Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: a randomized, double-blind, placebo controlled trial
Open accessAbstract
The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease and may be a treatment for NASH due to its antioxidant properties. We aimed to assess the safety and efficacy of higher than customary doses of silymarin in non-cirrhotic patients with NASH. This exploratory randomized double-blind placebo controlled multicenter Phase II trial tested a proprietary standardized silymarin preparation (Legalon®, Rottapharm|Madaus, Mylan) and was conducted at 5 medical centers in the United States. Eligible adult patients had liver biopsy within 12 months showing NASH without cirrhosis with NAFLD Activity Score (NAS) ≥4 per site pathologist's assessment. Participants were randomized to Legalon® 420 mg, 700 mg, or placebo t.i.d. for 48 weeks. The primary endpoint was histological improvement ≥2 points in NAS. Of 116 patients screened, 78 were randomized. There were no significant differences in adverse events among the treatment groups. After 48-50 weeks, 4/27 (15%) in the 700 mg dose, 5/26 (19%) participants randomized to 420 mg, and 3/25 (12%) of placebo recipients reached the primary endpoint (p = 0.79) among all randomized participants, indicating no benefit from silymarin in the intention to treat analysis Review by a central pathologist demonstrated that a substantial number of participants (49, 63%) did not meet histological entry criteria and that fibrosis stage improved most in the placebo treated group, although not significantly different from other groups. Silymarin (Legalon®) at the higher than customary doses tested in this study is safe and well tolerated. The effect of silymarin in patients with NASH remains inconclusive due to the substantial number of patients who entered the study but did not meet entry histological criteria, the lack of a statistically significant improvement in NAS of silymarin treated patients, and the unanticipated effect of placebo on fibrosis indicate the need for additional clinical trials. Trial Registration: clinicaltrials.gov, Identifier: NCT00680407.
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Silymarin may improve liver enzymes but the few small RCTs available did not document histological improvement.
“Silymarin (an extract of milk thistle) may improve liver enzymes but the few, small, RCTs available 395,396 did not document histological improvement.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [396]
The Discussion (page not provided) says this trial found no statistically significant histological improvement in NASH, supporting that part of the claim. But it reports no meaningful change in ALT or AST, and notes that another RCT found reduced hepatic fibrosis on histology. Thus this source does not support the suggested enzyme benefit or the blanket statement that the RCTs documented no histological improvement. (LLM, conf=0.87)
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Cites
Design and validation of a histological scoring system for nonalcoholic fatty liver disease†
Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O. W., Ferrell, L. D., Liu, Y., Torbenson, M. S., Unalp‐Arida, A., et al. (2005) · Hepatology · doi:10.1002/hep.20701 · Cited by 10,791 · see citing works
Self-citationNonalcoholic Steatohepatitis: A Proposal for Grading and Staging The Histological Lesions
Brunt, E. M., Janney, C. G., Di Bisceglie, A. M., Neuschwander-Tetri, B. A., & Bacon, B. R. (1999) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.1999.01377.x · Cited by 3,907 · see citing works
Self-citationNeuschwander-Tetri, B. A., Loomba, R., Sanyal, A. J., Lavine, J. E., Van Natta, M. L., Abdelmalek, M. F., Chalasani, N., Dasarathy, S., Diehl, A. M., Hameed, B., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61933-4 · Cited by 2,237 · see citing works
Self-citationThe Use of Silymarin in the Treatment of Liver Diseases
Saller, R., Meier, R. F., & Brignoli, R. (2001) · Drugs · doi:10.2165/00003495-200161140-00003 · Cited by 720 · see citing works
Milk thistle in liver diseases: past, present, future
Abenavoli, L., Capasso, R., Milić, N., & Capasso, F. (2010) · Phytotherapy Research · doi:10.1002/ptr.3207 · Cited by 614 · see citing works
Molecular Virology of Hepatitis B Virus
LOCARNINI, S. A. (2004) · Seminars in Liver Disease · doi:10.1055/s-2004-828672 · Cited by 515 · see citing works
(2004) · Seminars in Liver Disease · doi:10.1055/s-2004-823098 · Cited by 481 · cited 1× · see citing works
“Liver biopsy remains the gold standard for diagnosing and assessing the degree of injury in NASH [1,2].”
BackgroundSelf-citationA randomized trial of silymarin for the treatment of nonalcoholic steatohepatitis
Wah Kheong, C., Nik Mustapha, N. R., & Mahadeva, S. (2017) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2017.04.016 · Cited by 264 · see citing works
Scavenging of reactive oxygen species by silibinin dihemisuccinate
Mira, L., Silva, M. M. P., & Manso, C. (1994) · Biochemical Pharmacology · doi:10.1016/0006-2952(94)90053-1 · Cited by 192 · see citing works
Fried, M. (2012) · JAMA · doi:10.1001/jama.2012.8265 · Cited by 160 · see citing works
Self-citationBosisio, E. (1992) · Pharmacological Research · doi:10.1016/1043-6618(92)91383-r · Cited by 158 · see citing works
Hawke, R. L., Schrieber, S. J., Soule, T. A., Wen, Z., Smith, P. C., Reddy, K. R., Wahed, A. S., Belle, S. H., Afdhal, N. H., Navarro, V. J., et al. (2009) · The Journal of Clinical Pharmacology · doi:10.1177/0091270009347475 · Cited by 143 · see citing works
Self-citationLipid peroxidation and irreversible damage in the rat hepatocyte model
Carini, R., Comoglio, A., Albano, E., & Poli, G. (1992) · Biochemical Pharmacology · doi:10.1016/0006-2952(92)90168-i · Cited by 115 · see citing works
The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease
Zhong, S., Fan, Y., Yan, Q., Fan, X., Wu, B., Han, Y., Zhang, Y., Chen, Y., Zhang, H., & Niu, J. (2017) · Medicine · doi:10.1097/md.0000000000009061 · Cited by 105 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R. (2023) · Hepatology · doi:10.1097/hep.0000000000000323 · Cited by 2,667 · see citing works
Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210 · see citing works
(2024) · Obesity Facts · doi:10.1159/000539371 · Cited by 510 · see citing works
Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review
Bovi, A. P. D., Marciano, F., Mandato, C., Siano, M., Savoia, M., & Vajro, P. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.595371 · Cited by 300 · see citing works
Ferro, D., Baratta, F., Pastori, D., Cocomello, N., Colantoni, A., Angelico, F., & Ben, M. D. (2020) · Nutrients · doi:10.3390/nu12092762 · Cited by 199 · see citing works
Mechanistic Insights into the Pharmacological Significance of Silymarin
Wadhwa, K., Pahwa, R., Kumar, M., Kumar, S., Sharma, P. C., Singh, G., Verma, R., Mittal, V., Singh, I., Kaushik, D. K., et al. (2022) · Molecules · doi:10.3390/molecules27165327 · Cited by 180 · see citing works
Lazebnik, L. B., Голованова, Е. В., Туркина, С. В., Raikhelson, K. L., Okovityy, S. V., Drapkina, O. M., Maev, I. V., Ai, M., Ройтберг, Г. Е., Khlynova, O. V., et al. (2021) · Экспериментальная и клиническая гастроэнтерология · doi:10.31146/1682-8658-ecg-185-1-4-52 · Cited by 155 · see citing works
Aghemo, A., Alekseeva, O. P., Angelico, F., Бакулин, И. Г., Бакулина, Н. В., Bordin, D. S., Bueverov, A. O., Drapkina, O. M., Gillessen, A., Kagarmanova, E. M., et al. (2022) · Annals of Medicine · doi:10.1080/07853890.2022.2069854 · Cited by 135 · see citing works
Evolving Role for Pharmacotherapy in NAFLD/NASH
Attia, S. L., Softic, S., & Mouzaki, M. (2020) · Clinical and Translational Science · doi:10.1111/cts.12839 · Cited by 130 · see citing works
Li, H., Gan, R., Shang, A., Mao, Q., Quan-cai, S., Wu, D., Geng, F., He, X.-Q., & Li, H. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6621644 · Cited by 108 · see citing works
Roeb, E., Canbay, A. E., Tacke, F., Bantel, H., Bojunga, J., de Laffolie, J., Demir, M., Denzer, U. W., Geier, A., Hofmann, W. P., et al. (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1880-2283 · Cited by 102 · see citing works
Current Options and Future Directions for NAFLD and NASH Treatment
Zhang, C., & Yang, M. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147571 · Cited by 94 · see citing works
Majzoub, A. M., Nayfeh, T., Barnard, A., Munaganuru, N., Dave, S., Singh, S., Murad, M. H., & Loomba, R. (2021) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.16583 · Cited by 92 · see citing works
Xanthakos, S. A., Ibrahim, S. H., Adams, K. H., Kohli, R., Sathya, P., Sundaram, S. S., Vos, M. B., Dhawan, A., Caprio, S., Behling, C. A., et al. (2025) · Hepatology · doi:10.1097/hep.0000000000001368 · Cited by 86 · see citing works
Yang, K., Chen, J., Zhang, T., Yuan, X., Ge, A., Wang, S., Xu, H., Zeng, L., & Ge, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.949746 · Cited by 85 · see citing works
Steatotic Liver Disease: Pathophysiology and Emerging Pharmacotherapies
Kokkorakis, M., Muzurović, E. M., Volčanšek, Š., Chakhtoura, M., Hill, M. A., Mikhailidis, D. P., & Mantzoros, C. S. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.123.001087 · Cited by 77 · see citing works
Promising hepatoprotective agents from the natural sources: a study of scientific evidence
Pandey, B., Baral, R., Kaundinnyayana, A., & Panta, S. (2023) · Egyptian Liver Journal · doi:10.1186/s43066-023-00248-w · Cited by 74 · see citing works
Antioxidant and anti-inflammatory agents in chronic liver diseases: Molecular mechanisms and therapy
Zhang, C., Liu, S., & Yang, M. J. (2023) · World Journal of Hepatology · doi:10.4254/wjh.v15.i2.180 · Cited by 71 · see citing works
Mahjoubin‐Tehran, M., Vincentis, A. D., Mikhailidis, D. P., Atkin, S. L., Mantzoros, C. S., Jamialahmadi, T., & Sahebkar, A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101049 · Cited by 70 · see citing works
Kalopitas, G., Antza, C., Doundoulakis, I., Siargkas, A., Kouroumalis, E., Germanidis, G. S., Samara, M. T., & Chourdakis, M. (2020) · Nutrition · doi:10.1016/j.nut.2020.111092 · Cited by 66 · see citing works
A Molecular Insight into the Role of Antioxidants in Nonalcoholic Fatty Liver Diseases
Ezhilarasan, D., & Thangavelu, L. P. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/9233650 · Cited by 63 · see citing works
Tang, R., Li, R., Li, H., Ma, X., Du, P., Yu, X.-Y., Ren, L., Wang, L., & Zheng, W. (2021) · ACS Nano · doi:10.1021/acsnano.1c02158 · Cited by 54 · see citing works
The Potential Application of Chinese Medicine in Liver Diseases: A New Opportunity
Fu, K., Wang, C., Ma, C., Zhou, H., & Li, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.771459 · Cited by 53 · see citing works
Efficacy and safety of anti-hepatic fibrosis drugs
Damiris, K., Tafesh, Z., & Pyrsopoulos, N. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i41.6304 · Cited by 52 · see citing works
Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis
Li, S., Duan, F., Li, S., & Lu, B. (2023) · Annals of Hepatology · doi:10.1016/j.aohep.2023.101174 · Cited by 52 · see citing works
Mohammed, O. S., Attia, H. G., Mohamed, B. M. S. A., Elbaset, M. A., & Fayed, H. M. (2023) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.3389/jpps.2023.11808 · Cited by 46 · see citing works
Histological assessment based on liver biopsy: the value and challenges in NASH drug development
Tong, X., Wang, Q., Zhao, X., Sun, Y., Wu, X., Yang, L., Lu, Z., Ou, X., Jia, J., & You, H. (2022) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-00874-x · Cited by 44 · see citing works
The clinical anti-inflammatory effects and underlying mechanisms of silymarin
Zhao, Y., Zhou, Y., Gong, T., Liu, Z., Yang, W., Xiong, Y., Xiao, D., Cifuentes, A., Ibáñez, E., & Lu, W. (2024) · iScience · doi:10.1016/j.isci.2024.111109 · Cited by 39 · see citing works
Diagnostic and therapeutic strategies for non-alcoholic fatty liver disease
Fu, Y., Zhou, Y., Shen, L., Li, X., Zhang, H., Cui, Y., Zhang, K., Li, W., Chen, W., Zhao, S., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.973366 · Cited by 36 · see citing works
Jin, Y., Wang, X., Chen, K., Chen, Y., Zhou, L., Zeng, Y., Zhou, Y., Pan, Z., Wang, D., Li, Z., et al. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02220-y · Cited by 34 · see citing works
Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD
Vitulo, M., Gnodi, E., Rosini, G., Meneveri, R., Giovannoni, R., & Barisani, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612748 · Cited by 33 · see citing works
Authors, & Collaborators: (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1880-2388 · Cited by 30 · see citing works
Hashem, A., Shastri, Y., Otaibi, M. A., Buchel, E., Saleh, H., Ahmad, R., Ahmed, H., Idris, F. A., Ahmed, S., Guda, M. F., et al. (2021) · Gastroenterology Insights · doi:10.3390/gastroent12020014 · Cited by 30 · see citing works
Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases
Lee, H. A., Chang, Y. W., Sung, P. S., Yoon, E. L., Lee, H. W., Yoo, J., Lee, Y., An, J., Song, D. S., Cho, Y. Y., et al. (2022) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2022.0186 · Cited by 30 · see citing works
Impact of Silymarin Supplements on Liver Enzyme Levels: A Systematic Review
Martinez, E. C., Herrera, D. A., Mogan, S., Hameed, Z. A., Jangda, A. A., Khan, T. J., Mroke, P., Sajid, S., Shah, Y. R., & Baig, I. (2023) · Cureus · doi:10.7759/cureus.47608 · Cited by 29 · see citing works
Misra, A., Kumar, A., Kuchay, M. S., Ghosh, A., Gulati, S., Choudhary, N. S., Dutta, D., Sharma, P., Vikram, N. K., Rastogi, A., et al. (2025) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2025.103209 · Cited by 27 · see citing works
Fibrosis progression rate in a systematic review of placebo‐treated nonalcoholic steatohepatitis
Roskilly, A., Hicks, A., Taylor, E., Jones, R. L., Parker, R., & Rowe, I. A. C. (2020) · Liver International · doi:10.1111/liv.14749 · Cited by 27 · see citing works
Present and Future Perspectives in the Treatment of Liver Fibrosis
Cerrito, L., Galasso, L., Iaccarino, J., Pizzi, A., Termite, F., Esposto, G., Borriello, R., Ainora, M. E., Gasbarrini, A., & Zocco, M. A. (2025) · Pharmaceuticals · doi:10.3390/ph18091321 · Cited by 27 · see citing works
Huang, Q., An, Z., Xin, X., Gou, X., Tian, X., Hu, Y., Mei, Z., & Feng, Q. (2024) · Food Science & Nutrition · doi:10.1002/fsn3.4595 · Cited by 25 · see citing works
The Effect of Bioactive Aliment Compounds and Micronutrients on Non-Alcoholic Fatty Liver Disease
Munteanu, C., & Schwartz, B. (2023) · Antioxidants · doi:10.3390/antiox12040903 · Cited by 24 · see citing works
Savari, F., & Mard, S. A. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e28468 · Cited by 21 · see citing works
Seidita, A., Cusimano, A., Giuliano, A., Meli, M., Carroccio, A., Soresi, M., & Giannitrapani, L. (2024) · Antioxidants · doi:10.3390/antiox13060731 · Cited by 21 · see citing works
Amorim, R., Soares, P., Chavarria, D., Benfeito, S., Cagide, F., Teixeira, J., Oliveira, P. J., & Borges, F. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116723 · Cited by 21 · see citing works
Cho, J.-H., Lee, J.-S., Kim, H.-G., Lee, H. W., Fang, Z., Kwon, H. H., Kim, D. W., Lee, C., & Jeong, J.-W. (2021) · Antioxidants · doi:10.3390/antiox10070998 · Cited by 21 · see citing works
Therapeutic Targets and Approaches to Manage Inflammation of NAFLD
Geng, W., Liao, W., Cao, X., & Yang, Y. (2025) · Biomedicines · doi:10.3390/biomedicines13020393 · Cited by 20 · see citing works
Lamooki, F. M., Alami, F., Toupchi, F. M., Jalali, P., Banimahdidehkordi, A., Baziyar, P., Ghiabi, S., Heidari-Soureshjani, E., & Mirahmadi, S. A. (2025) · Results in Chemistry · doi:10.1016/j.rechem.2025.102484 · Cited by 19 · see citing works
Bahari, H., Jazinaki, M. S., Rashidmayvan, M., Taheri, S., Amini, M. R., & Malekahmadi, M. (2024) · Inflammopharmacology · doi:10.1007/s10787-023-01423-6 · Cited by 18 · see citing works
Hepatocellular Interactions of Potential Nutraceuticals in the Management of Inflammatory NAFLD
Ezhilarasan, D., & Kulanthaivel, L. (2024) · Cell Biochemistry and Function · doi:10.1002/cbf.4112 · Cited by 17 · see citing works
Sokal-Dembowska, A., Jarmakiewicz-Czaja, S., & Filip, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252011187 · Cited by 16 · see citing works
Silymarin for Treating Toxic Liver Disease: International Consensus Recommendations
Gillessen, A., Angelico, F., Chen, J., Lu, L., Lucena, M. I., Fu, Q., Xie, Q., Andrade, R. J., Xie, W., Xu, X., et al. (2022) · Gastro Hep Advances · doi:10.1016/j.gastha.2022.05.006 · Cited by 16 · see citing works
Su, Y., Kang, Y., Yi, J., Lin, Q., Zhang, C., Lin, Z., Yan, Z., Qu, J., & Liu, J. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/2122563 · Cited by 15 · see citing works
Malik, A., Malik, M., & Qureshi, S. (2024) · Canadian Liver Journal · doi:10.3138/canlivj-2023-0021 · Cited by 15 · see citing works
Wang, Y., He, Y., Sun, W., Yu, H., Tao, W., Yu, X., Jia, D., Liu, Y., Pandol, S. J., & Li, L. (2024) · Drugs · doi:10.1007/s40265-024-02015-6 · Cited by 15 · see citing works
Khawaja, G., & El-Orfali, Y. (2024) · Pharmaceuticals · doi:10.3390/ph17040431 · Cited by 15 · see citing works
Li, Y., Lei, R., Lei, H., Qin, X., Xie, F., Yao, C., & Feng, P. (2022) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000002471 · Cited by 15 · see citing works
Huang, H., Qin, J., Wen, Z., Liu, Y., Chen, C., Wang, C., Li, H., & Yang, X. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155598 · Cited by 14 · see citing works
Navarro, V. J., Belle, S. H., D’Amato, M., Afdhal, N. H., Brunt, E. M., Fried, M. W., Reddy, K. R., Wahed, A. S., Harrison, S. A., & on behalf of the Silymarin in NASH and C Hepatitis (SyNCH) Study Group (2019) · PLoS ONE · doi:10.1371/journal.pone.0223915 · Cited by 14 · see citing works
Self-citationMohammed, S., Hassany, M., Eysa, B. E., Adel, A., Zidan, A., & Mohamed, S. (2025) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-024-04692-y · Cited by 13 · see citing works
Taghipour, A., Ghaffarifar, F., Horton, J. D., Dalimi, A., & Sharifi, Z. (2021) · Tropical Medicine and Health · doi:10.1186/s41182-021-00363-7 · Cited by 13 · see citing works
da Silva, C. M., Ferrari, G. D., Alberici, L. C., Malaspina, O., & Moraes, K. C. M. (2020) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-020-03717-7 · Cited by 13 · see citing works
Handu, D., Stote, K. S., & Piemonte, T. A. (2025) · Nutrients · doi:10.3390/nu17030453 · Cited by 12 · see citing works
Wang, J., Zhang, L., Cao, H., Shi, X., Zhang, X., Gao, Z., Ikeda, K., Yan, T., Jia, Y., & Xu, F. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154022 · Cited by 12 · see citing works
Tay, P. W. L., Ng, C. H., Lin, S. Y., Chin, Y. H., Xiao, J., Lim, W. H., Lim, S. Y., Fu, C. E., Chan, K. E., Quek, J., et al. (2022) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000002042 · Cited by 12 · see citing works
Silymarin: A Natural Compound for Obesity Management
de Freitas, J. A., Santamarina, A. B., Otoch, J. P., & Pessoa, A. F. M. (2024) · Obesities · doi:10.3390/obesities4030024 · Cited by 11 · see citing works
Synthesis and Anti-Liver Fibrosis Research of Aspartic Acid Derivatives
Lv, M., Guo, S., Hexian, Y., Wang, Y., Li, Y., Li, Y., Yi, H., He, H., & Li, Z. (2024) · Molecules · doi:10.3390/molecules29194774 · Cited by 11 · see citing works
Phenotypic screen identifies the natural product silymarin as a novel anti-inflammatory analgesic
DuBreuil, D. M., Lai, X., Zhu, K., Chahyadinata, G., Perner, C., Chiang, B. M., Battenberg, A., Sokol, C. L., & Wainger, B. J. (2022) · Molecular Pain · doi:10.1177/17448069221148351 · Cited by 11 · see citing works
Zhou, J., Chen, Y., Yu, J., Li, T., Lu, Z., Chen, Y., Zhang, X., & Ye, F. (2021) · Medicine · doi:10.1097/md.0000000000024884 · Cited by 11 · see citing works
Natural Products in the Modulation of Farnesoid X Receptor Against Nonalcoholic Fatty Liver Disease
Wang, J., Yang, N., & Xu, Y. (2024) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x24500137 · Cited by 10 · see citing works
Zhi, Y., Dong, Y., Li, X., Zhong, W., Lei, X., Tang, J. T., & Mao, Y. (2024) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3846 · Cited by 9 · see citing works
Molecular Pathways Governing the Termination of Liver Regeneration
de Haan, L. R., van Golen, R. F., & Heger, M. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.123.000955 · Cited by 9 · see citing works
Shi, R., Chai, K., Wang, H., Zhou, J., Yang, S., Li, J., Qiao, C., Sheng, X., Zhang, X., & Wu, J. (2025) · Journal of Evidence-Based Medicine · doi:10.1111/jebm.70002 · Cited by 9 · see citing works
Ghareeb, M. A., Hussein, T. M., Ibrahim, A. M., Abdel-Tawab, H., & Hammam, O. A. (2021) · Egyptian Journal of Chemistry · doi:10.21608/ejchem.2021.84043.4114 · Cited by 8 · see citing works
Clinical Management of COVID-19 in Cancer Patients with the STAT3 Inhibitor Silibinin
Bosch‐Barrera, J., Roqué, A., Teixidor, E., Carmona-Garcia, M. C., Arbusà, A., Brunet, J., Martı́n-Castillo, B., Cuyàs, E., Verdura, S., & Menéndez, J. A. (2021) · Pharmaceuticals · doi:10.3390/ph15010019 · Cited by 7 · see citing works
Kołota, A., & Głąbska, D. (2021) · Applied Sciences · doi:10.3390/app11135836 · Cited by 7 · see citing works
Yang, B., Yang, X., Tan, X., Lu, L., Fan, W., Barbier‐Torres, L., Steggerda, J. A., Liu, T., & Yang, H. (2022) · Canadian Journal of Gastroenterology and Hepatology · doi:10.1155/2022/6799414 · Cited by 7 · see citing works
Current Treatment Options, Including Diet, Exercise, and Medications
Noureddin, M., & Abdelmalek, M. F. (2023) · Clinics in Liver Disease · doi:10.1016/j.cld.2023.01.008 · Cited by 6 · see citing works
de Souza, M. H. G., Amaral, M. J. M., Lima, L. C. V., & Villela‐Nogueira, C. A. (2025) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.18498 · Cited by 6 · see citing works
Singh, A., & Ilango, K. (2022) · Journal of Applied Pharmaceutical Science · doi:10.7324/japs.2022.120605 · Cited by 6 · see citing works
Lee, Y. Y., & Tee, V. (2023) · Drugs in Context · doi:10.7573/dic.2023-2-10 · Cited by 6 · see citing works
Silymarin and management of liver function in nonalcoholic steatohepatitis: a case report
Hashem, A. (2023) · Drugs in Context · doi:10.7573/dic.2023-2-9 · Cited by 6 · see citing works
Lee, Y. Y., & Tee, V. (2023) · Drugs in Context · doi:10.7573/dic.2023-1-3 · Cited by 5 · see citing works
Herbal Medicines for the Treatment of Nonalcoholic Steatohepatitis
Sandhu, N., & Au, J. S. (2021) · Current Hepatology Reports · doi:10.1007/s11901-020-00558-2 · Cited by 5 · see citing works
Amjad, M. Z., Hassan, M. U., Rehman, M., Shamim, A., Zeeshan, H. M., Iftikhar, Z., Ahmed, A., & Jamil, M. I. (2024) · Cureus · doi:10.7759/cureus.76313 · Cited by 4 · see citing works
Silymarin for adults with metabolic dysfunction-associated steatotic liver disease
Wang, C., Shang, Y., Kanaan, G., Chai, L., Li, H., & Qi, X. (2025) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd015524.pub2 · Cited by 4 · see citing works
Andani, F. M., Talebi-Garakani, E., Nasiri, K., & Akbari, A. (2025) · Scientific Reports · doi:10.1038/s41598-025-20512-w · Cited by 4 · see citing works
Silymarin in the management of liver enzyme activity in steatohepatitis: a case report
Torre, A. (2023) · Drugs in Context · doi:10.7573/dic.2023-1-5 · Cited by 4 · see citing works
The pharmacological effects and therapeutic potential of flavonoids in digestive diseases
Xu, J., Zhang, J. C., Yu, B., Liu, C., & Zhang, L. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1684377 · Cited by 3 · see citing works
Silymarin for treatment of adults with nonalcoholic fatty liver disease
Wang, C., Kanaan, G., Shang, Y., Chai, L., Li, H., & Qi, X. (2023) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd015524 · Cited by 3 · see citing works
Milk Thistle (Silybum marianum)
Bokelmann, J. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-84676-9.00061-1 · Cited by 3 · see citing works
Micheli, L., Pacini, A., Mannelli, L. D. C., Trallori, E., D’Ambrosio, R., Bianchini, C., Lampertico, P., & Ghelardini, C. (2020) · Nutrients · doi:10.3390/nu12061819 · Cited by 3 · see citing works
Communicable and noncommunicable liver disease in HIV
Mauss, S., & Boesecke, C. (2021) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000675 · Cited by 3 · see citing works
Qin, L., Xiao, Q., & Deng, X. (2025) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s548513 · Cited by 2 · see citing works
Bhattacharya, J., Saifullah, Q., Dutta, K., Chakrabarty, S., Halder, A., Das, S., Khanra, R., Biswas, K., Sreeharsha, N., & Roy, P. (2026) · Discover Nano · doi:10.1186/s11671-026-04621-7 · Cited by 2 · see citing works
Dr. Gokula Krishnan, B., Sharma, D., Kumari, M., Arora, R., & Malik, D. K. S. (2026) · Cureus · doi:10.7759/cureus.110225 · Cited by 2 · see citing works
Rathnayake, D. W., Sooriyaarachchi, P., Niriella, M. A., Ediriweera, D. S., & Perera, J. A. (2024) · Advances in Integrative Medicine · doi:10.1016/j.aimed.2024.08.016 · Cited by 2 · see citing works
Liu, L., Li, Y., & Qi, X. (2022) · Nutrition · doi:10.1016/j.nut.2022.111648 · Cited by 2 · see citing works
Орлова, С. В., Vodolazkaya, A. N., Tarasova, O., Никитина, Е. А., Prokopenko, E. V., Balashova, N. V., Minosyan, I. S., & Urazov, V. V. (2024) · Medical alphabet · doi:10.33667/2078-5631-2024-16-13-18 · Cited by 2 · see citing works
Martínez, G., & Ángel, M. (2012) · Congreso de los Diputados eBooks · Cited by 2 · see citing works
Koutoukidis, D. A., Morris, E. M., Henry, J. A., Shammoon, Y., Zimmerman, M., Michalopoulou, M., Jebb, S. A., & Aveyard, P. N. (2021) · PLoS ONE · doi:10.1371/journal.pone.0250385 · Cited by 2 · see citing works
Lu, S., Jiang, Y., Ling, Y., Zhai, X., & Zhou, Y. (2025) · Bioscience Biotechnology and Biochemistry · doi:10.1093/bbb/zbaf064 · Cited by 1 · see citing works
- Authors
- Navarro, V. J., Belle, S. H., D’Amato, M., Adfhal, N., Brunt, E. M., Fried, M. W., Reddy, K. R., Wahed, A. S., Harrison, S., & on behalf of the Silymarin in NASH and C Hepatitis (SyNCH) Study Group
- Affiliations
- Jefferson Einstein Philadelphia Hospital (US)
- University of Pittsburgh (US)
- Beth Israel Deaconess Medical Center (US)
- Washington University in St. Louis (US)
- University of North Carolina at Chapel Hill (US)
- University of Pennsylvania (US)
- Brooke Army Medical Center (US)
- Corresponding author
- Navarro, Victor J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2019-09-19
- Volume
- 14
- Issue
- 9
- Pages
- e0221683
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC6752871
- OpenAlex
- W2973727343
- Cited by
- 125
- References
- 14
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 30 · 2023: 16 · 2022: 19 · 2021: 18 · 2020: 9 · 2019: 1 · 2012: 1
- FWCI
- 8.64
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-10-10)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- The Medicine Forum (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Rottapharm|Madaus
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Silymarin and Mushroom Poisoning
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Complementary and alternative medicine › Nigella sativa pharmacological applications
- Keywords
- silymarin, Silybum marianum, nonalcoholic steatohepatitis, non-cirrhotic liver disease, NAFLD activity score, liver fibrosis, antioxidant therapy, herbal supplement safety, dose comparison, histological improvement
- MeSH terms
- Adult, Antioxidants, Double-Blind Method, Female, Humans, Male, Middle Aged, Silymarin, Treatment Outcome, Intention to Treat Analysis, Non-alcoholic Fatty Liver Disease
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