内分泌学
·
妇科学
·
生物信息学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inorganic and Organometallic Polymers and Materials
·
2024
·
IF 3.9
Pang Wanyu,Gao Yali,Chang Xile,Du Guodong,Hu Zhiyong,Hu Tuoping,Ma Xuemei
An ultra-sensitive paper-based sensor for the rapid and specific detection of apigenin in Scutellaria barbata D. Don was developed. The construction process of the proposed apigenin sensor was to grow ZIF-8 in situ with MXene as a template on carbon paper (CP) electrode. The MXene with excellent conductivity and ZIF-8 with porous structure showed synergistic effect in promoting electron transfer and increasing the number of binding sites, thus providing a highly sensitive detection for apigenin. Under optimal conditions, the sensor showed an excellent linear relationship in the range of 0.01 to 10 µM, with a detection limit of 2.6 nM. This study not only constructed a new sensing platform for sensitive detection of apigenin, but also provided a new method for the detection of apigenin in Scutellaria barbata D. Don, which was of great significance for promoting the construction of an electrochemical sensor for apigenin.
研究领域:
分析化学
·
植物化学
·
电化学传感器
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）