生物活性

• 描述CYP2C9 ranks among the most important drug-metabolizing enzymes in humans and hydroxylates 10 to 20% of commonly prescribed drugs^[3]. Apigenin, a naturally occurring plant flavone, abundantly present in common fruits and vegetables, is a competitive CYP2C9 inhibitor with a Ki value of 2 μM^[3]. It inhibited T-24 cell proliferation in a dose-dependent manner. Apigenin-mediated subG1 phase accumulation was also associated with an increase in the phospho-p53, p53, p21, and p27 levels, and with a decrease in the Cyclin A, Cyclin B1, Cyclin E, CDK2, Cdc2, and Cdc25C levels, thereby blocking cell cycle progression. In addition, apigenin increased the Bax, Bad, and Bak levels, but reduced the Bcl-xL, Bcl-2, and Mcl-1levels, and subsequently triggered the mitochondrial apoptotic pathway. Further analysis demonstrated that apigenin increased the reactive oxygen species (ROS) levels and depleted GSH in T-24 cells at 12h^[4]. Apigenin inhibited protein kinase C (PKC) by competing with adenosine triphosphate (ATP). It also reduced the level of tetradecanoyl-phorbol-13-acetate (TPA)-stimulated phosphorylation of cellular proteins and inhibited TPA-induced c-jun and c-fos expression and exhibited the reverting effect on the transformed morphology of these cells^[5]. In ovalbumin immunized BALB/C mice, production of IL-4 was down-regulated by apigenin^[6]. In vivo studies have also shown that apigenin inhibits melanoma lung metastases by impairing interaction of tumor cells with endothelium. Oral administration of apigenin was shown to cause a significant increase in uterine weight and overall uterine concentration of estrogen receptor (ER)-α in female mice, and also suppresses prostate and breast cancer cell growth through estrogen receptor β1^[6].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HEK293 cells	-	Function assay	24 h	Agonist activity at mouse PPARgamma expressed in HEK293 cells co-expressing with Gal4 reporter vector after 24 hrs by dual-luciferase reporter assay, EC50=24.9 μM	24955889
  HEK293 FS cells	-	Function assay	-	Inhibition of NOX4 expressed in HEK293 FS cells assessed as H2O2 production by H2O2/Tyr/LPO assay, IC50=1.13 μM	20731357
  human H295R cells	-	Function assay	-	Inhibition of aromatase expressed in human H295R cells, IC50=1 μM	18778944

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• 动物研究
  剂量	Rat: 10 mg/kg - 20 mg/kg[3] (p.o.) Mice: 25 mg/kg - 200 mg/kg[4] (i.p.); 5 mg/kg - 20 mg/kg[5] (p.o.)
  给药途径	p.o., i.p.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03365648	Allergic Rhinoconjunctivitis	Not Applicable	Completed	-	Italy ... more >> Fondazione IRCCS Policlinico San Matteo Pavia, (pv), Italy, 27100 Ospedale regionale San Salvatore - ASL 1 Avezzano Sulmona L'Aquila L'Aquila, AQ, Italy, 67100 A.O.U. Consorziale "Policlinico Giovanni XXIII" Bari, BA, Italy, 70126 A.O.U. Consorziale "Policlinico-Giovanni XXIII" Bari, BA, Italy, 70126 A.O.U. Policlinico Vittorio Emanuele Catania, CT, Italy, 95123 Istituto Giannina Gaslini Genova, GE, Italy, 16132 P.O. San Giovanni di Dio - ASP di Crotone Crotone, KR, Italy, 88900 A.O.U. Policlinico "G. Martino" Messina, ME, Italy, 98124 P.O. G. Salvini di Garbagnate Milanese - ASST Rhodense Garbagnate Milanese, MI, Italy, 20042 Ospedale Civile di Legnano - ASST Ovest Milanese Legnano, MI, Italy, 20162 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano, MI, Italy, 20122 Ospedale San Carlo Borromeo - ASST Azienda Socio Sanitaria Territoriale Santi Paolo E Carlo Milano, MI, Italy, 20157 Ospedale Città di Sesto San Giovanni - ASST Nord Milano Sesto San Giovanni, MI, Italy, 20099 Ospedale di Polistena "Santa Maria degli Ungheresi" - ASP di Reggio Calabria Polistena, RC, Italy, 89024 A.O.U. Policlinico Umberto I Roma, RM, Italy, 00161 P.O. di Busto Arsizio - ASST Valle Olona Busto Arsizio, VA, Italy, 21051 Az. Osp. Univ. dell'Università degli Studi della Campania "Luigi Vanvitelli" Napoli, Italy, 80138 Collapse <<
  NCT01286324	Primary Insomnia ... more >> Chronic Insomnia Collapse <<	Phase 2	Completed	-	United States, Michigan ... more >> University of Michigan Department of Family Medicine Ann Arbor, Michigan, United States, 48105 Collapse <<
  NCT03139227	Health Status Unknown	Not Applicable	Recruiting	August 31, 2020	United States, Ohio ... more >> Ohio State University Comprehensive Cancer Center Recruiting Columbus, Ohio, United States, 43210 Contact: Sagar D. Sardesai, MBBS    614-293-0066    Sagar.Sardesai@osumc.edu    Principal Investigator: Sagar D. Sardesai, MBBS          Sub-Investigator: Andrea I. Doseff, PhD          Sub-Investigator: Maryam Lustberg, MD MPH Collapse <<

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• 参考文献

• [1] Harrison ME, Power Coombs MR, et al. Exposure of breast cancer cells to a subcytotoxic dose of apigenin causes growth inhibition, oxidative stress, and hypophosphorylation of Akt. Exp Mol Pathol. 2014 Oct;97(2):211-7.

  [2] Lv X, Qiu M, et al. Apigenin inhibits enterovirus 71 replication through suppressing viral IRES activity and modulating cellular JNK pathway. Antiviral Res. 2014 Sep;109:30-41.

  [3] Si D, Wang Y, Zhou YH, Guo Y, Wang J, Zhou H, Li ZS, Fawcett JP. Mechanism of CYP2C9 inhibition by flavones and flavonols. Drug Metab Dispos. 2009 Mar;37(3):629-34. doi: 10.1124/dmd.108.023416. Epub 2008 Dec 12. PMID: 19074529.

  [4] Shi MD, Shiao CK, Lee YC, Shih YW. Apigenin, a dietary flavonoid, inhibits proliferation of human bladder cancer T-24 cells via blocking cell cycle progression and inducing apoptosis. Cancer Cell Int. 2015 Mar 29;15:33. doi: 10.1186/s12935-015-0186-0. PMID: 25859163; PMCID: PMC4391114.

  [5] Lin JK, Chen YC, Huang YT, Lin-Shiau SY. Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin. J Cell Biochem Suppl. 1997;28-29:39-48. PMID: 9589348.

  [6] Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharm Res. 2010 Jun;27(6):962-78. doi: 10.1007/s11095-010-0089-7. Epub 2010 Mar 20. PMID: 20306120; PMCID: PMC2874462.

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