Anticancer and Neuroprotective Activity of Chrysin: Recent Advancement

  • Pushpendra Singh
  • Ravi S. Singh
  • Prem P. Kushwaha
  • Shashank Kumar


Chrysin is a secondary metabolite has been used as traditional herbal medicine. It has numerous biological activity including anti-viral, anti-inflammatory, anti-diabetic, anti-cancer, anti-aging, and cardioprotective etc. The basic structure of Chrysin includes C6 C3 C6 rings with diversifying substitution designs imperative for bioactivities. Chrysin plays a critical role in the modulation of multiple cell signaling pathways which are linked with inflammation, survival, growth, angiogenesis, invasion, and metastasis of cancer and neurodegenerative disease. The present book chapter highlights the molecular target, structure-activity relationship and anti-neoplastic mechanism of chrysin in cancer and neuronal therapy. Molecular docking study against chrysin with various protein showed that VEGFR2, PI3K, TAK1, and ER have good binding energy. Further, ligand-based virtual screening (LBVS) method was performed to detection of the chrysin analogous compound against ER and binding energy reviewed.


Chrysin Cancer In silico In vitro In vivo 



We would like to thank Central University of Punjab, Bathinda, Punjab, (India) and Director in-charge, National Institute of Pathology, New Delhi (India) for supporting this study with infrastructural requirements. This study was also supported by a Centenary-Post Doctoral Research Fellowship Grant-in-Aid from Indian Council of Medical Research (ICMR), Government of India awarded to PS. PPK acknowledges financial support from UGC-CSIR in the form of Senior Research Fellowship.


  1. Ahad A, Ganai AA, Mujeeb M, Siddiqui WA. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats. Toxicol Appl Pharmacol. 2014;279(1):1–7.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Ali M, Muhammad S, Shah MR, Khan A, Rashid U, Farooq U, Ullah F, Sadiq A, Ayaz M, Ali M, Ahmad M. Neurologically potent molecules from Crataegus oxyacantha; isolation, anticholinesterase inhibition, and molecular docking. Front Pharmacol. 2017;8:327.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Anandhi R, Thomas PA, Geraldine P. Evaluation of the anti-atherogenic potential of chrysin in Wistar rats. Mol Cell Biochem. 2014;385(1–2):103–13.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Arai Y, Endo S, Miyagi N, Abe N, Miura T, Nishinaka T, Terada T, Oyama M, Goda H, El-Kabbani O, Hara A. Structure–activity relationship of flavonoids as potent inhibitors of carbonyl reductase 1 (CBR1). Fitoterapia. 2015;101:51–6.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Bagheri R, Sanaat Z, Zarghami N. Synergistic effect of free and nano-encapsulated chrysin-curcumin on inhibition of hTERT gene expression in SW480 colorectal cancer cell line. Drug Res. 2018;68(06):335–43.CrossRefGoogle Scholar
  6. Balasuriya N, Rupasinghe HV. Antihypertensive properties of flavonoid-rich apple peel extract. Food Chem. 2012;135(4):2320–5.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Ballester PJ. Ultrafast shape recognition: method and applications. Future Med Chem. 2011;3(1):65–78.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Ballester PJ, Richards WG. Ultrafast shape recognition for similarity search in molecular databases. In: Proceedings of the Royal Society of London. Series A. Mathematical, physical and engineering sciences, vol. 463, 2081. London: The Royal Society; 2007. p. 1307–21.Google Scholar
  9. Ballester PJ, Westwood I, Laurieri N, Sim E, Richards WG. Prospective virtual screening with Ultrafast Shape Recognition: the identification of novel inhibitors of arylamine N-acetyltransferases. J Royal Soc Interface. 2010;7(43):335–42.CrossRefGoogle Scholar
  10. Ballester PJ, Mangold M, Howard NI, Robinson RL, Abell C, Blumberger J, Mitchell JB. Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification. J R Soc Interface. 2012;9(77):3196–207.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Balta C, Herman H, Boldura OM, Gasca I, Rosu M, Ardelean A, Hermenean A. Chrysin attenuates liver fibrosis and hepatic stellate cell activation through TGF-β/Smad signaling pathway. Chem Biol Interact. 2015;240:94–101.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Bortolotto VC, Pinheiro FC, Araujo SM, Poetini MR, Bertolazi BS, de Paula MT, Meichtry LB, de Almeida FP, de Freitas Couto S, Jesse CR, Prigol M. Chrysin reverses the depressive-like behavior induced by hypothyroidism in female mice by regulating hippocampal serotonin and dopamine. Eur J Pharmacol. 2018;822:78–84.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Campos MS, Ribeiro NC, de Lima RF, Santos MB, Vilamaior PS, Regasini LO, Biancardi MF, Taboga SR, Santos FC. Anabolic effects of chrysin on the ventral male prostate and female prostate of adult gerbils (Meriones unguiculatus). Reprod Fertil Dev. 2018;30:1180–91.PubMedCrossRefPubMedCentralGoogle Scholar
  14. Chassagne F, Haddad M, Amiel A, Phakeovilay C, Manithip C, Bourdy G, Deharo E, Marti G. A metabolomic approach to identify anti-hepatocarcinogenic compounds from plants used traditionally in the treatment of liver diseases. Fitoterapia. 2018;127:226–36.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Chen SS, Corteling R, Stevanato L, Sinden J. Polyphenols inhibit indoleamine 3, 5-dioxygenase-1 enzymatic activity—a role of immunomodulation in chemoprevention. Discov Med. 2012;14(78):327–33.PubMedPubMedCentralGoogle Scholar
  16. Ciftci O, Ozdemir I, Aydin M, Beytur A. Beneficial effects of chrysin on the reproductive system of adult male rats. Andrologia. 2012;44(3):181–6.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Czyżewska U, Siemionow K, Zaręba I, Miltyk W. Proapoptotic activity of propolis and their components on human tongue squamous cell carcinoma cell line (CAL-27). PLoS One. 2016;11(6):e0157091.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Deldar Y, Pilehvar-Soltanahmadi Y, Dadashpour M, Montazer Saheb S, Rahmati-Yamchi M, Zarghami N. An in vitro examination of the antioxidant, cytoprotective and anti-inflammatory properties of chrysin-loaded nanofibrous mats for potential wound healing applications. Artif Cells Nanomed Biotechnol. 2018;46(4):706–16.PubMedCrossRefPubMedCentralGoogle Scholar
  19. Fonseca SF, Padilha NB, Thurow S, Roehrs JA, Savegnago L, de Souza MN, Fronza MG, Collares T, Buss J, Seixas FK, Alves D. Ultrasound-promoted copper-catalyzed synthesis of bis-arylselanyl chrysin derivatives with boosted antioxidant and anticancer activities. Ultrason Sonochem. 2017;39:827–36.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Forman MS, Trojanowski JQ, Lee VM. Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med. 2004;10(10):1055.PubMedCrossRefPubMedCentralGoogle Scholar
  21. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, Repasky MP, Knoll EH, Shelley M, Perry JK, Shaw DE. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004;47(7):1739–49.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, Sanschagrin PC, Mainz DT. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein− ligand complexes. J Med Chem. 2006;49(21):6177–96.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Gao AM, Ke ZP, Shi F, Sun GC, Chen H. Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway. Chem Biol Interact. 2013;206(1):100–8.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Goes AT, Jesse CR, Antunes MS, Ladd FV, Ladd AA, Luchese C, Paroul N, Boeira SP. Protective role of chrysin on 6-hydroxydopamine-induced neurodegeneration a mouse model of Parkinson’s disease: involvement of neuroinflammation and neurotrophins. Chem Biol Interact. 2018;279:111–20.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Gresa-Arribas N, Serratosa J, Saura J, Solà C. Inhibition of CCAAT/enhancer binding protein δ expression by chrysin in microglial cells results in anti-inflammatory and neuroprotective effects. J Neurochem. 2010;115(2):526–36.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Grudzien P. Notch signaling is important in the survival, proliferation, and self-renewal of the putative breast cancer stem cell population. Chicago: Loyola University Chicago; 2010.Google Scholar
  27. Gülden M, Appel D, Syska M, Uecker S, Wages F, Seibert H. Chrysin and silibinin sensitize human glioblastoma cells for arsenic trioxide. Food Chem Toxicol. 2017;105:486–97.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Guo B, Zheng C, Cai W, Cheng J, Wang H, Li H, Sun Y, Cui W, Wang Y, Han Y, Lee SM. Multifunction of chrysin in Parkinson’s model: anti-neuronal apoptosis, neuroprotection via activation of MEF2D, and inhibition of monoamine oxidase-B. J Agric Food Chem. 2016;64(26):5324–33.PubMedCrossRefPubMedCentralGoogle Scholar
  29. He XL, Wang YH, Bi MG, Du GH. Chrysin improves cognitive deficits and brain damage induced by chronic cerebral hypoperfusion in rats. Eur J Pharmacol. 2012;680(1–3):41–8.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Hoeger B, Diether M, Ballester PJ, Köhn M. Biochemical evaluation of virtual screening methods reveals a cell-active inhibitor of the cancer-promoting phosphatases of regenerating liver. Eur J Med Chem. 2014;88:89–100.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Jia WZ, Zhao JC, Sun XL, Yao ZG, Wu HL, Xi ZQ. Additive anticancer effects of chrysin and low dose cisplatin in human malignant glioma cell (U87) proliferation and evaluation of the mechanistic pathway. J BUON. 2017;20(5):1327–36.Google Scholar
  32. Jorgensen WL, Duffy EM. Prediction of drug solubility from structure. Adv Drug Deliv Rev. 2002;54(3):355–66.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Jorgensen WL, Tirado-Rives J. The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. J Am Chem Soc. 1988;110(6):1657–66.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Jorgensen WL, Maxwell DS, Tirado-Rives J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc. 1996;118(45):11225–36.CrossRefGoogle Scholar
  35. Kang MK, Park SH, Kim YH, Lee EJ, Antika LD, Kim DY, Choi YJ, Kang YH. Dietary compound chrysin inhibits retinal neovascularization with abnormal capillaries in db/db mice. Nutrients. 2016;8(12):782.PubMedCentralCrossRefGoogle Scholar
  36. Kanwal R, Datt M, Liu X, Gupta S. Dietary flavones as dual inhibitors of DNA methyltransferases and histone methyltransferases. PLoS One. 2016;11(9):e0162956.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Kasala ER, Bodduluru LN, Madana RM, Gogoi R, Barua CC. Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives. Toxicol Lett. 2015;233(2):214–25.PubMedCrossRefPubMedCentralGoogle Scholar
  38. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J. 2013;2013:1–16.Google Scholar
  39. Laishram S, Moirangthem DS, Borah JC, Pal BC, Suman P, Gupta SK, Kalita MC, Talukdar NC. Chrysin rich Scutellaria discolor Colebr. induces cervical cancer cell death via the induction of cell cycle arrest and caspase-dependent apoptosis. Life Sci. 2015;143:105–13.PubMedCrossRefPubMedCentralGoogle Scholar
  40. León IE, Cadavid-Vargas JF, Tiscornia I, Porro V, Castelli S, Katkar P, Desideri A, Bollati-Fogolin M, Etcheverry SB. Oxidovanadium (IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model. J Biol Inorg Chem. 2015;20(7):1175–91.PubMedCrossRefPubMedCentralGoogle Scholar
  41. Li X, Wang JN, Huang JM, Xiong XK, Chen MF, Ong CN, Shen HM, Yang XF. Chrysin promotes tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induced apoptosis in human cancer cell lines. Toxicol In Vitro. 2015;25(3):630–5.CrossRefGoogle Scholar
  42. Li H, Leung KS, Wong MH, Ballester PJ. USR-VS: a web server for large-scale prospective virtual screening using ultrafast shape recognition techniques. Nucleic Acids Res. 2016;44(W1):W436–41.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Lim W, Ryu S, Bazer FW, Kim SM, Song G. Chrysin attenuates progression of ovarian cancer cells by regulating signaling cascades and mitochondrial dysfunction. J Cell Physiol. 2018;233(4):3129–40.PubMedCrossRefPubMedCentralGoogle Scholar
  44. Lin CM, Chang H, Li SY, Wu IH, Chiu JH. Chrysin inhibits lipopolysaccharide-induced angiogenesis via down-regulation of VEGF/VEGFR-2 (KDR) and IL-6/IL-6R pathways. Planta Med. 2006;72(08):708–14.PubMedCrossRefPubMedCentralGoogle Scholar
  45. Lin CM, Shyu KG, Wang BW, Chang H, Chen YH, Chiu JH. Chrysin suppresses IL-6-induced angiogenesis via down-regulation of JAK1/STAT3 and VEGF: an in vitro and in vivo approach. J Agric Food Chem. 2010;58(11):7082–7.PubMedCrossRefGoogle Scholar
  46. Lirdprapamongkol K, Sakurai H, Abdelhamed S, Yokoyama S, Maruyama T, Athikomkulchai S, Viriyaroj A, Awale S, Yagita H, Ruchirawat S, Svasti J. A flavonoid chrysin suppresses hypoxic survival and metastatic growth of mouse breast cancer cells. Oncol Rep. 2013;30(5):2357–64.PubMedCrossRefPubMedCentralGoogle Scholar
  47. Liu H, Liu K, Huang Z, Park CM, Thimmegowda NR, Jang JH, Ryoo IJ, He L, Kim SO, Oi N, Lee KW. A chrysin derivative suppresses skin cancer growth by inhibiting cyclin-dependent kinases. J Biol Chem. 2013;288:25924–37.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Lu JJ, Crimin K, Goodwin JT, Crivori P, Orrenius C, Xing L, Tandler PJ, Vidmar TJ, Amore BM, Wilson AG, Stouten PF. Influence of molecular flexibility and polar surface area metrics on oral bioavailability in the rat. J Med Chem. 2004;47(24):6104–7.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Maasomi ZJ, Soltanahmadi YP, Dadashpour M, Alipour S, Abolhasani S, Zarghami N. Synergistic anticancer effects of silibinin and chrysin in T47D breast cancer cells. Asian Pac J Cancer Prev Asian Pac J Cancer Prev. 2017;18(5):1283.Google Scholar
  50. Mani R, Natesan V. Chrysin: sources, beneficial pharmacological activities, and molecular mechanism of action. Phytochemistry. 2018;145:187–96.PubMedCrossRefPubMedCentralGoogle Scholar
  51. Mantawy EM, Esmat A, El-Bakly WM, ElDin RA, El-Demerdash E. Mechanistic clues to the protective effect of chrysin against doxorubicin-induced cardiomyopathy: plausible roles of p53, MAPK and AKT pathways. Sci Rep. 2017;7(1):1–13.CrossRefGoogle Scholar
  52. Manupati K, Dhoke NR, Debnath T, Yeeravalli R, Guguloth K, Saeidpour S, De UC, Debnath S, Das A. Inhibiting epidermal growth factor receptor signalling potentiates mesenchymal–epithelial transition of breast cancer stem cells and their responsiveness to anticancer drugs. FEBS J. 2017;284(12):1830–54.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Mattison CP, Rai R, Settlage RE, Hinchliffe DJ, Madison C, Bland JM, Brashear S, Graham CJ, Tarver MR, Florane C, Bechtel PJ. RNA-Seq analysis of developing pecan (Carya illinoinensis) embryos reveals parallel expression patterns among allergen and lipid metabolism genes. J Agric Food Chem. 2017;65(7):1443–55.PubMedCrossRefPubMedCentralGoogle Scholar
  54. Mercer LD, Kelly BL, Horne MK, Beart PM. Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures. Biochem Pharmacol. 2005;69(2):339–45.PubMedCrossRefPubMedCentralGoogle Scholar
  55. Mistry BM, Patel RV, Keum YS, Kim DH. Chrysin–benzothiazole conjugates as antioxidant and anticancer agents. Bioorg Med Chem Lett. 2015;25(23):5561–5.PubMedCrossRefPubMedCentralGoogle Scholar
  56. Mohammadi Z, Zak MS, Seidi K, Barati M, Akbarzadeh A, Zarghami N. The effect of chrysin loaded PLGA-PEG on metalloproteinase gene expression in mouse 4t1 tumor model. Drug Res. 2017;67(04):211–6.CrossRefGoogle Scholar
  57. Mohammadian F, Pilehvar-Soltanahmadi Y, Alipour S, Dadashpour M, Zarghami N. Chrysin alters microRNAs expression levels in gastric cancer cells: possible molecular mechanism. Drug Res. 2017;67(09):509–14.CrossRefGoogle Scholar
  58. Nabavi SF, Braidy N, Habtemariam S, Orhan IE, Daglia M, Manayi A, Gortzi O, Nabavi SM. Neuroprotective effects of chrysin: from chemistry to medicine. Neurochem Int. 2015;90:224–31.PubMedCrossRefPubMedCentralGoogle Scholar
  59. Owen HC, Appiah S, Hasan N, Ghali L, Elayat G, Bell C. Phytochemical modulation of apoptosis and autophagy: strategies to overcome chemoresistance in leukemic stem cells in the bone marrow microenvironment. Int Rev Neurobiol. 2017;135:249–78. AcademicPubMedCrossRefPubMedCentralGoogle Scholar
  60. Patel RV, Mistry B, Syed R, Rathi AK, Lee YJ, Sung JS, Shinf HS, Keum YS. Chrysin-piperazine conjugates as antioxidant and anticancer agents. Eur J Pharm Sci. 2016;88:166–77.PubMedCrossRefPubMedCentralGoogle Scholar
  61. Patil SP, Ballester PJ, Kerezsi CR. Prospective virtual screening for novel p53–MDM2 inhibitors using ultrafast shape recognition. J Comput Aided Mol Des. 2014;28(2):89–97.CrossRefGoogle Scholar
  62. Rajagopal C, Lankadasari MB, Aranjani JM, Harikumar KB. Targeting oncogenic transcription factors by polyphenols: a novel approach for cancer therapy. Pharmacol Res. 2018;130:273–91.PubMedCrossRefPubMedCentralGoogle Scholar
  63. Ramírez-Espinosa JJ, Saldaña-Ríos J, García-Jiménez S, Villalobos-Molina R, Ávila-Villarreal G, Rodríguez-Ocampo AN, Bernal-Fernández G, Estrada-Soto S. Chrysin induces antidiabetic, antidyslipidemic and anti-inflammatory effects in athymic nude diabetic mice. Molecules. 2017;23(1):1–8.CrossRefGoogle Scholar
  64. Rehman MU, Tahir M, Khan AQ, Khan R, Lateef A, Qamar W, Ali F, Sultana S. Chrysin suppresses renal carcinogenesis via amelioration of hyperproliferation, oxidative stress and inflammation: plausible role of NF-κB. Toxicol Lett. 2013;216(2–3):146–58.PubMedCrossRefPubMedCentralGoogle Scholar
  65. Resende FA, de Oliveira AP, de Camargo MS, Vilegas W, Varanda EA. Evaluation of estrogenic potential of flavonoids using a recombinant yeast strain and MCF7/BUS cell proliferation assay. PLoS One. 2013;8(10):e74881.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Russo P, Del Bufalo A, Cesario A. Flavonoids acting on DNA topoisomerases: recent advances and future perspectives in cancer therapy. Curr Med Chem. 2012;19(31):5287–93.PubMedCrossRefPubMedCentralGoogle Scholar
  67. Ryu S, Lim W, Bazer FW, Song G. Chrysin induces death of prostate cancer cells by inducing ROS and ER stress. J Cell Physiol. 2017;232(12):3786–97.PubMedCrossRefPubMedCentralGoogle Scholar
  68. Salimi A, Roudkenar MH, Seydi E, Sadeghi L, Mohseni A, Pirahmadi N, Pourahmad J. Chrysin as an anti-cancer agent exerts selective toxicity by directly inhibiting mitochondrial complex II and V in CLL B-lymphocytes. Cancer Investig. 2017;35(3):174–86.CrossRefGoogle Scholar
  69. Samarghandian S, Azimi-Nezhad M, Borji A, Hasanzadeh M, Jabbari F, Farkhondeh T, Samini M. Inhibitory and cytotoxic activities of chrysin on human breast adenocarcinoma cells by induction of apoptosis. Pharmacogn Mag. 2016;12(Suppl 4):S436.PubMedPubMedCentralGoogle Scholar
  70. Samarghandian S, Farkhondeh T, Azimi-Nezhad M. Protective effects of chrysin against drugs and toxic agents. Dose Response. 2017;15(2):1–10.CrossRefGoogle Scholar
  71. Sanadgol N, Shahraki Zahedani S, Sharifzadeh M, Khalseh R, Reza Barbari G, Abdollahi M. Recent updates in imperative natural compounds for healthy brain and nerve function: a systematic review of implications for multiple sclerosis. Curr Drug Targets. 2017;18(13):1499–517.PubMedCrossRefPubMedCentralGoogle Scholar
  72. Schreyer AM, Blundell T. USRCAT: real-time ultrafast shape recognition with pharmacophoric constraints. J Cheminform. 2012;4(1):1–12.CrossRefGoogle Scholar
  73. Shivakumar D, Williams J, Wu Y, Damm W, Shelley J, Sherman W. Prediction of absolute solvation free energies using molecular dynamics free energy perturbation and the OPLS force field. J Chem Theory Comput. 2010;6(5):1509–19.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Singh P, Bast F. In silico molecular docking study of natural compounds on wild and mutated epidermal growth factor receptor. Med Chem Res. 2014a;23(12):5074–85.CrossRefGoogle Scholar
  75. Singh P, Bast F. Multitargeted molecular docking study of plant-derived natural products on phosphoinositide-3 kinase pathway components. Med Chem Res. 2014b;23(4):1690–700.CrossRefGoogle Scholar
  76. Singh P, Bast F. High-throughput virtual screening, identification and in vitro biological evaluation of novel inhibitors of signal transducer and activator of transcription 3. Med Chem Res. 2015a;24(6):2694–708.CrossRefGoogle Scholar
  77. Singh P, Bast F. Screening of multi-targeted natural compounds for receptor tyrosine kinases inhibitors and biological evaluation on cancer cell lines, in silico and in vitro. Med Oncol. 2015b;32(9):233.PubMedCrossRefPubMedCentralGoogle Scholar
  78. Singh P, Singh RS, Rani A, Bast F. Homology modeling of chemokine CCR7, molecular docking, and in vitro studies evidenced plausible immunotherapeutic anticancer natural compounds. Med Chem Res. 2016;25(10):2410–24.CrossRefGoogle Scholar
  79. Stepanic V, Gasparovic AC, Troselj KG, Amic D, Zarkovic N. Selected attributes of polyphenols in targeting oxidative stress in cancer. Curr Top Med Chem. 2015;15(5):496–509.PubMedCrossRefPubMedCentralGoogle Scholar
  80. Sun LP, Chen AL, Hung HC, Chien YH, Huang JS, Huang CY, Chen YW, Chen CN. Chrysin: a histone deacetylase 8 inhibitor with anticancer activity and a suitable candidate for the standardization of Chinese propolis. J Agric Food Chem. 2012;60(47):11748–58.PubMedCrossRefPubMedCentralGoogle Scholar
  81. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50(6):537–46.PubMedPubMedCentralGoogle Scholar
  82. Thangarajan S, Ramachandran S, Krishnamurthy P. Chrysin exerts neuroprotective effects against 3-Nitropropionic acid induced behavioral despair—Mitochondrial dysfunction and striatal apoptosis via upregulating Bcl-2 gene and downregulating Bax—Bad genes in male wistar rats. Biomed Pharmacother. 2016;84:514–25.PubMedCrossRefPubMedCentralGoogle Scholar
  83. Vedagiri A, Thangarajan S. Mitigating effect of chrysin loaded solid lipid nanoparticles against amyloid β25–35 induced oxidative stress in rat hippocampal region: an efficient formulation approach for Alzheimer’s disease. Neuropeptides. 2016;58:111–25.PubMedCrossRefPubMedCentralGoogle Scholar
  84. Villar IC, Jimenez R, Galisteo M, Garcia-Saura MF, Zarzuelo A, Duarte J. Effects of chronic chrysin treatment in spontaneously hypertensive rats. Planta Med. 2002;68(9):847–50.PubMedCrossRefPubMedCentralGoogle Scholar
  85. Wadibhasme PG, Ghaisas MM, Thakurdesai PA. Anti-asthmatic potential of chrysin on ovalbumin-induced bronchoalveolar hyperresponsiveness in rats. Pharm Biol. 2011;49(5):508–15.PubMedCrossRefPubMedCentralGoogle Scholar
  86. Wang TY, Li Q, Bi KS. Bioactive flavonoids in medicinal plants: structure, activity and biological fate. Asian Pac J Pharmacol. 2017a;13(1):12–23.Google Scholar
  87. Wang Z, Deng X, Xiong S, Xiong R, Liu J, Zou L, Lei X, Cao X, Xie Z, Chen Y, Liu Y. Design, synthesis and biological evaluation of chrysin benzimidazole derivatives as potential anticancer agents. Nat Prod Res. 2017b;1–10.Google Scholar
  88. Woo KJ, Jeong YJ, Park JW, Kwon TK. Chrysin-induced apoptosis is mediated through caspase activation and Akt inactivation in U937 leukemia cells. Biochem Biophys Res Commun. 2004;325(4):1215–22.PubMedCrossRefGoogle Scholar
  89. Xia Y, Lian S, Khoi PN, Yoon HJ, Han JY, Chay KO, Kim KK, Jung YD. Chrysin inhibits cell invasion by inhibition of Recepteur d’origine Nantais via suppressing early growth response-1 and NF-κB transcription factor activities in gastric cancer cells. Int J Oncol. 2015a;46(4):1835–43.PubMedCrossRefPubMedCentralGoogle Scholar
  90. Xia Y, Lian S, Khoi PN, Yoon HJ, Joo YE, Chay KO, Kim KK, Do Jung Y. Chrysin inhibits tumor promoter-induced MMP-9 expression by blocking AP-1 via suppression of ERK and JNK pathways in gastric cancer cells. PLoS One. 2015b;10(4):e0124007.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Xu D, Jin J, Yu H, Zhao Z, Ma D, Zhang C, Jiang H. Chrysin inhibited tumor glycolysis and induced apoptosis in hepatocellular carcinoma by targeting hexokinase-2. J Exp Clin Cancer Res. 2017;36(1):44.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Xuan HZ, Zhang JH, Wang YH, Fu CL, Zhang W. Anti-tumor activity evaluation of novel chrysin–organotin compound in MCF-7 cells. Bioorg Med Chem Lett. 2016;26(2):570–4.PubMedCrossRefPubMedCentralGoogle Scholar
  93. Yang F, Jin H, Pi J, Jiang JH, Liu L, Bai HH, Yang PH, Cai JY. Anti-tumor activity evaluation of novel chrysin–organogermanium (IV) complex in MCF-7 cells. Bioorg Med Chem Lett. 2013;23(20):5544–51.PubMedCrossRefPubMedCentralGoogle Scholar
  94. Yang B, Huang J, Xiang T, Yin X, Luo X, Huang J, Luo F, Li H, Li H, Ren G. Chrysin inhibits metastatic potential of human triple-negative breast cancer cells by modulating matrix metalloproteinase-10, epithelial to mesenchymal transition, and PI3K/Akt signaling pathway. J Appl Toxicol. 2014;34(1):105–12.PubMedCrossRefGoogle Scholar
  95. Yao Y, Ni Y, Zhang J, Wang H, Shao S. The role of Notch signaling in gastric carcinoma: molecular pathogenesis and novel therapeutic targets. Oncotarget. 2017;8(32):53839.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Zeinali M, Rezaee SA, Hosseinzadeh H. An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances. Biomed Pharmacother. 2017;92:998–1009.PubMedCrossRefPubMedCentralGoogle Scholar
  97. Zeng W, Yan Y, Zhang F, Zhang C, Liang W. Chrysin promotes osteogenic differentiation via ERK/MAPK activation. Protein Cell. 2013;4(7):539–47.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Zhang Z, Li G, Szeto SS, Chong CM, Quan Q, Huang C, Cui W, Guo B, Wang Y, Han Y, Siu KM. Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease. Free Radic Biol Med. 2015;84:331–43.PubMedCrossRefPubMedCentralGoogle Scholar
  99. Zhang Q, Ma S, Liu B, Liu J, Zhu R, Li M. Chrysin induces cell apoptosis via activation of the p53/Bcl-2/caspase-9 pathway in hepatocellular carcinoma cells. Exp Ther Med. 2016;12(1):469–74.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Pushpendra Singh
    • 1
  • Ravi S. Singh
    • 2
  • Prem P. Kushwaha
    • 3
  • Shashank Kumar
    • 3
  1. 1.Tumor Biology LaboratoryNational Institute of PathologyNew DelhiIndia
  2. 2.Department of Biochemistry, Microbiology and ImmunologyUniversity of SaskatchewanSaskatoonCanada
  3. 3.Department of Biochemistry and Microbial SciencesCentral University of PunjabBathindaIndia

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