MOLECULES
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2023
·Vol. 28
·期 7
·2915
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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
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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
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IF 8.2
Lijuan Shi,Zhen Lin,Jiantong Hou,Wenhui Liu,Jing Xu,Yuanqiang Guo
Genistein is an isoflavone with chemopreventive and therapeutic effects on various types of cancers. Apparently, in contrast to the advantages of multi-target therapy, the poor water solubility of this molecule is a major obstacle to its clinical application. In this work, zein/chicory polysaccharide nanoparticles (G-zein-P NPs) were prepared by pH-induced antisolvent precipitation method for the encapsulation of genistein. Firstly, an acidic polysaccharide (CIP70-2) with a molecular weight of 66.7 kDa was identified from the roots of chicory ( Cichorium intybus ). This natural macromolecule was identified as a plant pectin, for which the structure included RG-I (rhamnogalacturonan I) and HG (homogalacturonan) regions. Using this polysaccharide, G-zein-P NPs were prepared, in which the water solubility of genistein was improved by encapsulation. The encapsulation efficiency and loading efficiency of genistein by composite nanoparticles reached 99.0 % and 6.96 %, respectively. In vitro tumor inhibition experiments showed that the inhibitory effect of G-zein-P NPs on HepG2 cells was twice that of unencapsulated genistein. Moreover, the significant inhibition of tumor development and metastasis by G-zein-P NPs was observed in zebrafish xenograft models. The results suggested that zein/chicory polysaccharide nanoparticles may be a promising delivery carrier for genistein application in cancer prevention and therapy.
研究领域:
药理学
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植物化学
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癌症治疗
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DOI
PubMed
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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PubMed
高影响因子
EBioMedicine
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2022
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IF 11.205
Xiaoqi Hong,Yujin Jian,Shenghao Ding,Jianpo Zhou,Xiaoli Zheng,Huimin Zhang,Butian Zhou,Canbin Zhuang,Jieqing Wan,Xiaoping Tong
Summary Background Stroke is one of the most common neurological diseases in the world and is clinically manifested by transient or permanent brain dysfunction. It has a high mortality and disability rate, which severely affects people's health and diminishes the quality of life. However, there is no efficient treatment that can be considered curative and there are other less well-known theories of pathogenesis. Therefore, it is imperative to gain a full understanding of the pathophysiology of ischemia and to seek new therapeutic strategies. Methods We first examined Kir4.1 channel and myelin based protein (MBP) expression in brain tissues from acute ischemic patients by Western blotting. We then established a transient ischemic mouse model (tMCAO) to conduct molecular, cell biological, transmission electron microscopy and pharmacokinetic studies, as well as in Kir4.1 cKO mice. Finally, neuroimaging and behavioral analyses were used to examine whether activation of Kir4.1 channel by luteolin could contribute to neuronal functional recovery in ischemic stroke. Findings In acute ischemic stroke patients, we first demonstrated that Kir4.1 ion channels were greatly impaired and a severe demyelination of axons occurred in ischemic infarction area of cerebral cortex in these patients. Further evidence showed that the deficits of Kir4.1 channels in NG2 glia led to the myelin loss of axons in a transient ischemic mouse model (tMCAO). Treating ischemic mice with a natural botanical extract, luteolin augmented Kir4.1 channel currents in NG2 glia and consequently promoted remyelination of axons, alleviated the infarction area and ultimately improved motor function in a series of behavioral tests. Interpretation Targeting Kir4.1 ion channels expressed in NG2 glial cells by luteolin treatment highlights an effective therapeutic strategy for a prompt brain functional recovery in ischemic stroke. Funding This work was supported by grants from the Ministry of Science and Technology China Brain Initiative (2022ZD0204702, to X.T.), the National Natural Science Foundation of China ( 82271466 , 82171279 , 31970904 and 31571063 ), the Program for Professor of Special Appointment (Eastern Scholar for Dr. X.T.) at Shanghai Institutions for Higher Learning ( 1510000084 ), Shanghai Pujiang Talent Award ( 15PJ1404600 ), Shanghai Municipal Science and Technology Major Project ( 2018SHZDZX05 ) and Shanghai Science and Technology Project ( 17411954000 ).
研究领域:
神经科学
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药理学
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分子生物学
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临床医学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2021
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IF 5.34
Yongmei Li,Zean Zhao,Jian Luo,Yanqing Jiang,Lu Li,Yanyu Chen,Leqi Zhang,Qinghua Huang,Ying Cao,Pingzheng Zhou,Ting Wu,Jianxin Pang
Background Hyperuricemia (HUA) is characterized by abnormal serum uric acid (UA) levels and demonstrated to be involved in renal injury leading to hyperuricemic nephropathy (HN). Apigenin (API), a flavonoid naturally present in tea, berries, fruits, and vegetables, exhibits various biological functions, such as antioxidant and anti-inflammatory activity. Purpose To investigate the effect of API treatment in HN and to reveal its underlying mechanisms. Methods The mice with HN were induced by potassium oxonate intraperitoneally and orally administered for two weeks. The effects of API on renal function, inflammation, fibrosis, and uric acid (UA) metabolism in mice with HN were evaluated. The effects of API on urate transporters were further examined in vitro . Results The mice with HN exhibited abnormal renal urate excretion and renal dysfunction accompanied by increased renal inflammation and fibrosis. In contrast, API reduced the levels of serum UA, serum creatinine (CRE), blood urea nitrogen (BUN) and renal inflammatory factors in mice with HN. Besides, API ameliorated the renal fibrosis via Wnt/β-catenin pathway suppression. Furthermore, API potently promoted urinary UA excretion and inhibited renal urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in mice with HN. In vitro , API competitively inhibited URAT1 and GLUT9 in a dose-dependent manner, with IC 50 values of 0.64 ± 0.14 μM and 2.63 ± 0.69 μM, respectively. Conclusions API could effectively attenuate HN through co-inhibiting UA reabsorption and Wnt/β-catenin pathway, and thus it might be a potential therapy to HN.
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
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2025
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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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高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2024
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IF 3.1
Wang Guanghui,Cheng Jianxiang,Yao Meizhen,Li Jing,Chen Ting,Zhang Jia,Du Wensheng,Chen Youguo
Ovarian cancer stands as the foremost cause of mortality among gynaecological diseases globally, characterized by high morbidity and mortality. Pinocembrin, a flavonoid from natural plant sources, exhibits diverse pharmacological properties. Despite its known pharmacological activities, its specific role in ovarian cancer treatment remains scarcely reported, and its precise molecular mechanism remains elusive. This study integrates network pharmacology and molecular docking techniques to explore pinocembrin’s potential mechanism in ovarian cancer treatment. The targets of pinocembrin were compiled from the several online databases. Ovarian cancer targets were identified using the GeneCards database, with common target genes determined by data aggregation. Protein–protein interactions were analysed using the STRING platform. Subsequent Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Molecular docking assessed the binding affinity between potential targets and active compounds. Finally, target validity was verified through in vitro experiments. We identified 163 potential pinocembrin targets for ovarian cancer treatment. GO and KEGG analyses revealed pinocembrin’s involvement in protein kinase activity, protein phosphorylation, protein kinase complexes and cancer pathways in ovarian cancer treatment. Molecular docking demonstrated strong binding affinity between pinocembrin and most potential target active sites. In vitro experiments suggested pinocembrin’s potential to induce apoptosis in ovarian cancer cells through the AKT1-mTOR signalling pathway. This study comprehensively elucidates pinocembrin’s potential targets and mechanisms against ovarian cancer, aiming to provide promising candidates for developing novel and effective alternative and/or complementary nutritional supplements for the clinical treatment of ovarian cancer.
研究领域:
肿瘤学
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药理学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Hupo Zhan,Ruixin Chen,Mei Zhong,Guowei Wang,Guihua Jiang,Xingbao Tao,Min Chen,Yunbin Jiang
Ethnopharmacological relevance Lamiophlomis rotata (Benth.) Kudo (LR, Lamiaceae) is a traditional Tibetan medicinal material in China. Tibetan medicine classic and research report suggested that LR could be used to cure rheumatoid arthritis (RA). However, the anti-RA active ingredients and pharmacological mechanisms of LR have not been elucidated. Aim of the study To explore the mechanisms and key active ingredients of total flavonoids from LR (TFLR) against RA. Materials and methods First, the mechanisms of TFLR against RA were investigated on collagen-induced arthritis (CIA) rat model by analyzing paw appearance, paw swelling, arthritis score, spleen index, thymus index, inflammatory cytokine (TNF-α, IL-1β, IL-6 and IL-17) levels in serum, histopathology of ankle joint and synovium from knee joint (hematoxylin-eosin, safranin O-fast green and DAB-TUNEL staining), and apoptosis-related protein (PI3K, Akt1, p-Akt, Bad, p-Bad, Bcl-xL and Bcl-2) levels in the synovium of ankle joints (Western blot). Then, the crucially active ingredients of TFLR against RA were explored by network pharmacology , ingredient analysis, in vitro metabolism and TNF-α-induced human RA synovial fibroblast MH7A proliferation assays. Network pharmacology was applied to predict the key active ingredients of TFLR against RA. The ingredient analysis and in vitro metabolism of TFLR were performed on HPLC, and MH7A proliferation assay were applied to evaluate the predicted results of network pharmacology. Results TFLR shown excellently anti-RA effect by reducing paw swelling, arthritis score, spleen index, thymus index and inflammatory cytokine (IL-1β, IL-6 and IL-17) levels, and improving the histopathological changes of ankle joint and synovium from knee joint in CIA rats. Results of Western blot indicated that TFLR reversed the changes of PI3K, p-Akt, p-Bad, Bcl-xL and Bcl-2 levels in the ankle joint synovium of CIA rats. Results of network pharmacology exhibited that luteolin was identified as the pivotal active ingredient of TFLR against RA. The ingredient analysis of TFLR indicated that the main ingredient in TFLR was luteoloside . The in vitro metabolism study of TFLR suggested that luteoloside could be converted to luteolin in artificial gastric juice and intestinal juice. Results of MH7A proliferation assay showed that there was no significant difference between TFLR and equal luteoloside on the viability of MH7A cells, indicating that luteoloside was the key active ingredient of TFLR against RA. Additionally, the luteolin (same mol as luteoloside) showed better inhibitory effect on the viability of MH7A cells than luteoloside. Conclusion TFLR showed anti-RA effect, and the mechanism was related to promoting synovial cell apoptosis mediated by PI3K/Akt/Bad pathway. Meanwhile, this work indicated that luteoloside was the key active ingredient of TFLR against RA. This work lays a foundation for providing TFLR product with clear mechanism and stable quality to treat RA.
研究领域:
药理学
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民族药理学
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网络药理学
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炎症
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风湿病学
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DOI
PubMed
高影响因子
MOLECULES
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2013
·Vol. 18
·期 9
·11496-11511
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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
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微生物学
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肿瘤学
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DOI
PubMed
高影响因子
Oncotarget
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2016
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IF 5.008
Yuan Qin,Dong Zhao,Hong-gang Zhou,Xing-hui Wang,Wei-long Zhong,Shuang Chen,Wen-guang Gu,Wei Wang,Chun-hong Zhang,Yan-rong Liu,Hui-juan Liu,Qiang Zhang,Yuan-qiang Guo,Tao Sun,Cheng Yang
Apigenin is a naturally occurring compound with anti-inflammatory, antioxidant, and anticancer properties. In this study, we investigated the effects of apigenin on migration and metastasis in experimental human hepatocellular carcinoma (HCC) cell lines in vitro and in vivo . Apigenin dose-dependently inhibited proliferation, migration, and invasion by PLC and Bel-7402 human HCC cells. It also suppressed tumor growth in PLC cell xenografts without altering body weight, thereby prolonging survival. Apigenin reduced Snai1 and NF-κB expression, reversed increases in epithelial-mesenchymal transition (EMT) marker levels, increased cellular adhesion, regulated actin polymerization and cell migration, and inhibited invasion and migration by HCC cells. Apigenin may therefore inhibit EMT by inhibiting the NF-κB/Snail pathway in human HCC.
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
Food Bioscience
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2021
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IF 4.24
Fuqiang Liang,Yumeng Shi,Weiwei Cao,Jiayi Shi
This study aimed to elucidate the inhibition mechanism of apigenin against porcine pancreatic lipase (PPL), and, moreover, to comprehensively reveal the molecular basis of its anti-obesity via network pharmacology approach. The results showed that apigenin inhibited PPL with an IC 50 value of 0.377 ± 0.041 mM. Spectroscopic techniques combined molecular docking suggested that apigenin could bind into the PPL active pocket, affecting its normal spatial conformation. Moreover, molecular dynamic (MD) simulations revealed that the open conformation of PPL tended to transit to the closed in the presence of apigenin, which might one important reason for the inhibition of PPL catalytic ability. Network pharmacology analysis revealed that a total of 49 proteins could be identified as potential targets for the anti-obesity effects of apigenin. According to the protein-protein interaction (PPI) network analysis, six hub targets were extracted including IGF1 , ESR1, MMP9 , PPARA , MAPK14 and NR3C1. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated that the 49 potential targets could be mapped to 30 pathways (p<0.05). Among them, PI3K-Akt signaling pathway and insulin resistance can be considered as two major pathways regulated by apigenin. Further docking studies indicated that apigenin can bind into the binding pocket of the six hub target proteins identified according to the PPI network. The results indicated that in addition to inhibiting PPL, apigenin could exhibit anti-obesity benefit through the molecular mechanisms uncovered by network pharmacology. This study proposes a new strategy to reveal the mechanisms of dietary polyphenols at the level of network pharmacology.
研究领域:
药理学
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分子生物学
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生物信息学
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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）