Developing Rp-Hplc Method and Determination in Vitro Cytotoxicity of Silymarin Obtained From Silybum marinum Plant


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DOI:

https://doi.org/10.5281/zenodo.13939065

Keywords:

HPLC, Silybum marianum, silymarin, cytotoxicity

Abstract

The Asteraceae family's Silybum marinum plant, commonly known as thistle, yields silymarin in its seeds. A frequently employed hepato-protective treatment for conditions like cirrhosis, fatty liver due to alcohol and hazardous chemicals, and hepatitis is silymarin. Conventional milk thistle extract is derived from seeds containing a silymarin content of 4-6%. The extract has 20–35% fatty acids, including linoleic acid, and 65–80% silymarin (a flavonolignan complex). Silymarin constitutes a complex blend of polyphenolic compounds that also contains a flavonoid (taxifolin) and seven closely related flavonolignans (silybin A, silybin B, isosilybin A, isosilybin B, silychristin, silychristin, and silydianin). The two main diastereoisomers of silymarin, silybin A and silybin B, are approximately equally mixed in silibinin, a semi-purified fraction of silymarin. The impact of silymarin on liver, pancreatic, prostate, and skin cancers has been the subject of numerous patents. Owing to silymarin's antioxidant and anti-inflammatory properties, and its ability to modulate various proteins and genes, silymarin exhibits antichemopreventive effects. Moreover, silymarin mitigates the damaging effects on healthy cells or organs. Consequently, silymarin holds potential as an adjuvant therapy for cancer. In this study, the cytotoxicity of silymarin extracts obtained via the HPLC technique—known for its sensitivity, utility, and established efficacy in determining silymarin quantity from the Silybum marianum plant—was assessed using a colorimetric test on A-549 cells. It was found that 100 µM was the LD50 when silymarin was administered to A-549 cells in dosages of 25, 50, 75, and 100 µM.

References

Antika, L.D., Dewi, R.M., 2021. The pharmacological properties of silymarin and its constituents. Natural Product Sciences, 27(2): 68-77.

Azmir, J., Zaidul, I.S.M., Rahman, M.M., Sharif, K.M., Mohamed, A., Sahena, F., Omar, A.K.M., 2013. Techniques for extraction of bioactive compounds from plant materials: A review. Journal of food engineering, 117(4): 426-436.

Bartolome, A.P., Villaseñor I.M., Yang, W.C., 2013. Bidens pilosa L. (Asteraceae): Botanical properties, traditional uses, phytochemistry and pharmacology. Evidence-based complementary and alternative medicine, 51.

Bayram, D., 2017. Silibinin in vitro ortamda CCL-228-SW 480 kolon kanseri hücre hattı üzerine apoptotik etkisinin araştırılması. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi, 8(2): 1-7.

Bijak, M., Synowiec, E., Sitarek, P., Sliwiński, T., Saluk-Bijak, J., 2017. Evaluation of the cytotoxicity and genotoxicity of flavonolignans in different cellular models. Nutrients, 9(12): 1356.

Chambers, C.S., Holečková, V., Petrásková, L., Biedermann, D., Valentová, K., Buchta, M., Křen, V., 2017. The silymarin composition and why does it matter???. Food Research International, 100(3): 339-353.

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., 2005. Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. Cancer Research, 65(10): 4448-57.

Delmas, D., 2020. Silymarin and derivatives: from biosynthesis to health benefits. Molecules, 25(10): 2415.

El Menshawe, S.F., Ahmed, A.S., Abdelaty, L.N., Aboseif, M.A., 2014. Study of hepatoprotective effect of silymarin and ursodeoxycholic acid in chronic Hepatitis C Patients. Medicine Science, 3(4): 1655-1674.

Emadi, S. A., Rahbardar, M. G., Mehri, S., and Hosseinzadeh, H., (2022). A review of therapeutic potentials of milk thistle (Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents. Iranian Journal of Basic Medical Sciences, 25(10):1166.

Eser, N., Göçmen, C., Erdoğan, Ş., Büyüknacar, H.S.G., Kumcu, E.K., Açıkalın, A., Önder, S., 2012. Effect of silymarin on bladder overactivity in cyclophosphamide-induced cystitis rat model. Phytomedicine,19(8-9): 840-845.

Fraschini, F., Demartini, G., Esposti, D., 2002. Pharmacology of silymarin. Clinical Drug ınvestigation, 22: 51-65.

Gheybi, F., Alavizadeh, S.H., Rezayat, S. M., Zendedel, E., Jaafari, M., 2019. Chemotherapeutic activity of Silymarin combined with doxorubicin liposomes in 4T1 breast cancer cells. Nanomedicine Research Journal, 4(1): 29-34.

Giordano, M., Luongo, G., Davinelli, S., Ladhari, A., Nappo, G.R., Giordano, M., 2021. Silybum marianum: not Just Silymarin and Flavonolignans. Records of Natural Products,15(4),

Karabegović, I.T., Stojičević, S.S., Veličković, D.T., Nikolić, N.Č., Lazić, M. L., 2018. Direct ultrasound-assisted extraction and characterization of phenolic compounds from fresh houseleek (Sempervivum marmoreum L.) leaves. Hemijska industrija, 72(1): 13-21.

Karimi, G., Vahabzadeh, M., Lari, P., Rashedinia, M., Moshiri, M., 2011. “Silymarin”, a promising pharmacological agent for treatment of diseases. Iranian Journal of Basic Medical Sciences, 14(4): 308.

Kim, S.H., Choo, G.S., Yoo, E.S., Woo, J.S., Lee, J.H., Han, S.H., Jung, J.Y., 2021. Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis. Oncology Letters, 21(6): 1-10.

Koltai, T., Fliegel, L., 2022. Role of silymarin in cancer treatment: facts, hypotheses, and questions. Journal of Evidence-Based Integrative Medicine, 27: 2515690X211068826.

Lalani, S.S., Anasir, M.I., Poh, C.L., 2020. Antiviral activity of silymarin in comparison with baicalein against EV-A71. BMC Complementary Medicine and Therapies, 20(97): 1-12.

Li, W., Mu, D., Song, L., Zhang, J., Liang, J., Wang, C., Wang, X., 2011. Molecular mechanism of silymarin-induced apoptosis in a highly metastatic lung cancer cell line anip973. Cancer Biotherapy and Radiopharmaceuticals, 26(3): 317-

Manikandan, J., Raffiea Baseri, J., 2022. Green Synthesized Fe3O4 Nanoparticles as Silymarin Drug Carrier and their Anticancer Activity against Liver-HepG2 and Lung-A549 Cancer Cells. Asian Journal of Chemistry, 34(9): 2363-2372.

Polyak, S.J., Ferenci, P., Pawlotsky, J.M., 2013. Hepatoprotective and antiviral functions of silymarin components in hepatitis C virus infection. Hepatology, 57(3): 1262-1271.

Sezer, C.V., 2021. An in vitro assessment of the cytotoxic and apoptotic potency of silymarin and silymarin loaded solid lipid nanoparticles on lung and breast cancer cells. Pakistan Journal of Zoology, 53(4):1407-1415.

Surai, P.F., 2015. Silymarin as a natural antioxidant: An overview of the current evidence and perspectives. Antioxidants, 4(1): 204–247.

Teng, Y.C., Shen, Z.Q., Kao, C.H., Tsai, T.F., 2016. Hepatocellular carcinoma mouse models: Hepatitis B virus-associated hepatocarcinogenesis and haploinsufficient tumor suppressor genes. World Journal of Gastroenterology, 22(1): 300.

Vaidya, A., Roy A., Chaguturu, R., 2018. How to rekindle drug discovery process through integrative therapeutic targeting? Expert Opinion on Drug Discover, 13(10): 893-898.

Vargas-Mendoza, N., Angeles-Valencia, M., Morales-González, Á., Morales-Martínez, M., Madrigal-Bujaidar, E., Álvarez-González, I., Morales-González, J.A., 2021. Effect of silymarin supplementation in lung and liver histological modifications during exercise training in a rodent model. Journal of Functional Morphology and Kinesiology, 6(3): 72.

Wang, Y., Yuan, A.J., Wu, Y.J., Wu, L.M., Zhang, L., 2023. Silymarin in cancer therapy: Mechanisms of action, protective roles in chemotherapy-induced toxicity, and nanoformulations. Journal of Functional Foods, 100: 105384.

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Published

2024-10-16

How to Cite

AKBEL , E., BULDUK , İbrahim, & KARABAĞ , F. (2024). Developing Rp-Hplc Method and Determination in Vitro Cytotoxicity of Silymarin Obtained From Silybum marinum Plant. MAS Journal of Applied Sciences, 9(Özel Sayı), 899–906. https://doi.org/10.5281/zenodo.13939065

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