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Anti-Cancer Agents in Medicinal Chemistry

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

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Review Article

Silybum marianum: An Overview of its Phytochemistry and Pharmacological Activities with Emphasis on Potential Anticancer Properties

Author(s): Aisha Nawaz, Sumera Zaib*, Imtiaz Khan*, Abrar Ahmed, Kiran Shahzadi and Huma Riaz

Volume 23, Issue 13, 2023

Published on: 10 May, 2023

Page: [1519 - 1534] Pages: 16

DOI: 10.2174/1871520623666230412111152

Price: $65

Abstract

Silybum marianum (SM) belongs to the family Asteraceae, which holds therapeutic significance in medicinal chemistry. Phytochemistry analysis revealed an abundance of active constituents, particularly silymarin, composed of polyphenols and flavonolignans. Silymarin is majorly found in leaves, seeds, and fruits and is comprised of seven flavonolignans. Silymarin derivatives, specifically silybin, were reported for their medicinal properties. This review summarizes the studies conducted to evaluate SM’s pharmacological properties and proposed mechanisms. SM exhibited anticancer properties due to being capable of modifying the induction of apoptosis, inhibiting the STAT3 pathway, decreasing the transcription of various growth factors, impeding the growth of 4T1 cells and inducing cell cycle arrest in various types of cancers, i.e., skin cancer, liver cancer, breast cancer, ovarian cancer etc. Silymarin and its derivatives protect the liver and ameliorate various immune-mediated and autoimmune hepatic diseases. Moreover, antimicrobial, antidiabetic, cardioprotective, nephroprotective, and neuroprotective activities were also reported. Based on testified in vitro and in vivo studies, SM can serve as an alternative to cure various pathological ailments.

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[1]
Valková, V.; Ďúranová, H.; Bilčíková, J.; Habán, M. Milk thistle (Silybum marianum): a valuable medicinal plant with several therapeutic purposes. J. Microbiol. Biotechnol. Food Sci., 2020, 9(4), 836-843.
[http://dx.doi.org/10.15414/jmbfs.2020.9.4.836-843]
[2]
Mayzlish-Gati, E.; Fridlender, M.; Nallathambi, R.; Selvaraj, G.; Nadarajan, S.; Koltai, H. Review on anti-cancer activity in wild plants of the Middle East. Curr. Med. Chem., 2018, 25(36), 4656-4670.
[http://dx.doi.org/10.2174/0929867324666170705113129] [PMID: 28685674]
[3]
Javeria, M.; Hussain, K. Relationship between different agro-climatic conditions and silymarin production in wild milk thistle (Silybum marianum L. Gaert.) in Pakistan. Pak. J. Bot., 2022, 54(1), 179-185.
[http://dx.doi.org/10.30848/PJB2022-1(12)]
[4]
Sajad, M.A.; Khan, M.S.; Bahadur, S.; Naeem, A.; Ali, H.; Batool, F.; Shuaib, M.; Khan, M.A.S.; Batool, S. Evaluation of chromium phytoremediation potential of some plant species of Dir Lower, Khyber Pakhtunkhwa, Pakistan. Acta Ecol. Sin., 2020, 40(2), 158-165.
[http://dx.doi.org/10.1016/j.chnaes.2019.12.002]
[5]
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]
[6]
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]
[7]
Andrew, R.; Izzo, A.A. Principles of pharmacological research of nutraceuticals. Br. J. Pharmacol., 2017, 174(11), 1177-1194.
[http://dx.doi.org/10.1111/bph.13779] [PMID: 28500635]
[8]
Qavami, N.; Naghdi, B.H.; Labbafi, M.R.; Mehrafarin, A. A review on pharmacological, cultivation and biotechnology aspects of milk thistle (Silybum marianum (L.) Gaertn.). Faslnamah-i Giyahan-i Daruyi, 2013, 12(47), 19-37.
[9]
Bijak, M. Silybin, a major bioactive component of milk thistle (Silybum marianum L. Gaernt.) Chemistry, bioavailability, and metabolism. Molecules, 2017, 22(11), 1942.
[http://dx.doi.org/10.3390/molecules22111942] [PMID: 29125572]
[10]
Soleimani, V.; Delghandi, P.S.; Moallem, S.A.; Karimi, G. Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review. Phytother. Res., 2019, 33(6), 1627-1638.
[http://dx.doi.org/10.1002/ptr.6361] [PMID: 31069872]
[11]
Fanoudi, S.; Alavi, M.S.; Karimi, G.; Hosseinzadeh, H. Milk thistle (Silybum Marianum) as an antidote or a protective agent against natural or chemical toxicities: a review. Drug Chem. Toxicol., 2020, 43(3), 240-254.
[http://dx.doi.org/10.1080/01480545.2018.1485687] [PMID: 30033764]
[12]
Zahra, N. A short review on ethnomedicinal uses and phytochemistry of Silybum marianum. Nat. Prod. Chem. Res., 2017, 5(7), 1000292.
[http://dx.doi.org/10.4172/2329-6836.1000292]
[13]
Won, D.H.; Kim, L.H.; Jang, B.; Yang, I.H.; Kwon, H.J.; Jin, B.; Oh, S.H.; Kang, J.H.; Hong, S.D.; Shin, J.A.; Cho, S.D. In vitro and in vivo anti-cancer activity of silymarin on oral cancer. Tumour Biol., 2018, 40(5), 1010428318776170.
[http://dx.doi.org/10.1177/1010428318776170] [PMID: 29764340]
[14]
Milić, N.; Milošević, N.; Suvajdžić, L.; Žarkov, M.; Abenavoli, L. New therapeutic potentials of milk thistle (Silybum marianum). Nat. Prod. Commun., 2013, 8(12), 1934578X1300801.
[http://dx.doi.org/10.1177/1934578X1300801236] [PMID: 24555302]
[15]
Le, Q.U.; Lay, H.L.; Wu, M.C.; Joshi, R.K. Phytoconstituents and pharmacological activities of Silybum marianum (Milk Thistle): A critical review. Am. J. Essent. Oils Nat. Prod., 2018, 6(4), 41-47.
[16]
Jahanafrooz, Z.; Motamed, N.; Rinner, B.; Mokhtarzadeh, A.; Baradaran, B. Silibinin to improve cancer therapeutic, as an apoptotic inducer, autophagy modulator, cell cycle inhibitor, and microRNAs regulator. Life Sci., 2018, 213, 236-247.
[http://dx.doi.org/10.1016/j.lfs.2018.10.009] [PMID: 30308184]
[17]
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]
[18]
Sy-Cordero, A.; Graf, T.; Nakanishi, Y.; Wani, M.; Agarwal, R.; Kroll, D.; Oberlies, N. Large-scale isolation of flavonolignans from Silybum marianum extract affords new minor constituents and preliminary structure-activity relationships. Planta Med., 2010, 76(6), 644-647.
[http://dx.doi.org/10.1055/s-0029-1240624] [PMID: 19941262]
[19]
Radusheva, P.; Pashev, A.; Uzunova, G.; Nikolova, K.; Gentscheva, G.; Perifanova, M.; Marudova, M. Physicochemical characteristics of seed oil of Sambucus ebulus, Coriandrum sativum L. and Silybum marianum L. Izv. Him., 2019, 51, 144-149.
[20]
Qin, N.B.; Li, S.G.; Yang, X.Y.; Gong, C.; Zhang, X.Y.; Wang, J.; Li, D.H.; Guo, Y.Q.; Li, Z.L.; Hua, H.M. Bioactive terpenoids from Silybum marianum and their suppression on NO release in LPS-induced BV-2 cells and interaction with iNOS. Bioorg. Med. Chem. Lett., 2017, 27(10), 2161-2165.
[http://dx.doi.org/10.1016/j.bmcl.2017.03.058] [PMID: 28377060]
[21]
AbouZid, S.F.; Chen, S.N.; McAlpine, J.B.; Friesen, J.B.; Pauli, G.F. Silybum marianum pericarp yields enhanced silymarin products. Fitoterapia, 2016, 112(112), 136-143.
[http://dx.doi.org/10.1016/j.fitote.2016.05.012] [PMID: 27233988]
[22]
Fathi-Achachlouei, B.; Azadmard-Damirchi, S.; Zahedi, Y.; Shaddel, R. Microwave pretreatment as a promising strategy for increment of nutraceutical content and extraction yield of oil from milk thistle seed. Ind. Crops Prod., 2019, 128, 527-533.
[http://dx.doi.org/10.1016/j.indcrop.2018.11.034]
[23]
Mhamdi, B.; Abbassi, F.; Smaoui, A.; Abdelly, C.; Marzouk, B. Fatty acids, essential oil and phenolics composition of Silybum marianum seeds and their antioxidant activities. Pak. J. Pharm. Sci., 2016, 29(3), 953-959.
[24]
Di Costanzo, A.; Angelico, R. Formulation strategies for enhancing the bioavailability of silymarin: the state of the art. Molecules, 2019, 24(11), 2155.
[http://dx.doi.org/10.3390/molecules24112155] [PMID: 31181687]
[25]
Cavaretta, M. Therapeutic review. Milk Thistle. J. Exot. Pet Med., 2015, 24(4), 470-472.
[http://dx.doi.org/10.1053/j.jepm.2015.09.001]
[26]
Abenavoli, L.; Capasso, R.; Milic, N.; Capasso, F. Milk thistle in liver diseases: Past, present, future. Phytother. Res., 2010, 24(10), 1423-1432.
[http://dx.doi.org/10.1002/ptr.3207] [PMID: 20564545]
[27]
Vrba, J.; Papoušková, B.; Roubalová, L.; Zatloukalová, M.; Biedermann, D. Křen, V.; Valentová, K.; Ulrichová, J.; Vacek, J. Metabolism of flavonolignans in human hepatocytes. J. Pharm. Biomed. Anal., 2018, 152, 94-101.
[http://dx.doi.org/10.1016/j.jpba.2018.01.048] [PMID: 29414024]
[28]
Fallah, M.; Davoodvandi, A.; Nikmanzar, S.; Aghili, S.; Mirazimi, S.M.A.; Aschner, M.; Rashidian, A.; Hamblin, M.R.; Chamanara, M.; Naghsh, N.; Mirzaei, H. Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer. Biomed. Pharmacother., 2021, 142, 112024.
[http://dx.doi.org/10.1016/j.biopha.2021.112024] [PMID: 34399200]
[29]
Vilahur, G.; Casaní, L.; Peña, E.; Crespo, J.; Juan-Babot, O.; Ben-Aicha, S.; Mendieta, G.; Béjar, M.T.; Borrell, M.; Badimon, L. Silybum marianum provides cardioprotection and limits adverse remodeling post-myocardial infarction by mitigating oxidative stress and reactive fibrosis. Int. J. Cardiol., 2018, 270, 28-35.
[http://dx.doi.org/10.1016/j.ijcard.2018.06.030] [PMID: 29936043]
[30]
Porwal, O.; Mohammed Ameen, M.S.; Anwer, E.T.; Uthirapathy, S.; Ahamad, J.; Tahsin, A. Silybum marianum (Milk Thistle): Review on Its chemistry, morphology, ethno medical uses, phytochemistry and pharmacological activities. J. Drug Deliv. Ther., 2019, 9(5), 199-206.
[http://dx.doi.org/10.22270/jddt.v9i5.3666]
[31]
Zhang, Z.; Zhou, L.; Xie, N.; Nice, E.C.; Zhang, T.; Cui, Y.; Huang, C. Overcoming cancer therapeutic bottleneck by drug repurposing. Signal Transduct. Target. Ther., 2020, 5(1), 113.
[http://dx.doi.org/10.1038/s41392-020-00213-8] [PMID: 32616710]
[32]
de Souza Santos, V.; Peters, B.; Côco, L.Z.; Alves, G.M.; de Assis, A.L.E.M.; Nogueira, B.V.; Meyrelles, S.S.; Porto, M.L.; Vasquez, E.C.; Campagnaro, B.P.; Pereira, T.M.C. Silymarin protects against radiocontrast-induced nephropathy in mice. Life Sci., 2019, 228, 305-315.
[http://dx.doi.org/10.1016/j.lfs.2019.04.061] [PMID: 31047898]
[33]
Bahmani, M.; Shirzad, H.; Rafieian, S.; Rafieian-Kopaei, M. Silybum marianum: beyond hepatoprotection. J. Evid-based Complement. Altern. Med, 2015, 20(4), 292-301.
[34]
Alzoubi, H.K.; Khabour, F.O.; Alkofahi, S.A.; Mhaidat, M.N.; Abu-Siniyeh, A.A. Anticancer and antimutagenic activity of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. against skin cancer induced by DMBA: In vitro and in vivo models. Pak. J. Pharm. Sci., 2021, 34(3), 987-993.
[PMID: 34602423]
[35]
Iqbal, B.; Ali, J.; Ganguli, M.; Mishra, S.; Baboota, S. Silymarin-loaded nanostructured lipid carrier gel for the treatment of skin cancer. Nanomedicine, 2019, 14(9), 1077-1093.
[http://dx.doi.org/10.2217/nnm-2018-0235] [PMID: 31050580]
[36]
Mastron, J.K.; Siveen, K.S.; Sethi, G.; Bishayee, A. Silymarin and hepatocellular carcinoma. Anticancer Drugs, 2015, 26(5), 475-486.
[http://dx.doi.org/10.1097/CAD.0000000000000211] [PMID: 25603021]
[37]
Upadhyay, P.; Bhattacharjee, M.; Bhattacharya, S.; Ahir, M.; Adhikary, A.; Patra, P. Silymarin-loaded, lactobionic acid-conjugated porous PLGA nanoparticles induce apoptosis in liver cancer cells. ACS Appl. Bio Mater., 2020, 3(10), 7178-7192.
[http://dx.doi.org/10.1021/acsabm.0c00987] [PMID: 35019376]
[38]
Zhao, X.; Deng, Y.; Zhang, Y.; Zu, Y.; Lian, B.; Wu, M.; Zu, C.; Wu, W. Silymarin nanoparticles through emulsion solvent evaporation method for oral delivery with high antioxidant activities, bioavailability, and absorption in the liver. RSC Advances, 2016, 6(95), 93137-93146.
[http://dx.doi.org/10.1039/C6RA12896C]
[39]
Bosch-Barrera, J.; Queralt, B.; Menendez, J.A. Targeting STAT3 with silibinin to improve cancer therapeutics. Cancer Treat. Rev., 2017, 58, 61-69.
[http://dx.doi.org/10.1016/j.ctrv.2017.06.003] [PMID: 28686955]
[40]
Hajighasemlou, S.; Farajollahi, M.; Alebouyeh, M.; Rastegar, H.; Manzari, M.T.; Mirmoghtadaei, M.; Moayedi, B.; Ahmadzadeh, M.; Kazemi, M.; Parvizpour, F.; Gharibzadeh, S. Study of the effect of silymarin on viability of breast cancer cell lines. Adv. Breast Cancer Res., 2014, 3(3), 100-105.
[http://dx.doi.org/10.4236/abcr.2014.33015]
[41]
Gheybi, F.; Alavizadeh, S.H.; Rezayat, S.M.; Zendedel, E.; Jaafari, M. Chemotherapeutic activity of Silymarin combined with doxorubicin liposomes in 4T1 breast cancer cells. Nanomed. Res. J., 2019, 4(1), 29-34.
[42]
Xia, Y.; Chang, T.; Wang, Y.; Liu, Y.; Li, W.; Li, M.; Fan, H.Y. YAP promotes ovarian cancer cell tumorigenesis and is indicative of a poor prognosis for ovarian cancer patients. PLoS One, 2014, 9(3), e91770.
[http://dx.doi.org/10.1371/journal.pone.0091770] [PMID: 24622501]
[43]
Lotfi, Z.; Salehi, E.; Morovati-sharifabad, M.; Sarkargar, F.; Pourghanbari, G. The effects of silibinin on SORT1 gene expression and A2780s ovarian cancer cell line viability. IJBSM, 2021, 6(3), 80-85.
[http://dx.doi.org/10.34172/ijbsm.2021.15]
[44]
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]
[45]
Amawi, H.; Hussein, N.A.; Karthikeyan, C.; Manivannan, E.; Wisner, A.; Williams, F.E.; Samuel, T.; Trivedi, P.; Ashby, C.R., Jr; Tiwari, A.K. HM015k, a novel silybin derivative, multi-targets metastatic ovarian cancer cells and is safe in zebrafish toxicity studies. Front. Pharmacol., 2017, 8, 498.
[http://dx.doi.org/10.3389/fphar.2017.00498] [PMID: 28824426]
[46]
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]
[47]
Chipurupalli, S.; Kannan, E. Diverse actions of hypoxia-inducible factor 1 inhibitors in cancer. World J. Pharm. Res., 2018, 8(2), 669-684.
[48]
You, Y.; Chen, L.; Wu, Y.; Wang, M.; Lu, H.; Zhou, X.; Liu, H.; Fu, Z.; He, Q.; Ou, J.; Fu, X.; Liu, Y.; Kwan, H.; Liang, D.; Zhao, X.; Dai, J. Silibinin promotes cell proliferation through facilitating G1/S transitions by activating drp1-mediated mitochondrial fission in cells. Cell Transplant., 2020, 29, 963689720950213.
[http://dx.doi.org/10.1177/0963689720950213] [PMID: 32830544]
[49]
Wu, J.; Chen, C.; Zhao, K.N. Phosphatidylinositol 3-kinase signaling as a therapeutic target for cervical cancer. Curr. Cancer Drug Targets, 2013, 13(2), 143-156.
[http://dx.doi.org/10.2174/1568009611313020004] [PMID: 23297827]
[50]
Imai-Sumida, M.; Chiyomaru, T.; Majid, S.; Saini, S.; Nip, H.; Dahiya, R.; Tanaka, Y.; Yamamura, S. Silibinin suppresses bladder cancer through down-regulation of actin cytoskeleton and PI3K/Akt signaling pathways. Oncotarget, 2017, 8(54), 92032-92042.
[http://dx.doi.org/10.18632/oncotarget.20734] [PMID: 29190895]
[51]
Verma, K.K.; Goyal, S.; Gupta, G.D. Silymarin as herbal medicine- A review. Saudi J. Med. Pharm. Sci, 2018, 4, 36-48.
[52]
Singh, T.; Prasad, R.; Katiyar, S.K. Therapeutic intervention of silymarin on the migration of non-small cell lung cancer cells is associated with the axis of multiple molecular targets including class 1 HDACs, ZEB1 expression, and restoration of miR-203 and E-cadherin expression. Am. J. Cancer Res., 2016, 6(6), 1287-1301.
[PMID: 27429844]
[53]
Cufí, S.; Bonavia, R.; Vazquez-Martin, A.; Oliveras-Ferraros, C.; Corominas-Faja, B.; Cuyàs, E.; Martin-Castillo, B.; Barrajón-Catalán, E.; Visa, J.; Segura-Carretero, A.; Joven, J.; Bosch-Barrera, J.; Micol, V.; Menendez, J.A. Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo. Sci. Rep., 2013, 3(1), 2459.
[http://dx.doi.org/10.1038/srep02459] [PMID: 23963283]
[54]
Zhu, Z.; Sun, G. Silymarin mitigates lung impairments in a rat model of acute respiratory distress syndrome. Inflammopharmacology, 2018, 26(3), 747-754.
[http://dx.doi.org/10.1007/s10787-017-0407-3] [PMID: 29098546]
[55]
Li, W.; Mu, D.; Song, L.; Zhang, J.; Liang, J.; Wang, C.; Liu, N.; Tian, F.; Li, X.; Zhang, W.; Wang, X. Molecular mechanism of silymarin-induced apoptosis in a highly metastatic lung cancer cell line anip973. Cancer Biother. Radiopharm., 2011, 26(3), 317-324.
[http://dx.doi.org/10.1089/cbr.2010.0892] [PMID: 21711112]
[56]
Zhang, Y.; Li, Q.; Ge, Y.; Chen, Y.; Chen, J.; Dong, Y.; Shi, W. Silibinin triggers apoptosis and cell-cycle arrest of SGC7901 cells. Phytother. Res., 2013, 27(3), 397-403.
[http://dx.doi.org/10.1002/ptr.4733] [PMID: 22619007]
[57]
Bittencourt, M.L.F.; Rodrigues, R.P.; Kitagawa, R.R.; Gonçalves, R.C.R. The gastroprotective potential of silibinin against Helicobacter pylori infection and gastric tumor cells. Life Sci., 2020, 256, 117977.
[http://dx.doi.org/10.1016/j.lfs.2020.117977] [PMID: 32603822]
[58]
Arafa Keshk, W.; Zahran, S.M.; Katary, M.A.; Abd-Elaziz Ali, D. Modulatory effect of silymarin on nuclear factor-erythroid-2-related factor 2 regulated redox status, nuclear factor-κB mediated inflammation and apoptosis in experimental gastric ulcer. Chem. Biol. Interact., 2017, 273, 266-272.
[http://dx.doi.org/10.1016/j.cbi.2017.06.022] [PMID: 28648817]
[59]
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]
[60]
Su, C.H.; Chen, L.J.; Liao, J.F.; Cheng, J.T. Increase of phosphatase and tensin homolog by silymarin to inhibit human pharynx squamous cancer. J. Med. Food, 2013, 16(9), 778-784.
[http://dx.doi.org/10.1089/jmf.2012.2534] [PMID: 23909904]
[61]
Choi, E.S.; Oh, S.; Jang, B.; Yu, H.J.; Shin, J.A.; Cho, N.P.; Yang, I.H.; Won, D.H.; Kwon, H.J.; Hong, S.D.; Cho, S.D. Silymarin and its active component silibinin act as novel therapeutic alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling cascade. Cell. Oncol., 2017, 40(3), 235-246.
[http://dx.doi.org/10.1007/s13402-017-0318-8] [PMID: 28401485]
[62]
Gohulkumar, M.; Gurushankar, K.; Rajendra Prasad, N.; Krishnakumar, N. Enhanced cytotoxicity and apoptosis-induced anticancer effect of silibinin-loaded nanoparticles in oral carcinoma (KB) cells. Mater. Sci. Eng. C, 2014, 41, 274-282.
[http://dx.doi.org/10.1016/j.msec.2014.04.056] [PMID: 24907761]
[63]
Yang, C.Y.; Tsao, C.H.; Hsieh, C.C.; Lin, C.K.; Lin, C.S.; Li, Y.H.; Chang, W.C.; Cheng, J.C.; Lin, G.J.; Sytwu, H.K.; Wang, Y.L.; Chen, Y.W. Downregulation of Jumonji-C domain-containing protein 5 inhibits proliferation by silibinin in the oral cancer PDTX model. PLoS One, 2020, 15(7), e0236101.
[http://dx.doi.org/10.1371/journal.pone.0236101] [PMID: 32678829]
[64]
Feng, W.; Cai, D.; Zhang, B.; Lou, G.; Zou, X. Combination of HDAC inhibitor TSA and silibinin induces cell cycle arrest and apoptosis by targeting survivin and cyclinB1/Cdk1 in pancreatic cancer cells. Biomed. Pharmacother., 2015, 74, 257-264.
[http://dx.doi.org/10.1016/j.biopha.2015.08.017] [PMID: 26349994]
[65]
Shukla, S.K.; Dasgupta, A.; Mehla, K.; Gunda, V.; Vernucci, E.; Souchek, J.; Goode, G.; King, R.; Mishra, A.; Rai, I.; Nagarajan, S.; Chaika, N.V.; Yu, F.; Singh, P.K. Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth. Oncotarget, 2015, 6(38), 41146-41161.
[http://dx.doi.org/10.18632/oncotarget.5843] [PMID: 26510913]
[66]
Anestopoulos, I.; Sfakianos, A.; Franco, R.; Chlichlia, K.; Panayiotidis, M.; Kroll, D.; 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]
[67]
Krishna, P.M. Silymarin microspheres and its antiproliferative action on human prostate adenomatous cancer du145 cells. World J. Pharm. Pharm. Sci., 2014, 3(5), 1447-1457.
[68]
Gioti, K.; Papachristodoulou, A.; Benaki, D.; Havaki, S.; Beloukas, A.; Vontzalidou, A.; Aligiannis, N.; Skaltsounis, A.L.; Mikros, E.; Tenta, R. Silymarin enriched extract (Silybum marianum) additive effect on doxorubicin-mediated cytotoxicity in PC-3 prostate cancer cells. Planta Med., 2019, 85(11/12), 997-1007.
[http://dx.doi.org/10.1055/a-0954-6704] [PMID: 31288278]
[69]
Faezizadeh, Z.; Mesbah-Namin, S.; Allameh, A. The effect of silymarin on telomerase activity in the human leukemia cell line K562. Planta Med., 2012, 78(9), 899-902.
[http://dx.doi.org/10.1055/s-0031-1298464] [PMID: 22532022]
[70]
Elyasi, S.; Hosseini, S.; Niazi, M.M.R.; Aledavood, S.A.; Karimi, G. Effect of oral silymarin administration on prevention of radiotherapy induced mucositis: A randomized, double‐blinded, placebo‐controlled clinical trial. Phytother. Res., 2016, 30(11), 1879-1885.
[http://dx.doi.org/10.1002/ptr.5704] [PMID: 27555604]
[71]
Bai, Z.L.; Tay, V.; Guo, S.Z.; Ren, J.; Shu, M.G. Silibinin induced human glioblastoma cell apoptosis concomitant with autophagy through simultaneous inhibition of mTOR and YAP. BioMed Res. Int., 2018, 2018, 6165192.
[http://dx.doi.org/10.1155/2018/6165192]
[72]
Delmas, D.; Xiao, J.; Vejux, A.; Aires, V. Silymarin and cancer: A dual strategy in both in chemoprevention and chemosensitivity. Molecules, 2020, 25(9), 2009.
[http://dx.doi.org/10.3390/molecules25092009] [PMID: 32344919]
[73]
Baradaran, A.; Samadi, F.; Ramezanpour, S.S.; Yousefdoust, S. Hepatoprotective effects of silymarin on CCl4-induced hepatic damage in broiler chickens model. Toxicol. Rep., 2019, 6, 788-794.
[http://dx.doi.org/10.1016/j.toxrep.2019.07.011] [PMID: 31440455]
[74]
Mukhtar, S.; Xiaoxiong, Z.; Qamer, S.; Saad, M.; Mubarik, M.S.; Mahmoud, A.H.; Mohammed, O.B. Hepatoprotective activity of silymarin encapsulation against hepatic damage in albino rats. Saudi J. Biol. Sci., 2021, 28(1), 717-723.
[http://dx.doi.org/10.1016/j.sjbs.2020.10.063] [PMID: 33424359]
[75]
Masarone, M.; Rosato, V.; Dallio, M.; Abenavoli, L.; Federico, A.; Loguercio, C.; Persico, M. Epidemiology and natural history of alcoholic liver disease. Rev. Recent Clin. Trials, 2016, 11(3), 167-174.
[http://dx.doi.org/10.2174/1574887111666160810101202] [PMID: 27515957]
[76]
Abenavoli, L.; Masarone, M.; Federico, A.; Rosato, V.; Dallio, M.; Loguercio, C.; Persico, M. Alcoholic hepatitis: pathogenesis, diagnosis and treatment. Rev. Recent Clin. Trials, 2016, 11(3), 159-166.
[http://dx.doi.org/10.2174/1574887111666160724183409] [PMID: 27457347]
[77]
Nanda, V.; Gupta, V.; Sharma, S.N.; Pasricha, A.; Karmakar, A.K.; Patel, A.; Bhatt, V.M.; Kantroo, B.L.; Kumar, B.; Paul, N.K.; Attam, R. Effect of Liverubin™ on hepatic biochemical profile in patients of alcoholic liver disease: a retrospective study. Minerva Med., 2014, 105, 1-8.
[PMID: 26076375]
[78]
Tighe, S.P.; Akhtar, D.; Iqbal, U.; Ahmed, A. Chronic liver disease and silymarin: A biochemical and clinical review. J. Clin. Transl. Hepatol., 2020, 8(4), 1-5.
[http://dx.doi.org/10.14218/JCTH.2020.00012] [PMID: 33447529]
[79]
Milosević N.; Milanović M.; Abenavoli, L.; Milić N. Phytotherapy and NAFLD-from goals and challenges to clinical practice. Rev. Recent Clin. Trials, 2015, 9(3), 195-203.
[http://dx.doi.org/10.2174/1574887109666141216110337] [PMID: 25514914]
[80]
Solhi, H.; Ghahremani, R.; Kazemifar, A.M.; Hoseini Yazdi, Z. Silymarin in treatment of non-alcoholic steatohepatitis: A randomized clinical trial. Caspian J. Intern. Med., 2014, 5(1), 9-12.
[PMID: 24490006]
[81]
Wah Kheong, C.; Nik Mustapha, N.R.; Mahadeva, S. A randomized trial of silymarin for the treatment of nonalcoholic steatohepatitis. Clin. Gastroenterol. Hepatol., 2017, 15(12), 1940-1949.e8.
[http://dx.doi.org/10.1016/j.cgh.2017.04.016] [PMID: 28419855]
[82]
Curcio, A.; Romano, A.; Cuozzo, S.; Di Nicola, A.; Grassi, O.; Schiaroli, D.; Nocera, G.F.; Pironti, M. Silymarin in combination with vitamin C, vitamin E, coenzyme Q10 and selenomethionine to improve liver enzymes and blood lipid profile in NAFLD patients. Medicina, 2020, 56(10), 544.
[http://dx.doi.org/10.3390/medicina56100544] [PMID: 33080906]
[83]
Esmaeil, N.; Anaraki, S.B.; Gharagozloo, M.; Moayedi, B. Silymarin impacts on immune system as an immunomodulator: One key for many locks. Int. Immunopharmacol., 2017, 50, 194-201.
[http://dx.doi.org/10.1016/j.intimp.2017.06.030] [PMID: 28672215]
[84]
Shahidi, M.; Vaziri, F.; Haerian, A.; Farzanegan, A.; Jafari, S.; Sharifi, R.; Shirazi, F.S. Proliferative and anti-inflammatory effects of resveratrol and silymarin on human gingival fibroblasts: A view to the future. J. Dent., 2017, 14(4), 203-211.
[PMID: 29285030]
[85]
Hussain, S.A.; Jassim, N.A.; Numan, I.T.; Al-Khalifa, I.I.; Abdullah, T.A. Anti-inflammatory activity of silymarin in patients with knee osteoarthritis. A comparative study with piroxicam and meloxicam. Saudi Med. J., 2009, 30(1), 98-103.
[PMID: 19139781]
[86]
Ahmed Aziz, T.; Hasan Marouf, B.; Aorahman Ahmed, Z.; Abdulrahman Hussain, S. Anti-inflammatory activity of silibinin in animal models of chronic inflammation. Am. J. Pharmacol. Sci., 2014, 2(1), 7-11.
[http://dx.doi.org/10.12691/ajps-2-1-2]
[87]
Azadpour, M.; Farajollahi, M.M.; Varzi, A.M.; Hashemzadeh, P.; Mahmoudvand, H.; Barati, M. Extraction, chemical composition, antioxidant property, and in vitro anticancer activity of silymarin from Silybum marianum on Kb and A549 cell lines. Curr. Drug Discov. Technol., 2021, 18(4), 511-517.
[http://dx.doi.org/10.2174/1570163817666200827111127] [PMID: 32860361]
[88]
Al Atraqchi, N.H.; Shaikh Hamed, W.M.A.A. Preliminary phytochemical screening and in vitro evaluation of antioxidant activity of Iraqi species of Silybum marianum seeds. Int. Res. J. Pharm., 2014, 5(5), 378-383.
[http://dx.doi.org/10.7897/2230-8407.050579]
[89]
Serçe, A. Toptancı B.Ç.; Tanrıkut, S.E.; Altaş S.; Kızıl, G.; Kızıl, S.; Kızıl, M. Assessment of the antioxidant activity of Silybum marianum seed extract and its protective effect against DNA oxidation, protein damage and lipid peroxidation. Food Technol. Biotechnol., 2016, 54(4), 455-461.
[http://dx.doi.org/10.17113/ftb.54.04.16.4323] [PMID: 28115903]
[90]
Colturato, C.P.; Constantin, R.P.; Maeda, A.S., Jr; Constantin, R.P.; Yamamoto, N.S.; Bracht, A.; Ishii-Iwamoto, E.L.; Constantin, J. Metabolic effects of silibinin in the rat liver. Chem. Biol. Interact., 2012, 195(2), 119-132.
[http://dx.doi.org/10.1016/j.cbi.2011.11.006] [PMID: 22137898]
[91]
Abenavoli, L.; Milic, N.; Capasso, F. Anti-oxidant therapy in non-alcoholic fatty liver disease: the role of silymarin. Endocrine, 2012, 42(3), 754-755.
[http://dx.doi.org/10.1007/s12020-012-9677-0] [PMID: 22527892]
[92]
Di Pierro, F.; Putignano, P.; Montesi, L.; Moscatiello, S.; Marchesini Reggiani, G.; Villanova, N. Preliminary study about the possible glycemic clinical advantage in using a fixed combination of Berberis aristata and Silybum marianum standardized extracts versus only Berberis aristata in patients with type 2 diabetes. Clin. Pharmacol., 2013, 5, 167-174.
[http://dx.doi.org/10.2147/CPAA.S54308] [PMID: 24277991]
[93]
Ebrahimpour Koujan, S.; Gargari, B.P.; Mobasseri, M.; Valizadeh, H.; Asghari-Jafarabadi, M. Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: A randomized, triple-blind, placebo-controlled clinical trial. Phytomedicine, 2015, 22(2), 290-296.
[http://dx.doi.org/10.1016/j.phymed.2014.12.010] [PMID: 25765835]
[94]
Mohammadi Arvanag, F.; Bayrami, A.; Habibi-Yangjeh, A.; Rahim Pouran, S. A comprehensive study on antidiabetic and antibacterial activities of ZnO nanoparticles biosynthesized using Silybum marianum L. seed extract. Mater. Sci. Eng. C, 2019, 97, 397-405.
[http://dx.doi.org/10.1016/j.msec.2018.12.058] [PMID: 30678925]
[95]
Abed, I.J.; Al-Moula, R.; Abdulhasan, G.A. Antibacterial effect of flavonoids extracted from seeds of Silybum marianum against common pathogenic bacteria. World J. Exp. Biosci., 2015, 3(1), 36-39.
[96]
de Oliveira, D.R.; Tintino, S.R.; Braga, M.F.; Boligon, A.A.; Athayde, M.L.; Coutinho, H.D.; de Menezes, I.R.; Fachinetto, R. In vitro antimicrobial and modulatory activity of the natural products silymarin and silibinin. BioMed Res. Int., 2015, 2015, 292797.
[PMID: 25866771]
[97]
Bajwa, A.; Tariq, S.; Yuchi, A.; Hafeez, R.; Arshad, A.; Zaman, M.; Aqeel, T.; Mushtaq, M.N. Evaluation of anti-bacterial activity of Silybum marianum against pathogenic and resistant bacteria. Eur. J. Med. Chem., 2016, 13(4), 1-7.
[98]
Salamone, F.; Galvano, F.; Marino, A.; Paternostro, C.; Tibullo, D.; Bucchieri, F.; Mangiameli, A.; Parola, M.; Bugianesi, E.; Li Volti, G. Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis. Dig. Liver Dis., 2012, 44(4), 334-342.
[http://dx.doi.org/10.1016/j.dld.2011.11.010] [PMID: 22197629]
[99]
Anestopoulos, I.; Kavo, A.; Tentes, I.; Kortsaris, A.; Panayiotidis, M.; Lazou, A.; Pappa, A. Silibinin protects H9c2 cardiac cells from oxidative stress and inhibits phenylephrine-induced hypertrophy: Potential mechanisms. J. Nutr. Biochem., 2013, 24(3), 586-594.
[http://dx.doi.org/10.1016/j.jnutbio.2012.02.009] [PMID: 22818713]
[100]
Shahbazi, F.; Dashti-Khavidaki, S.; Khalili, H.; Lessan-Pezeshki, M. Potential renoprotective effects of silymarin against nephrotoxic drugs: A review of literature. J. Pharm. Pharm. Sci., 2012, 15(1), 112-123.
[http://dx.doi.org/10.18433/J3F88S] [PMID: 22365093]
[101]
Ullah, H.; Khan, H. Anti-Parkinson potential of silymarin: Mechanistic insight and therapeutic standing. Front. Pharmacol., 2018, 9, 422.
[http://dx.doi.org/10.3389/fphar.2018.00422] [PMID: 29755356]
[102]
Wang, C.; Wang, Z.; Zhang, X.; Zhang, X.; Dong, L.; Xing, Y.; Li, Y.; Liu, Z.; Chen, L.; Qiao, H.; Wang, L.; Zhu, C. Protection by silibinin against experimental ischemic stroke: Up-regulated pAkt, pmTOR, HIF-1α and Bcl-2, down-regulated Bax, NF-κB expression. Neurosci. Lett., 2012, 529(1), 45-50.
[http://dx.doi.org/10.1016/j.neulet.2012.08.078] [PMID: 22999929]
[103]
Sayyah, M.; Boostani, H.; Pakseresht, S.; Malayeri, A. Comparison of Silybum marianum (L.) Gaertn. with fluoxetine in the treatment of obsessive-compulsive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2010, 34(2), 362-365.
[http://dx.doi.org/10.1016/j.pnpbp.2009.12.016] [PMID: 20035818]
[104]
Behl, A.; Swami, G.; Sircar, S.S.; Bhatia, M.S.; Banerjee, B.D. Relationship of possible stress-related biochemical markers to oxidative/antioxidative status in obsessive-compulsive disorder. Neuropsychobiology, 2010, 61(4), 210-214.
[http://dx.doi.org/10.1159/000306591] [PMID: 20389131]
[105]
Nazir, N.; Karim, N.; Abdel-Halim, H.; Khan, I.; Wadood, S.F.; Nisar, M. Phytochemical analysis, molecular docking and antiamnesic effects of methanolic extract of Silybum marianum (L.) Gaertn seeds in scopolamine induced memory impairment in mice. J. Ethnopharmacol., 2018, 210, 198-208.
[http://dx.doi.org/10.1016/j.jep.2017.08.026] [PMID: 28842342]
[106]
Peila, C.; Coscia, A.; Tonetto, P.; Spada, E.; Milani, S.; Moro, G.; Fontana, C.; Vagliano, L.; Tortone, C.; Di Bella, E.; Bertino, E.; Bertino, E. Evaluation of the galactogogue effect of silymarin on mothers of preterm newborns (<32 weeks). Pediatr. Med. Chir., 2015, 37(3), 105.
[http://dx.doi.org/10.4081/pmc.2015.105] [PMID: 26714778]
[107]
Olagaray, K.E.; Bradford, B.J. Plant flavonoids to improve productivity of ruminants – A review. Anim. Feed Sci. Technol., 2019, 251, 21-36.
[http://dx.doi.org/10.1016/j.anifeedsci.2019.02.004]
[108]
Serviddio, G.; Bellanti, F.; Stanca, E.; Lunetti, P.; Blonda, M.; Tamborra, R.; Siculella, L.; Vendemiale, G.; Capobianco, L.; Giudetti, A.M. Silybin exerts antioxidant effects and induces mitochondrial biogenesis in liver of rat with secondary biliary cirrhosis. Free Radic. Biol. Med., 2014, 73, 117-126.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.05.002] [PMID: 24819445]
[109]
Trakulsrichai, S.; Sriapha, C.; Tongpoo, A.; Udomsubpayakul, U.; Wongvisavakorn, S.; Srisuma, S.; Wananukul, W. Clinical characteristics and outcome of toxicity from Amanita mushroom poisoning. Int. J. Gen. Med., 2017, 10, 395-400.
[http://dx.doi.org/10.2147/IJGM.S141111] [PMID: 29138589]
[110]
Santi, L.; Maggioli, C.; Mastroroberto, M.; Tufoni, M.; Napoli, L.; Caraceni, P. Acute liver failure caused by Amanita phalloides poisoning. Int. J. Hepatol., 2012, 2012, 487480.
[111]
Mengs, U.; Torsten Pohl, R.; Mitchell, T. Legalon® SIL: the antidote of choice in patients with acute hepatotoxicity from amatoxin poisoning. Curr. Pharm. Biotechnol., 2012, 13(10), 1964-1970.
[http://dx.doi.org/10.2174/138920112802273353] [PMID: 22352731]

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