Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

Flavonolignans: One Step Further in the Broad-Spectrum Approach of Cancer

Author(s): Diana S. Antal, Florina Ardelean, Stefana Avram, Ioana Z. Pavel, Corina Danciu*, Codruta Soica and Cristina Dehelean

Volume 20, Issue 15, 2020

Page: [1817 - 1830] Pages: 14

DOI: 10.2174/1871520620666200124112649

Price: $65

Abstract

Background: The small chemical class of flavonolignans encompasses unique hybrid molecules with versatile biological activities. Their anticancer effects have received considerable attention, and a large body of supporting evidence has accumulated. Moreover, their ability to interact with proteins involved in drug resistance, and to enhance the effects of conventional chemotherapeutics in decreasing cell viability make them influential partners in addressing cancer.

Objective: The review provides an outline of the various ways in which flavonolignans advance the combat against cancer. While the main focus falls on flavonolignans from milk thistle, attention is drawn to the yet, underexplored potential of less known flavonolignan subgroups derived from isoflavonoids and aurones.

Methods: Proceeding from the presentation of natural flavonolignan subtypes and their occurrence, the present work reviews these compounds with regard to their molecular targets in cancer, anti-angiogenetic effects, synergistic efficacy in conjunction with anticancer agents, reversal of drug resistance, and importance in overcoming the side effects of anticancer therapy. Recent advances in the endeavor to improve flavonolignan bioavailability in cancer are also presented.

Conclusions: Significant progress has been achieved in detailing the molecular mechanisms of silybin and its congeners in experimental models of cancer. The availability of novel formulations with improved bioavailability, and data from phase I clinical trials in cancer patients provide an encouraging basis for more extensive trials aimed at evaluating the benefits of Silybum flavonolignans in cancer management. On the other hand, further research on the antitumor efficacy of iso-flavonolignans and other subtypes of flavonolignans should be pursued.

Keywords: Silybum flavonolignans, chemical structure, pro-apoptotic, anti-angiogenetic, iso-flavonolignans, nanoformulation.

Graphical Abstract

[1]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod., 2016, 79(3), 629-661.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055 ] [PMID: 26852623]
[2]
Block, K.I.; Gyllenhaal, C.; Lowe, L.; Amedei, A.; Amin, A.R.M.R.; Amin, A.; Aquilano, K.; Arbiser, J.; Arreola, A.; Arzumanyan, A.; Ashraf, S.S.; Azmi, A.S.; Benencia, F.; Bhakta, D.; Bilsland, A.; Bishayee, A.; Blain, S.W.; Block, P.B.; Boosani, C.S.; Carey, T.E.; Carnero, A.; Carotenuto, M.; Casey, S.C.; Chakrabarti, M.; Chaturvedi, R.; Chen, G.Z.; Chen, H.; Chen, S.; Chen, Y.C.; Choi, B.K.; Ciriolo, M.R.; Coley, H.M.; Collins, A.R.; Connell, M.; Crawford, S.; Curran, C.S.; Dabrosin, C.; Damia, G.; Dasgupta, S.; DeBerardinis, R.J.; Decker, W.K.; Dhawan, P.; Diehl, A.M.E.; Dong, J.T.; Dou, Q.P.; Drew, J.E.; Elkord, E.; El-Rayes, B.; Feitelson, M.A.; Felsher, D.W.; Ferguson, L.R.; Fimognari, C.; Firestone, G.L.; Frezza, C.; Fujii, H.; Fuster, M.M.; Generali, D.; Georgakilas, A.G.; Gieseler, F.; Gilbertson, M.; Green, M.F.; Grue, B.; Guha, G.; Halicka, D.; Helferich, W.G.; Heneberg, P.; Hentosh, P.; Hirschey, M.D.; Hofseth, L.J.; Holcombe, R.F.; Honoki, K.; Hsu, H.Y.; Huang, G.S.; Jensen, L.D.; Jiang, W.G.; Jones, L.W.; Karpowicz, P.A.; Keith, W.N.; Kerkar, S.P.; Khan, G.N.; Khatami, M.; Ko, Y.H.; Kucuk, O.; Kulathinal, R.J.; Kumar, N.B.; Kwon, B.S.; Le, A.; Lea, M.A.; Lee, H.Y.; Lichtor, T.; Lin, L.T.; Locasale, J.W.; Lokeshwar, B.L.; Longo, V.D.; Lyssiotis, C.A.; MacKenzie, K.L.; Malhotra, M.; Marino, M.; Martinez-Chantar, M.L.; Matheu, A.; Maxwell, C.; McDonnell, E.; Meeker, A.K.; Mehrmohamadi, M.; Mehta, K.; Michelotti, G.A.; Mohammad, R.M.; Mohammed, S.I.; Morre, D.J.; Muralidhar, V.; Muqbil, I.; Murphy, M.P.; Nagaraju, G.P.; Nahta, R.; Niccolai, E.; Nowsheen, S.; Panis, C.; Pantano, F.; Parslow, V.R.; Pawelec, G.; Pedersen, P.L.; Poore, B.; Poudyal, D.; Prakash, S.; Prince, M.; Raffaghello, L.; Rathmell, J.C.; Rathmell, W.K.; Ray, S.K.; Reichrath, J.; Rezazadeh, S.; Ribatti, D.; Ricciardiello, L.; Robey, R.B.; Rodier, F.; Rupasinghe, H.P.V.; Russo, G.L.; Ryan, E.P.; Samadi, A.K.; Sanchez-Garcia, I.; Sanders, A.J.; Santini, D.; Sarkar, M.; Sasada, T.; Saxena, N.K.; Shackelford, R.E.; Shantha Kumara, H.M.C.; Sharma, D.; Shin, D.M.; Sidransky, D.; Siegelin, M.D.; Signori, E.; Singh, N.; Sivanand, S.; Sliva, D.; Smythe, C.; Spagnuolo, C.; Stafforini, D.M.; Stagg, J.; Subbarayan, P.R.; Sundin, T.; Talib, W.H.; Thompson, S.K.; Tran, P.T.; Ungefroren, H.; Vander Heiden, M.G.; Venkateswaran, V.; Vinay, D.S.; Vlachostergios, P.J.; Wang, Z.; Wellen, K.E.; Whelan, R.L.; Yang, E.S.; Yang, H.; Yang, X.; Yaswen, P.; Yedjou, C.; Yin, X.; Zhu, J.; Zollo, M. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin. Cancer Biol., 2015, 35(Suppl.), S276-S304.
[http://dx.doi.org/10.1016/j.semcancer.2015.09.007 ] [PMID: 26590477]
[4]
Ramasamy, K.; Agarwal, R. Multitargeted therapy of cancer by silymarin. Cancer Lett., 2008, 269(2), 352-362.
[http://dx.doi.org/10.1016/j.canlet.2008.03.053 ] [PMID: 18472213]
[5]
Deep, G.; Agarwal, R. Antimetastatic efficacy of silibinin: Molecular mechanisms and therapeutic potential against cancer. Cancer Metastasis Rev., 2010, 29(3), 447-463.
[http://dx.doi.org/10.1007/s10555-010-9237-0 ] [PMID: 20714788]
[6]
Bosch-Barrera, J.; Menendez, J.A. Silibinin and STAT3: A natural way of targeting transcription factors for cancer therapy. Cancer Treat. Rev., 2015, 41(6), 540-546.
[http://dx.doi.org/10.1016/j.ctrv.2015.04.008 ] [PMID: 25944486]
[7]
Davis-Searles, P.R.; Nakanishi, Y.; Kim, N.C.; Graf, T.N.; Oberlies, N.H.; Wani, M.C.; Wall, M.E.; Agarwal, R.; Kroll, D.J. Milk thistle and prostate cancer: Differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. Cancer Res., 2005, 65(10), 4448-4457.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-4662 ] [PMID: 15899838]
[8]
Katiyar, S.K. Silymarin and skin cancer prevention: Anti-inflammatory, antioxidant and immunomodulatory effects. (Review). Int. J. Oncol., 2005, 26(1), 169-176.
[http://dx.doi.org/10.3892/ijo.26.1.169 ] [PMID: 15586237]
[9]
Mastron, J.K.; Siveen, K.S.; Sethi, G.; Bishayee, A. Silymarin and hepatocellular carcinoma: A systematic, comprehensive, and critical review. Anticancer Drugs, 2015, 26(5), 475-486.
[http://dx.doi.org/10.1097/CAD.0000000000000211 ] [PMID: 25603021]
[10]
Raina, K.; Kumar, S.; Dhar, D.; Agarwal, R. Silibinin and colorectal cancer chemoprevention: A comprehensive review on mechanisms and efficacy. J. Biomed. Res., 2016, 30(6), 452-465.
[PMID: 27476880]
[11]
Greenlee, H.; Abascal, K.; Yarnell, E.; Ladas, E. Clinical applications of Silybum marianum in oncology. Integr. Cancer Ther., 2007, 6(2), 158-165.
[http://dx.doi.org/10.1177/1534735407301727 ] [PMID: 17548794]
[12]
Hsu, C.Y.; Sun, P.L.; Chang, H.C.; Perng, D.S.; Chen, Y.S. Spontaneous regression of advanced hepatocellular carcinoma: A case report. Cases J., 2009, 2(1), 6251.
[http://dx.doi.org/10.4076/1757-1626-2-6251 ] [PMID: 19918565]
[13]
Bosch-Barrera, J.; Corominas-Faja, B.; Cuyàs, E.; Martin-Castillo, B.; Brunet, J.; Menendez, J.A. Silibinin administration improves hepatic failure due to extensive liver infiltration in a breast cancer patient. Anticancer Res., 2014, 34(8), 4323-4327.
[PMID: 25075066]
[14]
Cheilari, A.; Sturm, S.; Intelmann, D.; Seger, C.; Stuppner, H. Head-to-head comparison of ultra-high-performance liquid chromatography with diode array detection versus quantitative nuclear magnetic resonance for the quantitative analysis of the silymarin complex in Silybum marianum fruit extracts. J. Agric. Food Chem., 2016, 64(7), 1618-1626.
[http://dx.doi.org/10.1021/acs.jafc.5b05494 ] [PMID: 26806429]
[15]
Wang, C.; Zhang, X.; Wei, P.; Cheng, X.; Ren, J.; Yan, S.; Zhang, W.; Jin, H. Chemical constituents from Inula wissmanniana and their anti-inflammatory activities. Arch. Pharm. Res., 2013, 36(12), 1516-1524.
[http://dx.doi.org/10.1007/s12272-013-0143-1 ] [PMID: 23703255]
[16]
Boniface, P.K.; Baptista Ferreira, S.; Roland Kaiser, C. Current state of knowledge on the traditional uses, phytochemistry, and pharmacology of the genus Hymenaea. J. Ethnopharmacol., 2017, 206, 193-223.
[http://dx.doi.org/10.1016/j.jep.2017.05.024 ] [PMID: 28536059]
[17]
Bai, N.; He, K.; Roller, M.; Lai, C.S.; Bai, L.; Pan, M.H. Flavonolignans and other constituents from Lepidium meyenii with activities in anti-inflammation and human cancer cell lines. J. Agric. Food Chem., 2015, 63(9), 2458-2463.
[http://dx.doi.org/10.1021/acs.jafc.5b00219 ] [PMID: 25667964]
[18]
Makong, Y.S.; Fotso, G.W.; Mouthe, G.H.; Lenta, B.; Rennert, R.; Sewald, N.; Arnold, N.; Wansi, J.D.; Ngadjui, B.T. Bruceadysentoside A, a new pregnane glycoside and others secondary metabolites with cytotoxic activity from Brucea antidysenterica J. F. Mill. (simaroubaceae). Nat. Prod. Res., 2019, 1-7.
[http://dx.doi.org/10.1080/14786419.2019.1655024 ] [PMID: 31434501]
[19]
Lee, M.A.; Kim, W.K.; Park, H.J.; Kang, S.S.; Lee, S.K. Anti-proliferative activity of hydnocarpin, a natural lignan, is associated with the suppression of Wnt/β-catenin signaling pathway in colon cancer cells. Bioorg. Med. Chem. Lett., 2013, 23(20), 5511-5514.
[http://dx.doi.org/10.1016/j.bmcl.2013.08.065 ] [PMID: 24018191]
[20]
Chang, C.L.; Wang, G.J.; Zhang, L.J.; Tsai, W.J.; Chen, R.Y.; Wu, Y.C.; Kuo, Y.H. Cardiovascular protective flavonolignans and flavonoids from Calamus quiquesetinervius. Phytochemistry, 2010, 71(2-3), 271-279.
[http://dx.doi.org/10.1016/j.phytochem.2009.09.025 ] [PMID: 20006366]
[21]
Lee, S.S.; Baek, N.I.; Baek, Y.S.; Chung, D.K.; Song, M.C.; Bang, M.H. New flavonolignan glycosides from the aerial parts of Zizania latifolia. Molecules, 2015, 20(4), 5616-5624.
[http://dx.doi.org/10.3390/molecules20045616 ] [PMID: 25830790]
[22]
Biedermann, D.; Vavříková, E.; Cvak, L.; Křen, V. Chemistry of silybin. Nat. Prod. Rep., 2014, 31(9), 1138-1157.
[http://dx.doi.org/10.1039/C3NP70122K ] [PMID: 24977260]
[23]
Li, M.; Fan, Y.; Zhong, T.; Yi, P.; Fan, C.; Wang, A.; Liu, J.; Xu, Y. The protective effects of vernicilignan A, a new flavonolignan isolated from Toxicodendron vernicifluum on SH-SY5Y cells against oxidative stress-induced injury. Fitoterapia, 2019, 134, 81-87.
[http://dx.doi.org/10.1016/j.fitote.2019.01.011 ] [PMID: 30690126]
[24]
Pettit, G.R.; Meng, Y.; Stevenson, C.A.; Doubek, D.L.; Knight, J.C.; Cichacz, Z.; Pettit, R.K.; Chapuis, J.C.; Schmidt, J.M. Isolation and structure of palstatin from the Amazon tree Hymeneae palustris(1). J. Nat. Prod., 2003, 66(2), 259-262.
[http://dx.doi.org/10.1021/np020231e ] [PMID: 12608861]
[25]
Chambers, C.S.; Valentova, K.; Kren, V. “Non-taxifolin” derived flavonolignans: Phytochemistry and biology. Curr. Pharm. Des., 2015, 21(38), 5489-5500.
[http://dx.doi.org/10.2174/1381612821666151002112720 ] [PMID: 26429716]
[26]
Vue, B.; Chen, Q.H. The potential of flavonolignans in prostate cancer management. Curr. Med. Chem., 2016, 23(34), 3925-3950.
[http://dx.doi.org/10.2174/0929867323666160823151833 ] [PMID: 27557939]
[27]
Yang, R.; Lan, Y.; Huang, Z.; Shao, C.; Liang, H.; Chen, Z.; Li, J. A new isoflavonolignan glycoside from the roots of Sophora tonkinensis. Rec. Nat. Prod., 2012, 6(3), 212-217.
[28]
Novakovic, M.; Djordjevic, I.; Todorovic, N.; Trifunovic, S.; Andjelkovic, B.; Mandic, B.; Jadranin, M.; Vuckovic, I.; Vajs, V.; Milosavljevic, S.; Tesevic, V. New aurone epoxide and auronolignan from the heartwood of Cotinus coggygria Scop. Nat. Prod. Res., 2019, 33(19), 2837-2844.
[http://dx.doi.org/10.1080/14786419.2018.1508141 ] [PMID: 30513208]
[29]
Conserva, L.M.; Yoshida, M.; Gottlieb, O.R.; Martinez, V.J.C.; Gottlieb, H.E. Iryantherins, lignoflavonoids of novel structural types from the Myristicaceae. Phytochemistry, 1990, 29(12), 3911-3918.
[http://dx.doi.org/10.1016/0031-9422(90)85358-M]
[30]
Foo, L.Y.; Karchesy, J. Pseudotsuganol, a biphenyl-linked pinoresinol–dihydroquercetin from douglas-fir bark: Isolation of the first true flavonolignan. J. Chem. Soc. Chem. Commun., 1989, 4, 217-219.
[http://dx.doi.org/10.1039/C39890000217]
[31]
Ma, K.; Ishikawa, T.; Seki, H.; Furihata, K.; Ueki, H.; Narimatsu, S.; Higuchi, Y.; Chaichantipyuth, C. Isolation of new isoflavonolignans, butesuperins A and B, from a Thai miracle herb, Butea superba. Heterocycles, 2005, 65(4), 893-900.
[http://dx.doi.org/10.3987/COM-05-10350]
[32]
AbouZid, S.F.; Ahmed, H.S.; Moawad, A.S.; Owis, A.I.; Chen, S.N.; Nachtergael, A.; McAlpine, J.B.; Brent Friesen, J.; Pauli, G.F. Chemotaxonomic and biosynthetic relationships between flavonolignans produced by Silybum marianum populations. Fitoterapia, 2017, 119, 175-184.
[http://dx.doi.org/10.1016/j.fitote.2017.04.002 ] [PMID: 28392269]
[33]
Sun, J.; Yu, J.; Xun, H.; Yue, Y.D.; Feng, T.; Guo, X.F. Two new compounds from the leaves of Indocalamus latifolius. J. Asian Nat. Prod. Res., 2016, 18(4), 360-365.
[http://dx.doi.org/10.1080/10286020.2015.1102227 ] [PMID: 26630581]
[34]
Biedermann, D.; Moravcová, V.; Valentová, K.; Kuzma, M.; Petráskova, L.; Císařova, I.; Křen, V. Oxidation of flavonolignan silydianin to unexpected lactone-acid derivative. Phytochem. Lett., 2019, 30, 14-20.
[http://dx.doi.org/10.1016/j.phytol.2019.01.006]
[35]
Chambers, C.S.; Holečková, V.; Petrásková, L.; Biedermann, D.; Valentová, K.; Buchta, M.; Křen, V. The silymarin composition… and why does it matter??? Food Res. Int., 2017, 100(Pt 3), 339-353.
[http://dx.doi.org/10.1016/j.foodres.2017.07.017 ] [PMID: 28964357]
[36]
Marhol, P.; Bednář, P.; Kolářová, P.; Večeřa, R.; Ulrichová, J.; Tesařová, E.; Vavříková, E.; Kuzma, M.; Křen, V. Pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasma. J. Funct. Foods, 2015, 14, 570-580.
[http://dx.doi.org/10.1016/j.jff.2015.02.031]
[37]
Brantley, S.J.; Oberlies, N.H.; Kroll, D.J.; Paine, M.F. Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations. J. Pharmacol. Exp. Ther., 2010, 332(3), 1081-1087.
[http://dx.doi.org/10.1124/jpet.109.161927 ] [PMID: 19934397]
[38]
Chang, C.L.; Zhang, L.J.; Chen, R.Y.; Wu, C.C.; Huang, H.C.; Roy, M.C.; Huang, J.P.; Wu, Y.C.; Kuo, Y.H. Quiquelignan A-H, eight new lignoids from the rattan palm Calamus quiquesetinervius and their antiradical, anti-inflammatory and antiplatelet aggregation activities. Bioorg. Med. Chem., 2010, 18(2), 518-525.
[http://dx.doi.org/10.1016/j.bmc.2009.12.016 ] [PMID: 20056545]
[39]
Kim, J.A.; Lau, E.K.; Pan, L.; De Blanco, E.J. NF-kappaB inhibitors from Brucea javanica exhibiting intracellular effects on reactive oxygen species. Anticancer Res., 2010, 30(9), 3295-3300.
[PMID: 20944100]
[40]
Liang, R.L.; Shi, G.R.; Yu, S.S. Lignans from seed of Hydnocarpus anthelminthica. Zhongguo Zhongyao Zazhi, 2019, 44(7), 1397-1402.
[PMID: 31090297]
[41]
Zuo, A.X.; Sun, Y.; Qian, S.X.; Rao, G.X. Study on chemical constituents of Peanut Hull. Zhong Yao Cai, 2015, 38(2), 302-304.
[PMID: 26415405]
[42]
Lan, W.; Lu, F.; Regner, M.; Zhu, Y.; Rencoret, J.; Ralph, S.A.; Zakai, U.I.; Morreel, K.; Boerjan, W.; Ralph, J. Tricin, a flavonoid monomer in monocot lignification. Plant Physiol., 2015, 167(4), 1284-1295.
[http://dx.doi.org/10.1104/pp.114.253757 ] [PMID: 25667313]
[43]
Wenzig, E.; Kunert, O.; Ferreira, D.; Schmid, M.; Schühly, W.; Bauer, R.; Hiermann, A. Flavonolignans from Avena sativa. J. Nat. Prod., 2005, 68(2), 289-292.
[http://dx.doi.org/10.1021/np049636k ] [PMID: 15730266]
[44]
Mohanlal, S.; Parvathy, R.; Shalini, V.; Helen, A.; Jayalekshmy, A. Isolation, characterization and quantification of tricin and flavonolignans in the medicinal rice Njavara (Oryza sativa L.), as compared to staple varieties. Plant Foods Hum. Nutr., 2011, 66(1), 91-96.
[http://dx.doi.org/10.1007/s11130-011-0217-5 ] [PMID: 21373805]
[45]
Bezuidenhout, S.C.; Bezuidenhout, B.C.B.; Brandt, E.V.; Ferreira, D. Oligomeric isoflavonoids. Part 2. Structure and synthesis of xanthocercin A and B, the first isoflavono-lignoids. J. Chem. Soc., Perkin Trans. 1, 1988, 1237-1241.
[http://dx.doi.org/10.1039/p19880001237]
[46]
Li, N.; Zhang, G.; Xiong, Y.; Makhabel, B.; Li, X.; Jia, X. New isoflavonolignan with quinone reductase inducing activity from Alhagi pseudalhagi (M.B.). Fitoterapia, 2010, 81(8), 1058-1061.
[http://dx.doi.org/10.1016/j.fitote.2010.06.031 ] [PMID: 20603200]
[47]
Jang, D.S.; Park, E.J.; Hawthorne, M.E.; Vigo, J.S.; Graham, J.G.; Cabieses, F.; Santarsiero, B.D.; Mesecar, A.D.; Fong, H.H.; Mehta, R.G.; Pezzuto, J.M.; Kinghorn, A.D. Potential cancer chemopreventive constituents of the seeds of Dipteryx odorata (tonka bean). J. Nat. Prod., 2003, 66(5), 583-587.
[http://dx.doi.org/10.1021/np020522n ] [PMID: 12762787]
[48]
de Oliveira, G.P.; da Silva, T.M.G.; Camara, C.A.; Santana, A.L.B.D.; Moreira, M.S.A.; Silva, T.M.S. Isolation and structure elucidation of flavonoids from Amburana cearensis resin and identification of human DNA topoisomerase II-α inhibitors. Phytochem. Lett., 2017, 22, 61-70.
[http://dx.doi.org/10.1016/j.phytol.2017.09.006]
[49]
Liu, Z.; Zheng, X.; Wang, Y.; Tang, M.; Chen, S.; Zhang, F.; Li, L.; Zhang, C.; Sun, Y. Lignans and isoflavonoids from the stems of Pisonia umbellifera. RSC Advances, 2018, 8, 16383-16391.
[http://dx.doi.org/10.1039/C8RA02240B]
[50]
Wu, F.; Yu, M.; Chen, W.; Zhou, L.; Zhang, D.; Peng, Y.; Sheng, X.; Zou, H.; Fu, J. A new isoflavonolignan glycoside from Abrus cantoniensis. Rec. Nat. Prod., 2019, 5, 418-423.
[http://dx.doi.org/10.25135/rnp.125.19.01.1165]
[51]
Lee, K.W.; Chung, K.S.; Seo, J.H.; Yim, S.V.; Park, H.J.; Choi, J.H.; Lee, K.T. Sulfuretin from heartwood of Rhus verniciflua triggers apoptosis through activation of Fas, Caspase-8, and the mitochondrial death pathway in HL-60 human leukemia cells. J. Cell. Biochem., 2012, 113(9), 2835-2844.
[http://dx.doi.org/10.1002/jcb.24158 ] [PMID: 22492309]
[52]
Kim, K.H.; Moon, E.; Choi, S.U.; Pang, C.; Kim, S.Y.; Lee, K.R. Identification of cytotoxic and anti-inflammatory constituents from the bark of Toxicodendron vernicifluum (Stokes). F.A. Barkley. J. Ethnopharmacol., 2015, 162, 231-237.
[http://dx.doi.org/10.1016/j.jep.2014.12.071 ] [PMID: 25582488]
[53]
Hahn, G.; Lehmann, H.D.; Kürten, M.; Uebel, H.; Vogel, G. On the pharmacology and toxicology of silymarin, an antihepatotoxic active principle from Silybum marianum (L.) Gaertn. Arzneimittelforschung, 1968, 18(6), 698-704.
[PMID: 5755807]
[54]
Abenavoli, L.; Izzo, A.A.; Milić, N.; Cicala, C.; Santini, A.; Capasso, R. Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytother. Res., 2018, 32(11), 2202-2213.
[http://dx.doi.org/10.1002/ptr.6171 ] [PMID: 30080294]
[55]
Csupor, D.; Csorba, A.; Hohmann, J. Recent advances in the analysis of flavonolignans of Silybum marianum. J. Pharm. Biomed. Anal., 2016, 130, 301-317.
[http://dx.doi.org/10.1016/j.jpba.2016.05.034 ] [PMID: 27321822]
[56]
Post-White, J.; Ladas, E.J.; Kelly, K.M. Advances in the use of milk thistle (Silybum marianum). Integr. Cancer Ther., 2007, 6(2), 104-109.
[http://dx.doi.org/10.1177/1534735407301632 ] [PMID: 17548789]
[57]
Bahmani, M.; Shirzad, H.; Rafieian, S.; Rafieian-Kopaei, M. Silybum marianum: Beyond hepatoprotection. J. Evid. Based Complementary Altern. Med., 2015, 20(4), 292-301.
[http://dx.doi.org/10.1177/2156587215571116 ] [PMID: 25686616]
[58]
Hosseinabadi, T.; Lorigooini, Z.; Tabarzad, M.; Salehi, B.; Rodrigues, C.F.; Martins, N.; Sharifi-Rad, J. Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer. Phytother. Res., 2019, 33(11), 2849-2861.
[http://dx.doi.org/10.1002/ptr.6470 ] [PMID: 31407422]
[59]
Kim, S.H.; Choo, G.S.; Yoo, E.S.; Woo, J.S.; Han, S.H.; Lee, J.H.; Jung, J.Y. Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells. Oncol. Rep., 2019, 42(5), 1904-1914.
[http://dx.doi.org/10.3892/or.2019.7295 ] [PMID: 31485597]
[60]
Zappavigna, S.; Vanacore, D.; Lama, S.; Potenza, N.; Russo, A.; Ferranti, P.; Dallio, M.; Federico, A.; Loguercio, C.; Sperlongano, P.; Caraglia, M.; Stiuso, P. Silybin-induced apoptosis occurs in parallel to the increase of ceramides synthesis and miRNAs secretion in human hepatocarcinoma cells. Int. J. Mol. Sci., 2019, 20(9), E2190.
[http://dx.doi.org/10.3390/ijms20092190 ] [PMID: 31058823]
[61]
Zadeh, M.M.; Motamed, N.; Ranji, N.; Majidi, M.; Falahi, F. Silibinin-induced apoptosis and downregulation of microRNA-21 and microRNA-155 in MCF-7 human breast cancer cells. J. Breast Cancer, 2016, 19(1), 45-52.
[http://dx.doi.org/10.4048/jbc.2016.19.1.45 ] [PMID: 27066095]
[62]
Hossainzadeh, S.; Ranji, N.; Naderi Sohi, A.; Najafi, F. Silibinin encapsulation in polymersome: A promising anticancer nanoparticle for inducing apoptosis and decreasing the expression level of miR-125b/miR-182 in human breast cancer cells. J. Cell. Physiol., 2019, 234(12), 22285-22298.
[http://dx.doi.org/10.1002/jcp.28795 ] [PMID: 31073992]
[63]
Sun, T.; Cheung, K.S.C.; Liu, Z.L.; Leung, F.; Lu, W.W. Matrix metallopeptidase 9 targeted by HSA-miR-494 promotes silybin-inhibited osteosarcoma. Mol. Carcinog., 2018, 57(2), 262-271.
[http://dx.doi.org/10.1002/mc.22753 ] [PMID: 29068478]
[64]
Shi, Z.; Zhou, Q.; Gao, S.; Li, W.; Li, X.; Liu, Z.; Jin, P.; Jiang, J. Silibinin inhibits endometrial carcinoma via blocking pathways of STAT3 activation and SREBP1-mediated lipid accumulation. Life Sci., 2019, 217, 70-80.
[http://dx.doi.org/10.1016/j.lfs.2018.11.037 ] [PMID: 30452972]
[65]
Anestopoulos, I.; Sfakianos, A.P.; Franco, R.; Chlichlia, K.; Panayiotidis, M.I.; Kroll, D.J.; Pappa, A. A novel role of silibinin as a putative epigenetic modulator in human prostate carcinoma. Molecules, 2016, 22(1), 62.
[http://dx.doi.org/10.3390/molecules22010062 ] [PMID: 28042859]
[66]
Liu, X.; Wu, Q.; Li, L. Functional and therapeutic significance of EZH2 in urological cancers. Oncotarget, 2017, 8(23), 38044-38055.
[http://dx.doi.org/10.18632/oncotarget.16765 ] [PMID: 28410242]
[67]
Lahiri-Chatterjee, M.; Katiyar, S.K.; Mohan, R.R.; Agarwal, R. A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res., 1999, 59(3), 622-632.
[PMID: 9973210]
[68]
Agarwal, R.; Katiyar, S.K.; Lundgren, D.W.; Mukhtar, H. Inhibitory effect of silymarin, an anti-hepatotoxic flavonoid, on 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity and mRNA in SENCAR mice. Carcinogenesis, 1994, 15(6), 1099-1103.
[http://dx.doi.org/10.1093/carcin/15.6.1099 ] [PMID: 8020140]
[69]
Deep, G.; Oberlies, N.H.; Kroll, D.J.; Agarwal, R. Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells. Carcinogenesis, 2007, 28(7), 1533-1542.
[http://dx.doi.org/10.1093/carcin/bgm069 ] [PMID: 17389612]
[70]
Jung, H.J.; Park, J.W.; Lee, J.S.; Lee, S.R.; Jang, B.C.; Suh, S.I.; Suh, M.H.; Baek, W.K. Silibinin inhibits expression of HIF-1α through suppression of protein translation in prostate cancer cells. Biochem. Biophys. Res. Commun., 2009, 390(1), 71-76.
[http://dx.doi.org/10.1016/j.bbrc.2009.09.068 ] [PMID: 19778521]
[71]
Deep, G.; Oberlies, N.H.; Kroll, D.J.; Agarwal, R. Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells. Int. J. Cancer, 2008, 123(1), 41-50.
[http://dx.doi.org/10.1002/ijc.23485 ] [PMID: 18435416]
[72]
Ben Rahal, N.; Barba, F.J.; Barth, D.; Chevalot, I. Supercritical CO2 extraction of oil, fatty acids and flavonolignans from milk thistle seeds: Evaluation of their antioxidant and cytotoxic activities in Caco-2 cells. Food Chem. Toxicol., 2015, 83, 275-282.
[http://dx.doi.org/10.1016/j.fct.2015.07.006 ] [PMID: 26172510]
[73]
Ranganathan, K.R.; Seshadri, T.R. A new flavonolignan from Hydnocarpus wightiana. Tetrahedron Lett., 1973, 14, 3481-3482.
[http://dx.doi.org/10.1016/S0040-4039(01)86949-5]
[74]
Sharma, D.K.; Hall, I.H. Hypolipidemic, anti-inflammatory, and antineoplastic activity and cytotoxicity of flavonolignans isolated from Hydnocarpus wightiana seeds. J. Nat. Prod., 1991, 54(5), 1298-1302.
[http://dx.doi.org/10.1021/np50077a010 ] [PMID: 1800632]
[75]
Mathai, B.M.; Joseph, M.M.; Maniganda, S.; Nair, J.B.; Arya, J.S.; Karunakaran, V.; Radhakrishnan, K.V.; Maiti, K.K. Guanidinium rich dendron-appended hydnocarpin exhibits superior anti-neoplastic effects through caspase mediated apoptosis. RSC Advances, 2016, 6, 52772-52780.
[http://dx.doi.org/10.1039/C6RA08724H]
[76]
Yuan, M.; Ao, Y.; Yao, N.; Xie, J.; Zhang, D.; Zhang, J.; Zhang, X.; Ye, W. Two new flavonoids from the nuts of Areca catechu. Molecules, 2019, 24(16), E2862.
[http://dx.doi.org/10.3390/molecules24162862 ] [PMID: 31394749]
[77]
Křížová, L.; Dadáková, K.; Kašparovská, J.; Kašparovský, T. Isoflavones. Molecules, 2019, 24(6), E1076.
[http://dx.doi.org/10.3390/molecules24061076 ] [PMID: 30893792]
[78]
Carmeliet, P. Angiogenesis in health and disease. Nat. Med., 2003, 9(6), 653-660.
[http://dx.doi.org/10.1038/nm0603-653 ] [PMID: 12778163]
[79]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013 ] [PMID: 21376230]
[80]
Ribeiro, A.; Abreu, R.M.V.; Dias, M.M.; Barreiro, M.F.; Ferreira, I.C.F.R. Antiangiogenic compounds: Well-established drugs versus emerging natural molecules. Cancer Lett., 2018, 415, 86-105.
[http://dx.doi.org/10.1016/j.canlet.2017.12.006 ] [PMID: 29222042]
[81]
Avram, S.; Ghiulai, R.; Pavel, I.Z.; Mioc, M.; Babuta, R.; Voicu, M.; Coricovac, D.; Danciu, C.; Dehelean, C.; Soica, C. Phytocompounds targeting cancer angiogenesis using the chorioallantoic membrane assay. In: Natural Products and Cancer Drug Discovery; Farid A. Badria, Ed.; InTech Open. UK, 2017.
[http://dx.doi.org/10.5772/intechopen.68506]
[82]
Lu, K.; Bhat, M.; Basu, S. Plants and their active compounds: Natural molecules to target angiogenesis. Angiogenesis, 2016, 19(3), 287-295.
[http://dx.doi.org/10.1007/s10456-016-9512-y ] [PMID: 27154020]
[83]
Ali, E.H.; Sharifpanah, F.; Wartenberg, M.; Sauer, H. Silibinin from Silybum marianum stimulates embryonic stem cell vascular differentiation via the STAT3/PI3-K/AKT axis and nitric oxide. Planta Med., 2018, 84(11), 768-778.
[http://dx.doi.org/10.1055/s-0044-100043 ] [PMID: 29329462]
[84]
Westwood, I.M.; Kawamura, A.; Fullam, E.; Russell, A.J.; Davies, S.G.; Sim, E. The potential of flavonolignans in prostate cancer management. Curr. Top. Med. Chem., 2006, 6, 1641-1654.
[http://dx.doi.org/10.2174/156802606778108979 ] [PMID: 16918475]
[85]
Deep, G.; Gangar, S.C.; Rajamanickam, S.; Raina, K.; Gu, M.; Agarwal, C.; Oberlies, N.H.; Agarwal, R. Angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer: Targeting VEGF-VEGFR signaling. PLoS One, 2012, 7(4), e34630.
[http://dx.doi.org/10.1371/journal.pone.0034630 ] [PMID: 22514647]
[86]
Yang, S.H.; Lin, J.K.; Huang, C.J.; Chen, W.S.; Li, S.Y.; Chiu, J.H. Silibinin inhibits angiogenesis via Flt-1, but not KDR, receptor up-regulation. J. Surg. Res., 2005, 128(1), 140-146.
[http://dx.doi.org/10.1016/j.jss.2005.04.042 ] [PMID: 15993897]
[87]
Kim, S.; Kim, S.H.; Hur, S.M.; Lee, S.K.; Kim, W.W.; Kim, J.S.; Kim, J.H.; Choe, J.H.; Nam, S.J.; Lee, J.E.; Yang, J.H. Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells. J. Ethnopharmacol., 2009, 126(2), 252-257.
[http://dx.doi.org/10.1016/j.jep.2009.08.032 ] [PMID: 19715751]
[88]
Reuben, S.C.; Gopalan, A.; Petit, D.M.; Bishayee, A. Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer. Mol. Nutr. Food Res., 2012, 56(1), 14-29.
[http://dx.doi.org/10.1002/mnfr.201100619 ] [PMID: 22125182]
[89]
Kim, S.; Choi, J.H.; Lim, H.I.; Lee, S.K.; Kim, W.W.; Kim, J.S.; Kim, J.H.; Choe, J.H.; Yang, J.H.; Nam, S.J.; Lee, J.E. Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells. Phytomedicine, 2009, 16(6-7), 573-580.
[http://dx.doi.org/10.1016/j.phymed.2008.11.006 ] [PMID: 19181503]
[90]
Tyagi, A.; Singh, R.P.; Ramasamy, K.; Raina, K.; Redente, E.F.; Dwyer-Nield, L.D.; Radcliffe, R.A.; Malkinson, A.M.; Agarwal, R. Growth inhibition and regression of lung tumors by silibinin: Modulation of angiogenesis by macrophage-associated cytokines and nuclear factor-kappaB and signal transducers and activators of transcription 3. Cancer Prev. Res. (Phila.), 2009, 2(1), 74-83.
[http://dx.doi.org/10.1158/1940-6207.CAPR-08-0095 ] [PMID: 19139021]
[91]
El Mesallamy, H.O.; Metwally, N.S.; Soliman, M.S.; Ahmed, K.A.; Abdel Moaty, M.M. The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats. Cancer Cell Int., 2011, 11(1), 38.
[http://dx.doi.org/10.1186/1475-2867-11-38 ] [PMID: 22040519]
[92]
Pezzani, R.; Salehi, B.; Vitalini, S.; Iriti, M.; Zuñiga, F.A.; Sharifi-Rad, J.; Martorell, M.; Martins, N. Synergistic effects of plant derivatives and conventional chemotherapeutic agents: An update on the cancer perspective. Medicina (Kaunas), 2019, 55(4), 110.
[http://dx.doi.org/10.3390/medicina55040110 ] [PMID: 30999703]
[93]
Belli, V.; Sforza, V.; Cardone, C.; Martinelli, E.; Barra, G.; Matrone, N.; Napolitano, S.; Morgillo, F.; Tuccillo, C.; Federico, A.; Dallio, M.; Loguercio, C.; Gravina, A.G.; De Palma, R.; Ciardiello, F.; Troiani, T. Regorafenib in combination with silybin as a novel potential strategy for the treatment of metastatic colorectal cancer. Oncotarget, 2017, 8(40), 68305-68316.
[http://dx.doi.org/10.18632/oncotarget.20054 ] [PMID: 28978118]
[94]
Gándara, L.; Sandes, E.; Di Venosa, G.; Prack Mc Cormick, B.; Rodriguez, L.; Mamone, L.; Batlle, A.; Eiján, A.M.; Casas, A. The natural flavonoid silybin improves the response to Photodynamic Therapy of bladder cancer cells. J. Photochem. Photobiol. B, 2014, 133, 55-64.
[http://dx.doi.org/10.1016/j.jphotobiol.2014.03.006 ] [PMID: 24705371]
[95]
Zhang, Y.; Ge, Y.; Ping, X.; Yu, M.; Lou, D.; Shi, W. Synergistic apoptotic effects of silibinin in enhancing paclitaxel toxicity in human gastric cancer cell lines. Mol. Med. Rep., 2018, 18(2), 1835-1841.
[http://dx.doi.org/10.3892/mmr.2018.9129 ] [PMID: 29901126]
[96]
Mao, J.; Yang, H.; Cui, T.; Pan, P.; Kabir, N.; Chen, D.; Ma, J.; Chen, X.; Chen, Y.; Yang, Y. Combined treatment with sorafenib and silibinin synergistically targets both HCC cells and cancer stem cells by enhanced inhibition of the phosphorylation of STAT3/ERK/AKT. Eur. J. Pharmacol., 2018, 832, 39-49.
[http://dx.doi.org/10.1016/j.ejphar.2018.05.027 ] [PMID: 29782854]
[97]
Gu, H.R.; Park, S.C.; Choi, S.J.; Lee, J.C.; Kim, Y.C.; Han, C.J.; Kim, J.; Yang, K.Y.; Kim, Y.J.; Noh, G.Y.; No, S.H.; Jeong, J.H. Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells. Clin. Mol. Hepatol., 2015, 21(1), 49-59.
[http://dx.doi.org/10.3350/cmh.2015.21.1.49 ] [PMID: 25834802]
[98]
Pashaei-Asl, F.; Pashaei-Asl, R.; Khodadadi, K.; Akbarzadeh, A.; Ebrahimie, E.; Pashaiasl, M. Enhancement of anticancer activity by silibinin and paclitaxel combination on the ovarian cancer. Artif. Cells Nanomed. Biotechnol., 2018, 46(7), 1483-1487.
[http://dx.doi.org/10.1080/21691401.2017.1374281 ] [PMID: 28884602]
[99]
Prack Mc Cormick, B.; Langle, Y.; Belgorosky, D.; Vanzulli, S.; Balarino, N.; Sandes, E.; Eiján, A.M. Flavonoid silybin improves the response to radiotherapy in invasive bladder cancer. J. Cell. Biochem., 2018, 119(7), 5402-5412.
[http://dx.doi.org/10.1002/jcb.26693 ] [PMID: 29363820]
[100]
Colombo, V.; Lupi, M.; Falcetta, F.; Forestieri, D.; D’Incalci, M.; Ubezio, P. Chemotherapeutic activity of silymarin combined with doxorubicin or paclitaxel in sensitive and multidrug-resistant colon cancer cells. Cancer Chemother. Pharmacol., 2011, 67(2), 369-379.
[http://dx.doi.org/10.1007/s00280-010-1335-8 ] [PMID: 20431887]
[101]
Rastegar, H.; Ahmadi Ashtiani, H.; Anjarani, S.; Bokaee, S.; Khaki, A.; Javadi, L. The role of milk thistle extract in breast carcinoma cell line (MCF-7) apoptosis with doxorubicin. Acta Med. Iran., 2013, 51(9), 591-598.
[PMID: 24338188]
[102]
Nafees, S.; Mehdi, S.H.; Zafaryab, M.; Zeya, B.; Sarwar, T.; Rizvi, M.A. Synergistic interaction of rutin and silibinin on human colon cancer cell line. Arch. Med. Res., 2018, 49(4), 226-234.
[http://dx.doi.org/10.1016/j.arcmed.2018.09.008 ] [PMID: 30314650]
[103]
Chakrabarti, M.; Ray, S.K. Synergistic anti-tumor actions of luteolin and silibinin prevented cell migration and invasion and induced apoptosis in glioblastoma SNB19 cells and glioblastoma stem cells. Brain Res., 2015, 1629, 85-93.
[http://dx.doi.org/10.1016/j.brainres.2015.10.010 ] [PMID: 26471408]
[104]
Wu, C.P.; Ohnuma, S.; Ambudkar, S.V. Discovering natural product modulators to overcome multidrug resistance in cancer chemotherapy. Curr. Pharm. Biotechnol., 2011, 12(4), 609-620.
[http://dx.doi.org/10.2174/138920111795163887 ] [PMID: 21118092]
[105]
Wang, P.; Yang, H.L.; Yang, Y.J.; Wang, L.; Lee, S.C. Overcome cancer cell drug resistance using natural products. Evid. Based Complement. Alternat. Med., 2015, 2015, 767136.
[http://dx.doi.org/10.1155/2015/767136 ] [PMID: 26421052]
[106]
Wei, T.; Chen, C.; Liu, J.; Liu, C.; Posocco, P.; Liu, X.; Cheng, Q.; Huo, S.; Liang, Z.; Fermeglia, M.; Pricl, S.; Liang, X.J.; Rocchi, P.; Peng, L. Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance. Proc. Natl. Acad. Sci. USA, 2015, 112(10), 2978-2983.
[http://dx.doi.org/10.1073/pnas.1418494112 ] [PMID: 25713374]
[107]
Sun, Y.; Kang, C.; Zhang, A.; Liu, F.; Hu, J.; Zhong, X.; Xie, J. Co-delivery of dual-drugs with nanoparticle to overcome multidrug resistance. Eur. J. Biomed. Res., 2016, 2(2), 12-18.
[108]
Kuete, V.; Mbaveng, A.T.; Zeino, M.; Fozing, C.D.; Ngameni, B.; Kapche, G.D.; Ngadjui, B.T.; Efferth, T. Cytotoxicity of three naturally occurring flavonoid derived compounds (artocarpesin, cycloartocarpesin and isobavachalcone) towards multi-factorial drug-resistant cancer cells. Phytomedicine, 2015, 22(12), 1096-1102.
[http://dx.doi.org/10.1016/j.phymed.2015.07.006 ] [PMID: 26547532]
[109]
Sadava, D.; Kane, S.E. Silibinin reverses drug resistance in human small-cell lung carcinoma cells. Cancer Lett., 2013, 339(1), 102-106.
[http://dx.doi.org/10.1016/j.canlet.2013.07.017 ] [PMID: 23879966]
[110]
Molavi, O.; Narimani, F.; Asiaee, F.; Sharifi, S.; Tarhriz, V.; Shayanfar, A.; Hejazi, M.; Lai, R. Silibinin sensitizes chemo-resistant breast cancer cells to chemotherapy. Pharm. Biol., 2017, 55(1), 729-739.
[http://dx.doi.org/10.1080/13880209.2016.1270972 ] [PMID: 28027688]
[111]
Catanzaro, D.; Gabbia, D.; Cocetta, V.; Biagi, M.; Ragazzi, E.; Montopoli, M.; Carrara, M. Silybin counteracts doxorubicin resistance by inhibiting GLUT1 expression. Fitoterapia, 2018, 124, 42-48.
[http://dx.doi.org/10.1016/j.fitote.2017.10.007 ] [PMID: 29031537]
[112]
Hagag, A.A.; Elgamsy, M.A.; El-Asy, H.M.; Mabrouk, M.M. Protective role of silymarin on hepatic and renal toxicity induced by MTX based chemotherapy in children with acute lymphoblastic leukemia. Mediterr. J. Hematol. Infect. Dis., 2016, 8(1), e2016043.
[http://dx.doi.org/10.4084/mjhid.2016.043 ] [PMID: 27648206]
[113]
Pearce, A.; Haas, M.; Viney, R.; Pearson, S.A.; Haywood, P.; Brown, C.; Ward, R. Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study. PLoS One, 2017, 12(10), e0184360.
[http://dx.doi.org/10.1371/journal.pone.0184360 ] [PMID: 29016607]
[114]
Momeni, A.; Hajigholami, A.; Geshnizjani, S.; Kheiri, S. Effect of silymarin in the prevention of Cisplatin nephrotoxicity, a clinical trial study. J. Clin. Diagn. Res., 2015, 9(4), OC11-OC13.
[http://dx.doi.org/10.7860/JCDR/2015/12776.5789 ] [PMID: 26046020]
[115]
Altaei, T. Treatment of chemotherapy-induced oral mucositis by silymarin. J. Baghdad Coll. Dent., 2011, 23(4), 81-89.
[116]
Sasu, A.; Herman, H.; Folk, A.; Baltă, C.; Rosu, M.; Miutescu, E.; Hermenean, A.; Cotoraci, C. Protective effects of silymarin on epirubicin-induced hepatotoxicity in mice. Stud. Univ. Vasile Goldis Ser. Stiint. Vietii [Life Sciences Series],, 2016, 26(3), 305-316.
[117]
Ghaderian, M.; Reisi, N.; Moafi, A.; Farasat, S. Evaluating protective effects of silymarin on liver and cardiac side effects of chemotherapy drugs in childhood acute lymphoblastic leukemia. Iran. J. Ped. Hematol. Oncol., 2017, 7(4), 207-215.
[118]
Shahbazi, F.; Sadighi, S.; Dashti-Khavidaki, S.; Shahi, F.; Mirzania, M.; Abdollahi, A.; Ghahremani, M.H. Effect of silymarin administration on cisplatin nephrotoxicity: Report from a pilot, randomized, double-blinded, placebo-controlled clinical trial. Phytother. Res., 2015, 29(7), 1046-1053.
[http://dx.doi.org/10.1002/ptr.5345 ] [PMID: 25857366]
[119]
Li, Y.; Yang, D.; Wang, Y.; Li, Z.; Zhu, C. Co-delivery doxorubicin and silybin for anti-hepatoma via enhanced oral hepatic-targeted efficiency. Int. J. Nanomedicine, 2018, 14, 301-315.
[http://dx.doi.org/10.2147/IJN.S187888 ] [PMID: 30643408]
[120]
Sasu, A.; Herman, H.; Mariasiu, T.; Rosu, M.; Balta, C.; Anghel, N.; Miutescu, E.; Cotoraci, C.; Hermenean, A. Protective effects of silymarin on epirubicin-induced mucosal barrier injury of the gastrointestinal tract. Drug Chem. Toxicol., 2015, 38(4), 442-451.
[http://dx.doi.org/10.3109/01480545.2014.992072 ] [PMID: 25609004]
[121]
Karbasforooshan, H.; Hosseini, S.; Elyasi, S.; Fani Pakdel, A.; Karimi, G. Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial. Phytother. Res., 2019, 33(2), 379-386.
[http://dx.doi.org/10.1002/ptr.6231 ] [PMID: 30479044]
[122]
Becker-Schiebe, M.; Mengs, U.; Schaefer, M.; Bulitta, M.; Hoffmann, W. Topical use of a silymarin-based preparation to prevent radiodermatitis: Results of a prospective study in breast cancer patients. Strahlenther. Onkol., 2011, 187(8), 485-491.
[http://dx.doi.org/10.1007/s00066-011-2204-z ] [PMID: 21786113]
[123]
Tran, S.; DeGiovanni, P.J.; Piel, B.; Rai, P. Cancer nanomedicine: a review of recent success in drug delivery. Clin. Transl. Med., 2017, 6(1), 44.
[http://dx.doi.org/10.1186/s40169-017-0175-0 ] [PMID: 29230567]
[124]
Graf, T.N.; Wani, M.C.; Agarwal, R.; Kroll, D.J.; Oberlies, N.H. Gram-scale purification of flavonolignan diastereoisomers from Silybum marianum (Milk Thistle) extract in support of preclinical in vivo studies for prostate cancer chemoprevention. Planta Med., 2007, 73(14), 1495-1501.
[http://dx.doi.org/10.1055/s-2007-990239 ] [PMID: 17948171]
[125]
Javed, S.; Kohli, K.; Ali, M. Reassessing bioavailability of silymarin. Altern. Med. Rev., 2011, 16(3), 239-249.
[PMID: 21951025]
[126]
Ahmad, U.; Faiyazuddin, M.; Hussain, T.; Ahmad, S.; Alshammari, T.M.; Shakeel, F. Silymarin: An insight to its formulation and analytical prospects. Acta Physiol. Plant., 2015, 37(11), 253.
[http://dx.doi.org/10.1007/s11738-015-2008-3]
[127]
Xu, P.; Yin, Q.; Shen, J.; Chen, L.; Yu, H.; Zhang, Z.; Li, Y. Synergistic inhibition of breast cancer metastasis by silibinin-loaded lipid nanoparticles containing TPGS. Int. J. Pharm., 2013, 454(1), 21-30.
[http://dx.doi.org/10.1016/j.ijpharm.2013.06.053 ] [PMID: 23830941]
[128]
Wang, Y.; Zhang, L.; Wang, Q.; Zhang, D. Recent advances in the nanotechnology-based drug delivery of Silybin. J. Biomed. Nanotechnol., 2014, 10(4), 543-558.
[http://dx.doi.org/10.1166/jbn.2014.1798 ] [PMID: 24734507]
[129]
Singh, P.; Singh, M.; Kanoujia, J.; Arya, M.; Saraf, S.K.; Saraf, S.A. Process optimization and photostability of silymarin nanostructured lipid carriers: Effect on UV-irradiated rat skin and SK-MEL 2 cell line. Drug Deliv. Transl. Res., 2016, 6(5), 597-609.
[http://dx.doi.org/10.1007/s13346-016-0317-8 ] [PMID: 27431400]
[130]
Adhikari, M.; Kaushik, N.; Ghimire, B.; Adhikari, B.; Baboota, S.; Al-Khedhairy, A.A.; Wahab, R.; Lee, S.J.; Kaushik, N.K.; Choi, E.H. Cold atmospheric plasma and silymarin nanoemulsion synergistically inhibits human melanoma tumorigenesis via targeting HGF/c-MET downstream pathway. Cell Commun. Signal., 2019, 17(1), 52.
[http://dx.doi.org/10.1186/s12964-019-0360-4 ] [PMID: 31126298]
[131]
Ahmad, U.; Akhtar, J.; Singh, S.P.; Ahmad, F.J.; Siddiqui, S. Silymarin nanoemulsion against human hepatocellular carcinoma: Development and optimization. Artif. Cells Nanomed. Biotechnol., 2018, 46(2), 231-241.
[http://dx.doi.org/10.1080/21691401.2017.1324465 ] [PMID: 28503949]
[132]
Zheng, D.; Wang, Y.; Zhang, D.; Liu, Z.; Duan, C.; Jia, L.; Wang, F.; Liu, Y.; Liu, G.; Hao, L.; Zhang, Q. In vitro antitumor activity of silybin nanosuspension in PC-3 cells. Cancer Lett., 2011, 307(2), 158-164.
[http://dx.doi.org/10.1016/j.canlet.2011.03.028 ] [PMID: 21507570]
[133]
Ochi, M.M.; Amoabediny, G.; Rezayat, S.M.; Akbarzadeh, A.; Ebrahimi, B. In vitro co-delivery evaluation of novel pegylated nano-liposomal herbal drugs of silibinin and glycyrrhizic acid (nano-phytosome) to hepatocellular carcinoma cells. Cell J., 2016, 18(2), 135-148.
[PMID: 27540518]
[134]
Tan, J.M.; Karthivashan, G.; Arulselvan, P.; Fakurazi, S.; Hussein, M.Z. Characterization and in vitro sustained release of silibinin from pH responsive carbon nanotube-based drug delivery system. J. Nanomater., 2014, 2014 Article ID, 439873.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy