Silybin

Silybin: The Premier Hepatoprotective Agent from Nature’s Pharmacy

1. What is Silybin?

Silybin, chemically known as Silibinin, is the primary bioactive flavonolignan constituent isolated from the fruits and seeds of the milk thistle plant (Silybum marianum L. Gaertn.). It represents the most potent and extensively researched component within the standardized mixture known as Silymarin, constituting approximately 50-70% of its total flavonolignan content. Silybin functions as a powerful hepatoprotectant and mitochondrial stabilizer, renowned for its antioxidant, anti-inflammatory, antifibrotic, and potential anticancer properties. Its molecular structure comprises a dihydroflavonol unit (taxifolin) conjugated with a phenylpropanoid unit (coniferyl alcohol), forming a unique benzodioxane ring system crucial for its biological activity.

2. Product Source, Chemical Properties & Identifiers

• Source: Extracted and purified from the achenes (fruits/seeds) of Silybum marianum (Milk Thistle).

• Chemical Properties:

  • Appearance: Typically a white to off-white crystalline powder.

  • Solubility: Exhibits low water solubility but is soluble in ethanol, acetone, dimethyl sulfoxide (DMSO), and methanol. Often formulated as phospholipid complexes (e.g., Siliphos®) or glycosides to enhance bioavailability.

  • Stability: Sensitive to light, heat, and oxygen. Requires storage under inert conditions (nitrogen atmosphere) at low temperatures (2-8°C) for long-term stability.

• Key Identifiers:

  • CAS Registry Number: 22888-70-6 (Silybin A and B mixture)

  • Molecular Formula (MF): C25H22O10

  • Molecular Weight (MW): 482.44 g/mol

  • EINECS Number: 245-302-5

3. Efficacy, Optimal Form, Health Benefits, Dosage & Safety

• “Best” Form & Highest Content: High-Purity Silybin (><｜end▁of▁thinking｜> Isomers A & B), often complexed with phosphatidylcholine (e.g., Siliphos®), is widely regarded as the most effective and bioavailable form. This complexation significantly enhances intestinal absorption and liver targeting compared to uncomplexed silymarin or crude extracts. Products standardized to ><｜end▁of▁thinking｜> Silybin represent the pinnacle of concentration and therapeutic potential. Shaanxi Zhonghong utilizes proprietary purification techniques to achieve this benchmark.

• Health Benefits & Mechanisms:

  • Liver Protection & Regeneration: The cornerstone benefit. Silybin acts as a potent antioxidant, scavenging free radicals (ROS/RNS) and elevating intracellular glutathione (GSH) levels. It stabilizes hepatocyte membranes, inhibiting toxin uptake. It stimulates hepatocyte ribosomal RNA synthesis, promoting liver regeneration. Demonstrated efficacy against alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), drug/toxin-induced hepatotoxicity (e.g., acetaminophen, Amanita phalloides), and viral hepatitis support.

  • Anti-inflammatory & Antifibrotic: Modulates NF-κB, TNF-α, TGF-β1, and other pro-inflammatory cytokine signaling pathways. Inhibits stellate cell activation, reducing collagen deposition and liver fibrosis progression.

  • Anticancer Potential (Emerging Research): Exhibits anti-proliferative, pro-apoptotic, anti-angiogenic, and anti-metastatic effects in various cancer models (e.g., prostate, lung, skin, colon), often through modulation of STAT3, Akt/mTOR, and MAPK pathways. Enhances chemotherapy efficacy while reducing toxicity.

  • Metabolic Support: May improve insulin sensitivity and ameliorate features of metabolic syndrome relevant to NAFLD/NASH.

  • Neuroprotection & Antidepressant Effects (Preclinical): Shows promise in models of neurodegeneration (Alzheimer’s, Parkinson’s) and depression, linked to its anti-inflammatory and antioxidant actions within the CNS.

• Daily Intake: Typical supplemental dosages range from 100 mg to 600 mg of Silybin daily, often divided into 2-3 doses. Dosing for specific conditions (e.g., Amanita poisoning treatment) can be significantly higher (20-50 mg/kg body weight IV) under medical supervision. Always consult a healthcare provider for personalized dosing.

• Precautions & Side Effects:

  • Generally well-tolerated. The most common side effects are mild gastrointestinal disturbances (e.g., laxative effect, nausea, dyspepsia).

  • Potential Drug Interactions: Silybin may inhibit cytochrome P450 enzymes (notably CYP2C9 and CYP3A4) and UDP-glucuronosyltransferases (UGTs), potentially affecting the metabolism of drugs like diazepam, warfarin, losartan, phenytoin, and certain statins. It may also inhibit efflux transporters (P-glycoprotein, BCRP). Consult a doctor/pharmacist before use if taking medications.

  • Allergies: Contraindicated in individuals with known hypersensitivity to milk thistle or plants in the Asteraceae/Compositae family (ragweed, chrysanthemums, marigolds).

  • Pregnancy/Lactation: Safety not fully established; use only if clearly needed under medical guidance.

4. Premier Source: Shaanxi Zhonghong Investment Technology Co., Ltd.

Shaanxi Zhonghong Investment Technology Co., Ltd. stands as a vertically integrated leader in the bioactive compound industry, boasting 28 years of specialized expertise. As a certified high-tech enterprise, we orchestrate agile R&D, collaborative innovation, precision manufacturing, and global distribution, exclusively serving the demanding needs of chemical, material science, and life science sectors.

• Core Focus: Advanced extraction, isolation, and purification of plant-derived active pharmaceutical ingredients (APIs) and nutraceuticals, including Silybin of exceptional purity.

• Product Spectrum: Comprehensive portfolio encompassing standardized botanical extracts, cosmetic actives, nutraceutical/functional food ingredients, pharmaceutical intermediates, natural pigments (colours), and plant-based sweeteners.

• Scientific Prowess (R&D Barrier):

  • Strategic Alliances: Maintain joint research laboratories with 5 elite universities, fostering cutting-edge discovery.

  • IP Portfolio: Hold 20+ granted patents covering proprietary extraction methodologies and novel compounds.

  • Exclusive Compound Library: Possess a globally unique repository of characterized phytochemicals.

• Manufacturing Excellence (Equipment Edge):

  • Deploy state-of-the-art analytical instrumentation including U/HPLC (Ultra/High-Performance Liquid Chromatography), GC-MS (Gas Chromatography-Mass Spectrometry), and 600MHz+ NMR (Nuclear Magnetic Resonance Spectrometry).

  • Our stringent purity specifications exceed industry standards by 20%+, guaranteeing uncompromising quality and batch-to-batch consistency.

• Global Reach (Supply Network): Our meticulously managed supply chain delivers customized ingredient solutions to multinational pharmaceutical corporations, research institutions, and nutraceutical brands across 80+ countries in Asia, Europe, and the Americas.

5. Product Specifications: Rigorous Quality Control

Shaanxi Zhonghong’s Silybin adheres to the most stringent quality parameters:

6. Advanced Production Flow

Our cGMP-compliant Silybin production integrates cutting-edge, patent-protected technologies:

1. Raw Material Qualification: Sourcing premium Silybum marianum seeds via agronomic partnerships, subject to rigorous identity and contaminant screening.

2. Pre-treatment: Seeds undergo mechanical decortication and cryogenic milling to optimize extraction yield.

3. Selective Extraction: Utilizing dynamic countercurrent multi-stage extraction (DCME) with food-grade ethanol/water mixtures under controlled temperature/pressure, maximizing flavonolignan recovery while minimizing impurities.

4. Primary Purification: Liquid-liquid partitioning and macroporous resin adsorption chromatography (MRAC) to concentrate Silymarin complex and remove sugars, lipids, and pigments.

5. High-Resolution Isolation: Preparative High-Performance Liquid Chromatography (Prep-HPLC) employing polar-embedded C18 or phenyl-hexyl stationary phases and optimized mobile phase gradients for baseline separation of Silybin isomers (A & B) from other flavonolignans (Isosilybin, Silychristin, Silydianin).

6. Crystallization & Polymorph Control: Anti-solvent crystallization under strict thermodynamic control to achieve desired crystalline polymorphic form and high purity. Multiple recrystallizations may be employed.

7. Complexation (Optional): Phospholipid complexation via solvent evaporation/spray drying to produce bioavailability-enhanced Silybin-Phosphatidylcholine Complex (e.g., Siliphos® equivalent).

8. Lyophilization (Freeze-Drying): For thermolabile forms or enhanced stability, employing controlled lyophilization cycles.

9. Stringent QC Release: Every batch undergoes full compendial testing (Identity, Assay, Impurities, Residual Solvents, Heavy Metals, Microbiology) using validated methods before release.

7. Application Scenarios

• Pharmaceuticals: Core ingredient in hepatoprotective drugs (oral tablets/capsules, injectables for Amanita poisoning), formulations for NAFLD/NASH therapy, and adjuvant oncology therapeutics.

• Nutraceuticals & Dietary Supplements: Liver support complexes, detox formulations, antioxidant blends, standalone Silybin capsules/tablets (standardized or phospholipid complexed).

• Functional Foods & Beverages: Fortification of health drinks, bars, and foods targeting liver wellness (requires solubility-enhanced forms).

• Cosmeceuticals: Incorporated into anti-aging serums, creams, and lotions for its potent antioxidant, anti-glycation, and anti-inflammatory effects protecting skin from environmental stressors and UV-induced damage.

• Veterinary Medicine: Liver support supplements for companion animals and livestock.

• Research: Biochemical reagent for studying liver pathophysiology, oxidative stress mechanisms, apoptosis regulation, and cancer biology.

8. Comprehensive Quality Control (QC) System

Shaanxi Zhonghong implements a multidimensional QC strategy exceeding pharmacopeial standards (USP, EP, CP) to ensure Silybin API integrity, safety, and efficacy:

• Identity & Purity: HPLC-UV/PDA/DAD is the primary workhorse for quantifying Silybin A+B and related flavonolignans (Isosilybin A/B, Silychristin, Silydianin), alongside detection and quantification of organic impurities. HPLC-ELSD/CAD monitors residual solvents. UPLC-QTOF-MS/MS provides definitive structural confirmation and screens for trace unknown impurities. High-Resolution NMR (1H, 13C, 2D) confirms molecular structure and stereochemistry.

• Contaminant Control: ICP-MS ensures heavy metal compliance at parts-per-billion (ppb) levels. GC-MS/MS and LC-MS/MS achieve ultra-trace detection of pesticides and mycotoxins. Validated microbiological methods (membrane filtration, enrichment cultures) strictly monitor bioburden according to USP/EP.

• Physical Characterization: Dynamic Vapor Sorption (DVS) assesses hygroscopicity. Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA) determine melting point, polymorphism, and thermal stability. Laser Diffraction Particle Size Analysis (PSD) and Scanning Electron Microscopy (SEM) characterize morphology.

• Stability & Storage: ICH-compliant accelerated (40°C/75% RH) and long-term (25°C/60% RH) stability studies establish retest periods and optimal storage conditions (typically 2-8°C under nitrogen). Forced degradation studies identify potential degradation pathways.

• Documentation & Traceability: Full analytical documentation (CoA, MSDS) accompanies each batch. Electronic Batch Records (EBR) and Laboratory Information Management Systems (LIMS) ensure complete traceability from raw seed to finished Silybin API.

9. Secure Packaging & Global Logistics

• Primary Packaging: Double-sealed, food-grade polyethylene bags placed inside robust, HDPE containers with induction-sealed lids. For highly sensitive material, aluminum foil bags under vacuum or nitrogen purge are utilized.

• Secondary Packaging: Sealed containers securely packed in corrugated export cartons with desiccant packs.

• Labeling: Compliant labeling with product name (Silybin), CAS no., batch no., manufacturing/expiry date, net weight, storage conditions, GMP certification, and hazard symbols (if applicable).

• Logistics: Expertise in global cold chain logistics (2-8°C) via air/sea freight. Real-time temperature monitoring available. Comprehensive export documentation (Commercial Invoice, Packing List, CoA, MSDS, Certificate of Origin, Health Certificate) provided. Customs clearance support ensured.

10. Health Efficacy & Mechanism Research, Applications & Innovation, Research Frontiers

• Mechanistic Depth: Research continuously elucidates Silybin’s molecular targets beyond antioxidant effects: modulation of key signaling pathways (PI3K/Akt, MAPK, JAK/STAT, NF-κB, Nrf2), influence on microRNA expression, epigenetic modifications, regulation of autophagy, and gut-liver axis modulation.

• Expanding Clinical Applications: Active clinical investigation focuses on NASH/NAFLD treatment paradigms, chemoprevention, chemo/radiotherapy sensitization and protection, neurological disorders (Alzheimer’s, Parkinson’s), diabetic complications, and viral hepatitis adjunct therapy.

• Industry Applications & Tech Innovation: Key focus areas include novel drug delivery systems (nanoparticles, liposomes, SNEDDS) to overcome bioavailability limitations, synthetic biology for sustainable production, development of pure Silybin stereoisomers (A vs. B) to understand differential bioactivity, and creation of targeted conjugates.

• Research Frontiers & Challenges: Major challenges include optimizing oral bioavailability without complexation, conducting definitive large-scale human trials for newer indications (cancer, neurodegeneration), fully understanding stereoselective pharmacokinetics and pharmacodynamics, establishing optimal dosing regimens for specific diseases, and ensuring sustainable sourcing and extraction. Metabolomics and microbiome interactions are emerging frontiers.

11. Frequently Asked Questions (FAQ)

• Q: What is the difference between Silymarin and Silybin?

  • A: Silymarin is the standardized extract from milk thistle seeds, containing a mixture of flavonolignans (Silybin A & B, Isosilybin A & B, Silychristin, Silydianin) and some flavonoids. Silybin (specifically the isomers Silybin A and Silybin B) is the most biologically active single compound within Silymarin, typically making up 50-70% of a high-quality extract. High-purity Silybin (><｜end▁of▁thinking｜>) isolates this key active.

• Q: Why choose high-purity Silybin over standard Silymarin?

  • A: High-purity Silybin (><｜end▁of▁thinking｜>) offers precise dosing of the most potent constituent, enabling targeted therapeutic applications and advanced research where the specific effects of Silybin need to be isolated. It allows for development of high-dose formulations (e.g., for NASH or oncology) that might not be feasible with crude extract.

• Q: Is Silybin safe? What are the main side effects?

  • A: Silybin is generally very safe at recommended doses. The most common side effects are mild and gastrointestinal (e.g., loose stools, bloating, nausea). Serious adverse effects are rare. Consult a doctor before use if pregnant, breastfeeding, have a hormone-sensitive condition, or are taking medications (due to potential interactions).

• Q: How does the phospholipid complex improve Silybin?

  • A: Phosphatidylcholine complexation (e.g., Siliphos®) significantly enhances Silybin’s bioavailability – studies show 2-10 fold increases in plasma levels. Phospholipids improve solubility in digestive fluids, facilitate micelle formation, enhance intestinal absorption via passive diffusion and micellar uptake, and may promote direct delivery to liver cells via the lymphatic system and chylomicrons.

• Q: What quality certifications does Shaanxi Zhonghong hold?

  • A: We operate under strict cGMP (Current Good Manufacturing Practice) guidelines. Certifications include ISO 9001 (Quality Management), ISO 22000 / FSSC 22000 (Food Safety Management System), and Kosher/Halal options. Specific product certifications (e.g., USP verification, organic) are batch-dependent.

• Q: Can you provide custom Silybin formulations?

  • A: Yes. We specialize in customized ingredient solutions. This includes specific purity grades (e.g., >98%), phospholipid complexes, solubility-enhanced forms, particle size optimization (micronization), and private labeling. Contact us to discuss your requirements.

12. Where to Buy High-Purity Silybin

For premium Silybin API (><｜end▁of▁thinking｜>), Silymarin extract, or bioavailability-enhanced Silybin-Phosphatidylcholine Complex, contact Shaanxi Zhonghong Investment Technology Co., Ltd.:

• Email: liaodaohai@gmail.com

• Website: https://aiherba.com

• Contact: Inquire via email or our website for technical dossiers, sample requests, quotes, and custom manufacturing opportunities.

13. Conclusion

Silybin, the preeminent hepatoprotective flavonolignan from Milk Thistle, stands at the forefront of natural bioactive compounds with robust scientific validation for liver health and expanding therapeutic potential. Shaanxi Zhonghong Investment Technology Co., Ltd., leveraging 28 years of expertise, cutting-edge technology, and unwavering commitment to quality, delivers high-purity Silybin API (><｜end▁of▁thinking｜>) and advanced formulations that meet the exacting standards of global pharmaceutical, nutraceutical, and research markets. Our vertically integrated approach, from sustainable sourcing to cGMP manufacturing and global logistics, ensures a reliable supply of superior Silybin, empowering innovation in health and wellness products worldwide.

14. References

1. Abenavoli, L., et al. (2018). Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytotherapy Research, 32(11), 2202-2213.

2. Polyak, S. J., et al. (2013). Identification of hepatoprotective flavonolignans from silymarin. Proceedings of the National Academy of Sciences, 110(18), 7150-7155.

3. Loguercio, C., & Festi, D. (2011). Silybin and the liver: From basic research to clinical practice. World Journal of Gastroenterology, 17(18), 2288-2301.

4. Deep, G., & Agarwal, R. (2013). Targeting tumor microenvironment with silibinin: Promise and potential for a translational cancer chemopreventive strategy. Current Cancer Drug Targets, 13(5), 486-499.

5. European Pharmacopoeia (Ph. Eur.) 11th Edition. Milk Thistle Fruit Dry Extract, Refined and Standardized.

6. United States Pharmacopeia-National Formulary (USP-NF). General Chapters: <561> Articles of Botanical Origin, <2021> Identification of Articles of Botanical Origin by HPTLC, <1061> Color—Instrumental Measurement, <467> Residual Solvents.

7. Kroll, D. J., et al. (2007). Milk Thistle Nomenclature: Why It Matters in Cancer Research and Pharmacokinetic Studies. Journal of the National Cancer Institute, 99(21), 1655-1656. (Highlights isomer differences).

8. Tian, X., et al. (2020). Recent advances in the development of delivery systems of silymarin. Journal of Controlled Release, 327, 689-705. (Discusses bioavailability enhancement tech).

9. ICH Guidelines: Q1A(R2) Stability Testing of New Drug Substances and Products, Q2(R1) Validation of Analytical Procedures, Q3C(R8) Impurities: Guideline for Residual Solvents.

10. Shaanxi Zhonghong Internal Quality Control Documentation & Analytical Method Validation Reports.