Figure 1.
Silymarin: components, structure, multifunctional roles in aquaculture, and limitations
Table 1.
Milk thistle (Silybum marianum) applications on fish species performance
| Name | Product type and source | Tested dosage | Period | Route of administration | Fish species | Growth, feed utilization and survival | Biochemical variables | Immune-enhancing effects | Antioxidant effects | Gene expression | Challenges resistance | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Milk thistle (Silybum marianum) extract | Powder – purchased from Trade Company | 0, 0.1, 0.2, and 0.3% | 60 d | In diet | Striped catfish (Pangasianodon hypophthalmus) | WG, FI and SGR (↑), FCR, and SR (↔) | ALP, ALT, and AST (↓), urea, uric acid, and creatinine (↔) | LYZ and total Ig (↑) | SOD and CAT (↑), MDA (↓), GPx (↔) | ND | NM | (Abdel-Latif et al., 2023) |
| Silybum marianum extract | Powder – purchased from Trade Company | 0. 1, 2, 3, and 4 g/kg | 60 d | In diet | Nile tilapia (Oreochromis niloticus) | WG and SGR (↑), FCR and FI (↓), SR (↔) | ALP, ALT, and AST (↓), creatinine urea, albumin, globulin, and total protein (↔) | ND | MDA (↓), GPx, and T- AOC (↑), GST (↔) | IFN-γ1, LYZ, hepcidin, SOD, CAT, and GPx (↑) | NM | (Chaklader et al., 2024) |
| Silybum marianum seeds | Seeds; Egypt (Benha Univ., NIOF) | 0, 2.5, 5, 7.5, and 10 g/kg | 10 wks | In diet | Nile tilapia (Oreochromis niloticus) | SR, FBW, WG, SGR, PER, and APU (↑), FCR (↓), FI (↔) | AST and ALT (↓), total protein, globulin, and albumin (↑) | ND | T-AOC and CAT (↑), SOD (↑) | GH, IGM-2, SOD, and CAT (↑) | NM | (Hassaan et al., 2019) |
| Milk thistle (Silybum marianum) | Legalon Silymarin® 140 mg; Madaus GmbH, Köln, Germany. | 0, 200, 400, and 600 mg/kg | 60 d | In diet | European seabass (Dicentrarchus labrax) | FBW, ADG, SGR, SR, and PER (↑), FCR (↓) | ND | ND | TBARS and CAT (↑), SOD (↔) | ND | NM | (Shahin et al., 2023) |
| Silymarin extract (Silybum marianum) | Seed powder; silymarin extract per Banaee et al. (2011) | 0, 0.1, 0.4, and 0.8 g/kg | 30 d | In diet | Rainbow trout (Oncorhynchus mykiss) | ND | Total protein, globulin, and albumin (↑) | ACH50 and LYZ (↑) | ND | ND | NM | (Ahmadi et al., 2012) |
| Silymarin extract (SIE) | Powder – locally sourced, extracted per Hajirezaee et al. (2019) | 400, 1400, 2400 mg SIE/kg | 60 d | In diet | Common carp (Cyprinus carpio) | FBW, FWG, FCR, and SR (↔) | ALT, AST, ALP, CK, and LDH (↔) | ND | T-AOC, GPx, CAT, and SOD (↑), MDA and AChE (↔) | ND | Exposed to cadmium chloride | (Al-Shawi et al., 2022) |
| Dried plant and seed meal of Silybum marianum | Leaves, stems, and seeds from Univ. of Baghdad | 0%, 5%, 10%, 15%, 20% (plants); 5%, 10% (seeds) for T1–T7 respectively | 90 d | In diet | Common carp (Cyprinus carpio L.) | FBW, TWG, and SGR (↑) | ND | ND | ND | ND | NM | (Al-Jubouri and Al-Obaydi, 2021) |
| Milk thistle (Silybum marianum L.) | Capsules (140 mg), manufactured by Safe, Egypt; packed by SEDICO (Batch No. 0920468/2020). | 0.1% (1 g/kg) | 8 wks | In diet | Nile tilapia (Oreochromis niloticus) | SR (↑) | Total protein, albumin, and globulin (↑), ALT (↓), AST, ALP, TG, CH, HDL, and LDL (↔) | IL-1β, TNF-α, and IL-10 (↑)(↓) | GPx and CAT (↑)(↓) | ND | Oxytetracycline and Aeromonas hydrophila | (Sherif et al., 2023) |
| Milk thistle (Silybum marianum) | 70% silymarin from Zenith Nutrition, Medizen Labs, Bangalore, India. | 1 g/kg | 30 d | In diet | Common carp (Cyprinus carpio) | ND | ALT, AST, ALP (↓) | ND | ND | ND | Deltamethrin exposure | (Jindal et al., 2024) |
| Micelle silymarin | Synergen Inc. (Bucheon, South Korea). | Micelle silymarin: 0.025–0.4%; regular silymarin: 0.1 and 0.2% (M0025–M04, S01, S02). | 70 d | In diet | Olive flounder (Paralichthys olivaceus) | FBW, WG, and SGR (↑), FCR and SR (↔) | Glucose and total protein (↑), AST and ALT (↓) | LYZ, anti-protease, MPO, and TIg (↑) | SOD and GPx (↑), MDA (↓) | ND | NM | (Kim et al., 2023) |
| Milk thistle (Silybum marianum) | Purchased from Gol Drug Co., Iran | 0, 100, 400, and 800 mg/kg | 4 wks | In diet | Rainbow trout (Oncorhynchus mykiss) | ND | Total protein, albumin, and globulin (↑), glucose, cholesterol, triglyceride, AST, ALT, ALP, and creatinine (↓), uric acid and urea (↔) | ND | T-AOC (↑) | ND | NM | (Banaee et al., 2011) |
| Milk thistle (Silybum marianum) | (95%, Leader Bio-technology Co., Ltd., Guangzhou, China) | 0, 20, 40, 60, 80, and 100 mg/kg | 70 d | In diet | Grass carp (Ctenopharyngodon idella) | FBW, SGR, PWG, FI and FE (↑) | ND | ND | ND | ZO-1, occludin, JAM-A, claudin-b, −c, −f, −3c and – 11 (↑)(↓), claudin-7a, −7b, and 15b (↔), ZO-2b (↑)(↓)(↔). E- cadherin, α-catenin, β-catenin, nectin and afadin (↑)(↓), RhoA, MLCK and NMII (↓)(↑) | NM | (Wei et al., 2020) |
| Free and nanoencapsulated silymarin | Free silymarin (FS) from Sami Labs, India; nanoencapsulated silymarin (NS, Sinalive®) from Exir Nano Sina Co., Iran. | 50 and 200 mg/kg | 50 d | In diet | Nile tilapia (Oreochromis niloticus) | WG, FCR, and SGR (↔) | AST, ALT, LDH, and TP (↔) | ND | SOD and GPx (↑), MDA (↓) | ND | Silver nanoparticles (AgNPs) | (Veisi et al., 2021) |
| Milk thistle (Silybum marianum) | (95%, Leader Bio-technology Co., Ltd., Guangzhou, China) | 0, 20, 40, 60, 80, and 100 mg/kg | 70 d | In diet | Grass carp (Ctenopharyngodon idella) | ND | ND | LYZ, ACP, C4, and IgM (↑) | ND | Hepcidin, LEAP-2 A, – 2B, β-defensin-1, Mucin-2, TGF-β1, − β2, IL-4/13 A, and IL-10 (↑)(↓), JAK1, JAK2, STAT3b1, STAT3b2, and STAT6 (↑)(↓), TYK2 and STAT1 (↓)(↑), TNF-α, IL-12p40, IL-6, and IL-15 (↓)(↑), IL-1β, IL-12p35, and IL-17D (↔) | Aeromonas hydrophila | (Jia et al., 2025) |
[i] Variation in the treated crustaceans compared with controls: (↑), significantly increases; (↓), significantly decreased; (↔), no significant change.
[ii] Where, AChE: acetylcholinesterase, ACP: acid phosphatase, ADG: average daily gain, AFADIN: actin filament-associated protein, ALB: albumin, ALP: alkaline phosphatase, ALT: alanine aminotransferase, APU: apparent protein utilization, AST: aspartate aminotransferase, β-catenin: beta-catenin, β-defensin-1: beta defensin 1, CAT: catalase, C4: complement component 4, CH: cholesterol, CK: creatine kinase, Claudinb/c/f/3c/7a/7b/11/15b: claudin tight junction proteins (various isoforms), E-cadherin: epithelial cadherin, FE: feed efficiency, FBW: final body weight, FI: feed intake, FCR: feed conversion ratio, FWG: final weight gain, GH: growth hormone, GPx: glutathione peroxidase, GSH: glutathione, GST: glutathione S-transferase, HDL: high-density lipoprotein, IgM: immunoglobulin M, IGM-2: immunoglobulin heavy chain-2, IL-1β: interleukin-1 beta, IL-4/13 A: interleukin 4 and interleukin 13 isoform A, IL-6: interleukin 6, IL-10: interleukin 10, IL-12p35: interleukin 12 subunit p35, IL-12p40: interleukin 12 subunit p40, IL-15: interleukin 15, IL-17D: interleukin 17D, JAK1: Janus kinase 1, JAK2: Janus kinase 2, JAM-A: junctional adhesion molecule-A, LDH: lactate dehydrogenase, LEAP-2A: liver-expressed antimicrobial peptide 2A, LEAP-2B: liver-expressed antimicrobial peptide 2B, LYZ: lysozyme, MDA: malondialdehyde, MLCK: myosin light chain kinase, MPO: myeloperoxidase, Mucin-2: mucin-2, NECTIN: nectin cell adhesion molecule, NMII: non-muscle myosin II, PER: protein efficiency ratio, PWG: percentage weight gain, RhoA: Ras homolog family member A, SGR: specific growth rate, SOD: superoxide dismutase, SR: survival rate, STAT1: signal transducer and activator of transcription 1, STAT3b1: signal transducer and activator of transcription 3b1, STAT3b2: signal transducer and activator of transcription 3b2, STAT6: signal transducer and activator of transcription 6, T-AOC: total antioxidant capacity, TBARS: thiobarbituric acid reactive substances, TG: triglyceride, TIg: total immunoglobulin, TNF-α: tumor necrosis factor-alpha, TP: total protein, TWG: total weight gain, TYK2: tyrosine kinase 2, WG: weight gain, ZO-1: zonula occludens 1, ZO-2b: zonula occludens 2b.
Table 2.
Milk thistle (Silybum marianum) applications with other additions on fish species performance
| Name | Product type and source | Tested dosage | Other additions | Period | Route of admin istrati on | Fish species | Growth, feed utilization and survival | Biochemical variables | Immune-enhancing effects | Antioxidant effects | Gene expression | Challenges resistance | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Silybum marianum (SLM) | NM | 10 g SLM/kg | Co-enzyme Q10 (40 mg Co-Q10 mg/kg) | 40 d | In diet | Nile tilapia (Oreochromis niloticus) | FBW, BWG, DWG, SGR, and K (↑), SR (↔) | ALT, AST, ALP, urea, and creatinine (↓) | C3 and IgM (↑), LYZ (↔), | T-AOC (↑), MDA (↓), NO (↔) | TNF-α, IL-1B, CC, and CXC (↓), IL10 (↑), | Pseudomonas aeruginosa and Ni accumulation | (El-Houseiny et al., 2022 b) |
| Silybum marianum | Free Trade Egypt Co. (Alexandria, Egypt). | 1.0 and 2.0 g/kg | Ginkgo biloba, Moringa oleifera, Myristica fragrans, and Astragalus membranaceus | 56 d | In diet | Pangasianodon hypophthalmus | FBW, WG, and SGR (↑), FCR (↓), SR (↔) | TP, ALB, GLO, and A/G ratio (↑) | Total Ig, LYZ, C3, and BA (↑) | ND | ND | Acute ammonia stress | (Abdelaziz et al., 2023) |
| Milk thistle (Silybum marianum) | Legalon Silymarin® 140 mg; Madaus GmbH, Köln, Germany. | 250, 450, 650, 850, 1050 mg/kg | Selenium (Se, 0.5 mg/kg) | 60 d | In diet | Thinlip mullet (Lizaramada) | WG, ADG, SGR, and PER (↑), FCR (↓), SR (↔) | Total protein, albumin, and globulin (↑), glucose, total cholesterol, triglyceride, ALT, AST, and urea (↓), creatinine (↔) | LYZ, BA, NBT% and ACH50 (↑) | SOD, CAT, and GPx (↑) | IL-1β and hepcidin (↓) | NM | (Shehata et al., 2024 b) |
| Milk thistle (Silybum marianum) | Purchased from Swanson Health Products (SHP), Fargo, ND, USA. | 1 g/kg | Berberine (100 and 200 mg/kg feed) | 9 wks | In diet | Common carp (Cyprinus carpio) | FW and SGR (↑), FCR (↓) | TG, CHOL, and LDL (↓), HDL (↑), AST, ALP, and GGT (↔) | LYZ (↑) | T-AOC and MDA (↔) | ND | Acetaminophen (APAP) | (Grădinariu et al., 2024) |
| Milk thistle (Silybum marianum) | Milk thistle seeds from Goldaru Pharmaceutic al Co. farm, Isfahan, Iran. | 400 mg/kg | Diazinon exposed (0.1 mg/L) | 21 d | In diet | Rainbow trout (Oncorhynchus mykiss) | ND | Total protein, albumin, and globulins (↑), AST, LDL, ALP, glucose, triglycerides, cholesterol, creatinine, urea, uric acid, and ammonia (↓) | ND | T-AOC, SOD and CAT (↑), GPx and MDA (↔) | ND | NM | (Banaee et al., 2023) |
| Milk thistle (Silybum marianum) | NM | 0 and 1 g/kg | Nickel oxide nanoparticles (NiO-NPs, 0, 100 and 500 mg/kg) | 60 d | In diet | Rainbow trout (Oncorhynchus mykiss) | ND | Alkaline protease (↑)(↓) | ND | ND | ND | NM | (Nazdar et al., 2018) |
| Milk thistle (Silybum marianum) | NM | 10 g/kg | Co-enzyme Q10 (CQ10, 40 mg/kg) | 60 d | In diet | African catfish (Clarias gariepinus) | FBW, BWG, DWG, and SGR (↑), | Total protein, albumin, and globulins (↑), AST, ALT, and ALP, urea and creatinine (↓) | LYZ and C3 (↑) | SOD, CAT, and GPX (↑), MDA (↔) | ND | Aeromonas sobria | (El-Houseiny et al., 2022 a) |
| Milk thistle (Silybum marianum) | Provided by Beijing Sunpu Biochem. Tech.Co., Ltd. (Beijing, China) | 0, 100, or 200 mg/kg | 4 or 8 % lipid level (low lipid, LL, and high lipid, HL, respectively) | 82 d | In diet | Grass carp (Ctenopharyngodon idella) | WG, SGR, and PER (↑), FCR (↓) | T-cholesterol LDLc, and Tbil (↓) | ND | SOD (↔), MDA (↓) | FAS and ACC (↔), HSL (↑), CPT1 (↓), HMGCR and CYP7A1 (↑), ATGL (↔) | NM | (Xiao et al., 2017) |
| Milk thistle (Silybum marianum) | NM | 10 g/kg | Co-enzyme Q10 (CQ10, 40 mg/kg) | 40 d | In diet | Nile tilapia (Oreochromis niloticus) | ND | ND | AChE (↑) | SOD, CAT, GPx, GSH, and GST (↑), MDA (↓) | ND | Nickel water pollution (Ni) | (Khalil et al., 2022) |
| Milk thistle (Silybum marianum, S) | Legalon Silymarin® 140 mg; Madaus GmbH, Köln, Germany | 850 mg/kg | L-carnitine (LC, 500 mg/kg) | 84 d | In diet | Nile tilapia (Oreochromis niloticus) | WG, ADG, SGR, and PER (↑), FCR (↓), SR (↔) | Total protein, albumin, and globulin (↑), glucose, total cholesterol, triglyceride, ALT, AST, and urea (↓), creatinine (↔) | LYZ, BA, NBT%, and IgM (↑), MDA (↓) | SOD, CAT, and GPx (↑) | IGF-1, IFNA-1, SOD, CAT, and Gsr (↑) | NM | (Shehata et al., 2025 b) |
[i] Variation in the treated crustaceans compared with controls: (↑), significantly increases; (↓), significantly decreased; (↔), no significant change.
[ii] Where, A/G ratio: albumin/globulin ratio, AChE: acetylcholinesterase, ACC: acetyl-CoA carboxylase, ACH50: alternative complement hemolytic activity 50, ADG: average daily gain, ALB: albumin, ALP: alkaline phosphatase, ALT: alanine aminotransferase, AST: aspartate aminotransferase, ATGL: adipose triglyceride lipase, BA: bactericidal activity, BWG: body weight gain, C3: complement component 3, CAT: catalase, CHOL: cholesterol, CPT1: carnitine palmitoyltransferase I, CXC: CXC chemokines (a chemokine subfamily), CYP7A1: cholesterol 7 alpha-hydroxylase, DWG: daily weight gain, FAS: fatty acid synthase, FBW: final body weight, FCR: feed conversion ratio, FW: final weight, GGT: gamma-glutamyl transferase, GH: growth hormone (previously defined), GLO: globulin, GPx: glutathione peroxidase, GSH: glutathione, GST: glutathione S-transferase, Gsr: glutathione reductase, HDL: high-density lipoprotein, HMGCR: 3-hydroxy-3-methylglutaryl-CoA Reductase, HSL: hormone-sensitive lipase, IgM: immunoglobulin M, IL-1β/IL-1B: interleukin 1 beta, IL-10: interleukin 10, LDL / LDLc: low-density lipoprotein (cholesterol), LYZ: lysozyme, MDA: malondialdehyde, NBT%: nitroblue tetrazolium reduction percentage, NO: nitric oxide, PER: protein efficiency ratio, SOD: superoxide dismutase, SR: survival rate, SGR: specific growth rate, TG: triglycerides, T-AOC: total antioxidant capacity, Tbil: total bilirubin, TNF-α: tumor necrosis factor-alpha, Total Ig: total immunoglobulin, TP: total protein, WG: weight gain.
Table 3.
Milk thistle (Silybum marianum) applications on crustacean species performance
| Name | Product type and source | Tested dosage | Period | Route of administration | Crustacean species | Growth, feed utilization and survival | Biochemical variables | Immune-enhancing effects | Antioxidant effects | Gene expression | Challenges resistance | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Silymarin and micelle silymarin (MS) | Silymarin and MS from Synergen, Bucheon, Korea. | MS: 0.25–4.0 g/kg; Silymarin: 1.0 and 2.0 g/kg in basal diet (Con, M0.25– M4, S1, S2). | 42 d | In diet | Pacific white shrimp (Litopenaeus vannamei) | FBW, SGR, and WG (↑), FCR (↓), SR (↔) | Total protein (↑), AST and ALT (↓), Glucose (↔) | LYZ and PO (↑) | SOD and GPx (↑), MDA (↓) | proPO and TLR-3 (↑), TNF-α (↓), TGF-β (↔) | Vibrio parahaemolyticus | (Hasanthi et al., 2024) |
[i] Variation in the treated crustaceans compared with controls: (↑), significantly increases; (↓), significantly decreased; (↔), no significant change.
[ii] Where, ALT: alanine aminotransferase, AST: aspartate aminotransferase, FBW: final body weight, FCR: feed conversion ratio, Glucose: blood glucose, GPx: glutathione peroxidase, LYZ: lysozyme, MDA: malondialdehyde, PO: peroxidase activity, proPO: prophenoloxidase, SGR: specific growth rate, SOD: superoxide dismutase, SR: survival rate, TGF-β: transforming growth factor-beta, TLR-3: toll-like receptor 3, TNF-α: tumor necrosis factor-alpha, total protein: serum total protein, WG: weight gain.