The Effect of Silymarin in Milk Thistle on Lipid Profile, Liver Enzymes and Inflammatory Cytokines in the Blood of Male Wistar Rats
Subject Areas : Journal of Animal BiologyHoda Jahangiri 1 , Parichehreh Yaghmaei 2 , Azade Ebrahim Habibi 3 , Shahrbanoo Oryan 4
1 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
3 - Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, 1411713137, Tehran, Iran
4 - Department of Biology, Faculty of Biological Science, Kharazmi University, Tehran, Iran
Keywords: Milk thistle, Alpha-amylase, Cytokine, Liver enzymes, Lipid profile, Silybum marianum.,
Abstract :
Milk thistle (Silybum marianum) is a medicinal plant with anti-inflammatory and antioxidant properties and in the treatment of chronic liver and inflammatory diseases that grows in the Mediterranean region. This study aimed to investigate the effect of silymarin in milk thistle on lipid profile, liver enzymes, and inflammatory cytokines in the blood of male Wistar rats. First, 16 adult rats with an average weight of 180-200 grams were selected and treated with silymarin and accumulated alpha-amylase. Then, by comparing with the control sample, the profile of triglycerides, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and also, inflammatory cytokines interleukin 6 (IL-6), interleukin 1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NFKB) and C-reactive protein (CRP) with kits specificity and ELISA method were assessed. Data analyzed using ANOVA and Tukey's post hoc tests by the SPSS software. Based on the results, the group treated with silymarin dissolved in 1% dimethyl sulfoxide and agglomerated alpha-amylase showed a significant reduction effect on the level of inflammatory cytokines, liver enzymes, LDL, triglycerides, and cholesterol and also a significant increase in HDL in the blood, compared to other groups. It is concluded that silymarin can potentially protect the liver by modulating the level of liver enzymes. By reducing the lipid profile and inflammatory factors in the blood, it plays an important role in reducing diseases related to the liver, cardiovascular, and immune system, further research should determines the optimal doses and areas and the individual characteristics of the patient and underlying diseases.
1. Nawaz A, Zaib S, Khan I, Ahmed A, Shahzadi K, Riaz H. Silybum marianum: An overview of its phytochemistry and pharmacological activities with emphasis on potential anticancer properties. Anticancer Agents Med Chem. 2023;23(13):1519-1534.
2. Dwyer JT, Coates PM, Smith MJ. Dietary supplements: regulatory challenges and research resources. Nutrients. 2018; 10(1):41.
3. Fanoudi S, Alavi MS, 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.
4. Achufusi TGO, Pellegrini MV, Patel RK. Milk Thistle. [Updated 2024 Feb 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from:https://www.ncbi.nlm.nih.gov/books/NBK541075/.
5. Surai PF, Surai A. Silymarin and NF-κB. Wageningen Academic Publishers: Wageningen, The Netherlands. 2023:151-177.
6. Ali SO, Darwish HA, Ismail NA. Curcumin, Silybin Phytosome® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production. Basic Clin Pharmacol Toxicol. 2016;118(5):369-380.
7. García-Muñoz AM, Victoria-Montesinos D, Ballester P, Cerdá B, Zafrilla P. A Descriptive Review of the Antioxidant Effects and Mechanisms of Action of Berberine and Silymarin. Molecules. 2024; 29(19):4576.
8. MI H. Therapeutic roles of silymarin or/and Taurine on nonalcoholic fatty liver disease associated with metabolic syndrome in rats. J Sci Res Sci. 2015;32(2):283-310.
9. Dutta S, Mishra SP, Sahu AK, Mishra K, Kashyap P, Sahu B. Hepatocytes and their role in metabolism. Drug Metab. 2021; http://dx.doi.org/10.5772/intechopen.99083
10. Giashuddin S, Alawad M. Histopathological diagnosis of nonalcoholic steatohepatitis (NASH). Methods Mol Biol. 2022;2455:1-18.
11. Kheirandish V, Mard-Soltani M, Mojab F, Shakerian N, Nanaie F. The effect of milk thistle, green tea, and cinnamon beverages on liver enzymes of operating room Anesthesia personnel. J Adv Immunopharmacol. 2023;3(1):e136000.
12. Rahmati F, Hosseini SS, Mahuti Safai S, Asgari Lajayer B, Hatami M. New insights into the role of nanotechnology in microbial food safety. 3 Biotech. 2020;10(10):425.
13. Rahmati F. Microencapsulation of Lactobacillus acidophilus and Lactobacillus plantarum in Eudragit S100 and alginate chitosan under gastrointestinal and normal conditions. Appl Nanosci. 2020;10(2):391-399.
14. Mirzaei E, Sabetian G, Masjedi M, Heidari R, Mirjalili M, Dehghanian A, et al. The effect of silymarin on liver enzymes and antioxidant status in trauma patients in the intensive care unit: a randomized double blinded placebo-controlled clinical trial. Clin Exp Hepatol. 2021;7(2):149-155.
15. El-Kamary SS, Shardell MD, Abdel-Hamid M, Ismail S, El-Ateek M, Metwally M, et al. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Phytomedicine. 2009;16(5):391-400.
16. Ahmed S, Ullah N, Parveen S, Javed I, Jalil NAC, Murtey MD, et al. Effect of silymarin as an adjunct therapy in combination with sofosbuvir and ribavirin in hepatitis C patients: a miniature clinical trial. Oxid Med Cell Longev. 2022; 2022(1):9199190.
17. Jamalian M, Mahmodiyeh B, Saveiee S, Solhi H. Investigating the impact of silymarin on liver oxidative injury. J Famil Med Prim Care. 2020;9(3):1707-1711.
18. Martinez EC, Herrera D, Mogan S, Hameed Z, Jangda AA, Khan TJ, et al. Impact of silymarin supplements on liver enzyme levels: a systematic review. Cureus. 2023;15(10):e47608.
19. Hong M, Li S, Tan HY, Wang N, Tsao SW, Feng Y. Current status of herbal medicines in chronic liver disease therapy: the biological effects, molecular targets and future prospects. Int J Mol Sci. 2015;16(12): 28705-28745.
20. Singh D, Cho WC, Upadhyay G. Drug-induced liver toxicity and prevention by herbal antioxidants: an overview. Front Physiol. 2016;6:363.
21. Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. “Silymarin”, a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci. 2011;14(4):308.
22. Rahmati F. Characterization of Lactobacillus, Bacillus and Saccharomyces isolated from Iranian traditional dairy products for potential sources of starter cultures. AIMS Microbio. 2017;3(4):815.
23. Gobalakrishnan S, Asirvatham SS, Janarthanam V. Effect of silybin on lipid profile in hypercholesterolaemic rats. J Clin Diagn Res. 2016;10(4):FF01.
24. Mohammadi H, Hadi A, Arab A, Moradi S, Rouhani MH. Effects of silymarin supplementation on blood lipids: A systematic review and meta‐analysis of clinical trials. Phytother Res. 2019; 33(4):871-880.
25. Mohebbati R, Momeni-Moghaddam MA, Asghari R, Abbasnezhad A, Bideskan AEZ, Salarbashi D, et al. The comparison of the effects of nano-silymarin and silymarin on high-fat diet-induced fatty liver of adult male rats. Avicenna J Phytomed. 2024;14(3):365.
26. Metwally M, El-Gellal A, El-Sawaisi S. Effects of silymarin on lipid metabolism in rats. World Appl Sci J. 2009;6(12):1634-1637.
27. Alharbi KS, Afzal O, Kazmi I, Shaikh MAJ, Thangavelu L, Gulati M, et al. Nuclear factor-kappa B (NF-κB) inhibition as a therapeutic target for plant nutraceuticals in mitigating inflammatory lung diseases. Chem-Biol Interact. 2022;354:109842.
28. Ou Q, Weng Y, Wang S, Zhao Y, Zhang F, Zhou J, et al. Silybin alleviates hepatic steatosis and fibrosis in NASH mice by inhibiting oxidative stress and involvement with the Nf-κB pathway. Dig Dis Sci. 2018; 63:3398-3408.
29. Zhang B, Wang B, Cao S, Wang Y, Wu D. Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation. Int J Mol Med. 2017; 39(5):1111-1118.
30. Farzanegan A, Shokuhian M, Jafari S, Shirazi FS, Shahidi M. Anti-histaminic effects of resveratrol and silymarin on human gingival fibroblasts. Inflammation. 2019;42:1622-1629.
31. Kang JS, Park S-K, Yang K-H, Kim HM. Silymarin inhibits TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells. FEBS Lett. 2003;550(1-3):89-93.
32. Kim EJ, Lee MY, Jeon YJ. Silymarin inhibits morphological changes in LPS-stimulated macrophages by blocking NF-κB pathway. Korean J Physiol Pharmacol. 2015;19(3):211-218.
33. Balouchi S, Gharagozloo M, Esmaeil N, Mirmoghtadaei M, Moayedi B. Serum levels of TGFβ, IL-10, IL-17, and IL-23 cytokines in β-thalassemia major patients: the impact of silymarin therapy. Immunopharmacol Immunotoxicol. 2014;36(4):271-274.
34. Elahi ME, Elieh-Ali-Komi D, Goudarzi F, Mohammadi‑Noori E, Assar S, Shavandi M, et al. Effects of silymarin as adjuvant drug on serum levels of CTRP3, anti-cyclic citrullinated peptide (CCP), and high-sensitivity C-reactive protein (hs-CRP) in rheumatoid arthritis patients. Mol Biol Res Commun. 2024;13(3):137-145.
35. Gargari BP, 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.
36. Shavandi M, Yazdani Y, Asar S, Mohammadi A, Mohammadi-Noori E, Kiani A. The Effect of Oral Administration of Silymarin on Serum Levels of Tumor Necrosis Factor-α and Interleukin-1ß in Patients with Rheumatoid Arthritis. Iran J Immunol. 2022;19(4):427-435.
37. Jaffar HM, Bader ul Ain H, Tufail T, Hanif A, Malik T. Impact of silymarin‐supplemented cookies on liver enzyme and inflammatory markers in non‐alcoholic fatty liver disease patients. Food Sci Nutr. 2024; 12(10):7273-7286.
38. Xiao F, Gao F, Zhou S, Wang L. The therapeutic effects of silymarin for patients with glucose/lipid metabolic dysfunction: A meta-analysis. Medicine. 2020;99(40): e22249.
39. Chen J, Li D-L, Xie L-N, Ma Y-r, Wu P-P, Li C, et al. Synergistic anti-inflammatory effects of silibinin and thymol combination on LPS-induced RAW264. 7 cells by inhibition of NF-κB and MAPK activation. Phytomedicine. 2020;78:153309.
40. Sherif IO, Al-Gayyar M. Antioxidant, anti-inflammatory and hepatoprotective effects of silymarin on hepatic dysfunction induced by sodium nitrite. Eur Cytokine Netw. 2013;24(3):114-121.
41. Toklu HZ, Akbay TT, Velioglu-Ogunc A, Ercan F, Gedik N, Keyer-Uysal M, et al. Silymarin, the antioxidant component of Silybum marianum, prevents sepsis-induced acute lung and brain injury. J Surg Res. 2008;145(2):214-222.
42. Celep NA, Erbaş E, Kara H, Kara A. Silymarin Reduces Paclitaxel-induced Lung Damage Via Down-regulating P2X7R Expression and Inhibiting Inflammation and Apoptosis in the Rats. Pak Vet J. 2024; 44(1):169-175.
43. Jin Y, Zhao X, Zhang H, Li Q, Lu G, Zhao X. Modulatory effect of silymarin on pulmonary vascular dysfunction through HIF-1α-iNOS following rat lung ischemia-reperfusion injury. Exp Therap Med. 2016;12(2):1135-1140.
44. Li D, Hu J, Wang T, Zhang X, Liu L, Wang H, et al. Silymarin attenuates cigarette smoke extract-induced inflammation via simultaneous inhibition of autophagy and ERK/p38 MAPK pathway in human bronchial epithelial cells. Sci Rep. 2016; 6(1):37751.