98% High-Purity Luteolin Food-Grade Flavonoid Extract: A Natural Plant-Derived "Multifunctional Health Factor"—From Molecular Mechanisms to Precision Application in Dietary Supplements
Luteolin, a flavonoid compound found in natural plants such as chrysanthemum, honeysuckle, and celery, has evolved from a traditional medicinal ingredient to a "star ingredient" in the dietary supplement market thanks to its unique multi-target bioactivities (antioxidant, anti-inflammatory, and immunomodulatory). This food-grade, 98% high-purity luteolin, purified through the synergistic combination of supercritical extraction and molecular distillation, achieves breakthroughs in both safety and bioavailability while preserving its natural activity. It is establishing a new paradigm in precision nutrition for niche areas such as immune health, metabolic regulation, and neuroprotection. The following provides an in-depth analysis of the technical core and market value of this natural flavonoid extract from perspectives including its molecular mechanism, production process, functional properties, application scenarios, and industry trends. I. Molecular Mechanism: "Multi-Dimensional Regulation" from Structural Properties to Biological Activity
The core value of luteolin stems from its C6-C3-C6 flavonoid core structure and the presence of hydroxyl groups at specific positions (3', 4', 5', and 7). This structure imparts its potent physiological activity:

Antioxidant Network Construction:
The multiple hydroxyl groups in the molecule scavenge reactive oxygen species (ROS), such as hydroxyl radicals (・OH) and superoxide anions (O₂⁻), through hydrogen atom transfer (HAT) mechanisms. Its ORAC value reaches 18,200 μmol TE/g, eight times that of vitamin C. It also activates the Nrf2/HO-1 pathway, upregulating the activity of endogenous antioxidant enzymes (SOD and GSH-Px), and reducing lipid peroxidation products (MDA) by 45% in cell-based experiments. Blocking Anti-Inflammatory Signaling Pathways:
By inhibiting NF-κB nuclear translocation (reducing p65 protein phosphorylation), it significantly reduces the secretion of pro-inflammatory factors (IL-6, TNF-α). In a lipopolysaccharide (LPS)-induced inflammation model, IL-6 levels were reduced by 62%. It also modulates the MAPK pathway (inhibiting p38 and JNK phosphorylation), blocking the inflammatory cascade, with an effect superior to that of common flavonoids (such as quercetin).
Metabolism and Immune Regulation:
Activating the AMPK pathway promotes glucose uptake (increasing GLUT4 translocation by 38%), reducing fasting blood glucose by 22% in an insulin resistance model. It also enhances Treg cell activity (upregulating Foxp3 expression by 50%), balancing the immune response and reducing autoimmune damage. II. Production Process: "Full-Chain Quality Control" from Plant Extraction to High-Purity Purification
The production of food-grade 98% luteolin requires balancing the preservation of natural activity with food safety. The core process focuses on three key steps: "Efficient Extraction - Precision Purification - Stabilization":
1. Green Extraction Technology: The "First Line of Defense" for Activity Preservation
Supercritical CO₂ Extraction:
Using dried chrysanthemum (luteolin content 0.8-1.2%) as the raw material, dynamic extraction is performed at a pressure of 25 MPa, a temperature of 45°C, and a CO₂ flow rate of 2.0 L/h. The yield reaches 0.75%, a 78% increase compared to the ethanol reflux method (0.42%). Low temperature (≤50°C) operation prevents degradation of heat-sensitive components, resulting in an initial luteolin purity of 35% and activity retention exceeding 95%. Enzyme-Assisted Extraction:
Cellulase (1.5%) is used to pretreat the plant material, disrupting the cell wall structure. This reduces extraction time from 4 hours to 1.5 hours and reduces solvent usage by 30%, meeting green production standards (residual solvent ≤ 10 ppm).
2. High-Precision Purification Process: The "Key Technology" for Purity Breakthrough
Molecular Distillation-Preparative Liquid Chromatography:
The crude extract was subjected to molecular distillation (vacuum 0.1 Pa, temperature 80°C) to remove fat-soluble impurities. It was then purified by preparative HPLC (mobile phase: methanol - 0.1% phosphoric acid in water = 55:45, flow rate 15 mL/min). The target peak achieved a purity of 98.6% and a single impurity content of ≤ 0.5%, meeting the standards of international pharmacopoeias such as USP and EP. Membrane Separation Technology:
A ceramic membrane with a molecular weight cutoff of 300 Da is used for filtration to remove large polysaccharides and proteins, increasing purification efficiency by 40% while reducing energy consumption by 25%, making it suitable for large-scale production.
3. Food-Grade Compliance Control: A "Double Guarantee" of Safety
Impurity Control:
Heavy metals (lead ≤ 0.1 mg/kg, arsenic ≤ 0.05 mg/kg) are tested by ICP-MS, and pesticide residues (such as BHC and DDT) are tested by GC-MS/MS. The limits comply with GB 2762-2022 and EU EC 1881/2006.
Microbiological Control:
Sterilization is performed using irradiation (dose 5-10 kGy) or moist heat sterilization (121°C/30 min), ensuring a total colony count ≤ 10³ CFU/g, mold and yeast ≤ 10² CFU/g, and no pathogens are detected. III. Functional Properties: "Performance Advantages" from Basic Health to Targeted Intervention
Compared to common flavonoid extracts (purity 50-80%), 98% luteolin achieves a qualitative leap in the following dimensions:

Improved Bioavailability:
After inclusion in cyclodextrin (72% inclusion rate), luteolin's oral bioavailability increased from 8.5% to 23.2%, peak plasma concentration (Cmax) reaching 125 ng/mL, and half-life (t½) extended to 6.8 hours, resolving the pain point of natural flavonoids: "high activity but poor absorption."

Enhanced Targeting:
The nanocomplex (180 nm particle size) formed with lactoferrin (LF) specifically binds to LF receptors on intestinal epithelial cells, increasing intestinal absorption by 3.2-fold while reducing first-pass metabolism in the liver (reducing metabolic losses by 40%). Functional Synergy:
It synergizes with vitamin C (1:1 ratio) for antioxidant activity, increasing ORAC from 18,200 to 29,500 μmol TE/g. It also synergizes with curcumin (3:1 ratio) for anti-inflammatory effects, increasing TNF-α inhibition from 58% to 79%, making it suitable for complex health needs.

IV. Application Scenarios: "Precision Functional Carrier" in Dietary Supplements
98% Luteolin, with its well-defined functional targets, has become a core ingredient in dietary supplements, with applications focused on four key health areas:
1. Immune Modulation Supplement: Enhances defense and balanced response
Formulation Design:
Luteolin (200 mg/day) + Zinc (15 mg/day) + Vitamin D (1000 IU/day) can reduce infection rates by 38% and shorten symptom duration by 2.5 days during peak seasonal influenza seasons, making it suitable for individuals with compromised immune systems. Dosage Form:
Hard capsules (filling capacity 300 mg/capsule) using HPMC hollow capsules to avoid gelatin cross-linking issues. Disintegration time ≤15 minutes, meeting the requirements of the 2025 edition of the Chinese Pharmacopoeia.
2. Metabolic Health Supplement: Modulating Glucose and Lipids and Weight Management
Clinical Support:
After 8 weeks, daily intake of 400 mg of luteolin reduced waist circumference by 2.8 cm, triglyceride levels by 19%, and insulin resistance index (HOMA-IR) by 23%, with no adverse reactions (safety assessment showed LD50 > 5 g/kg bw).
Application:
Microencapsulated powder (particle size 500 μm) can be directly compressed or mixed into meal replacement powders, masking bitterness (bitterness threshold increased from 0.03% to 0.15%) and significantly improving palatability. 3. Neuroprotective Supplement: Anti-Inflammation and Cognitive Support
Mechanism of Action:
Luteolin can penetrate the blood-brain barrier, inhibit microglial overactivation (reducing iNOS expression by 55%), reduce neuroinflammation, and shorten Morris water maze escape latency by 40% in an elderly cognitive decline model.
Product Formulation:
Oil suspension softgels (each containing 150 mg of luteolin) use medium-chain triglycerides (MCTs) as a carrier to promote absorption of fat-soluble components, resulting in a two-fold increase in bioavailability compared to the powder formulation.
4. Skin Health Supplement: Antioxidant and Photodamage Protection
Synergistic Formula:
Luteolin (300 mg/day) + astaxanthin (4 mg/day) can reduce ultraviolet (UVB)-induced skin erythema index (by 35%) and increase skin hydration (by 18%), making it suitable for photoaging prevention. V. Market Landscape: "Industrial Upgrading" from Raw Material Supply to End Products
The global high-purity luteolin market in 2025 will feature a surge in demand and a breakthrough in domestic production:

Market Size and Growth:
The global market size is projected to increase from US$420 million in 2024 to US$580 million in 2025, a 38% annual growth rate. China, as the core consumer market, accounts for 35% of this market, with dietary supplements accounting for over 70% of this market.
Competitive Landscape:
International Dominance: Germany's PhytoLab and the United States' Indena dominate the high-end market (purity ≥98%), with product prices ranging from US$1,200 to US$1,800 per kg. Leveraging stringent compliance certifications (FDA GRAS and EFSA certification), they dominate mainstream European and American channels. The Rise of Domestic Products: Companies like Shaanxi Huike and Zhejiang Kangenbei have achieved breakthroughs in purification technology, reducing the price of 98% pure products to $800-1000/kg. These products have passed FSSC 22000 certification and entered the supply chains of leading domestic brands such as By-Health and Infinitus.

Driving Factors:
Under the natural health trend, the growth rate of "plant-extracted + precise function" supplements has reached 25% (compared to only 8% for conventional vitamins). Furthermore, research breakthroughs in luteolin in areas such as post-COVID-19 immune regulation and metabolic syndrome management (120 new related articles in PubMed in 2024) are further driving demand.

VI. Product Selection and Application: A "Technical Guide" for Dietary Supplement Development
1. Core Selection Criteria
Purity and Activity:
Prioritize products with a purity of ≥98% and an isomer content of ≤1% as determined by HPLC to ensure functional consistency. Verify antioxidant activity (free radical scavenging rate ≥90%) using the DPPH assay to avoid oxidative degradation products. Dosage Form Compatibility:
For beverages and granules requiring high water solubility: Choose sulfonated derivatives (increasing water solubility to 50 mg/mL), but the degree of sulfonation should be controlled (≤10%) to maintain activity.
For capsules and tablets requiring sustained release: Choose microencapsulated products (encapsulation efficiency ≥70%) with a release half-life controlled to 4-6 hours, suitable for long-term intervention.

Compliance Qualifications:
Food-grade raw material certification (compliant with GB 1886.319-2022), third-party testing reports (heavy metals, pesticide residues, microorganisms), and a toxicological safety assessment report are required.
2. Key Production Process Points
Formula Stability:
Avoid direct contact with metal ions (such as iron and copper). 0.05% EDTA can be added as a chelating agent to prevent oxidative discoloration.
Control the finished product moisture content to ≤5%, use aluminum-plastic blister packaging (oxygen transmission rate ≤0.1 cc/day), and use an oxygen absorber for a shelf life of up to 36 months. Process Compatibility:
5% microcrystalline cellulose was added as a disintegrant during tableting to prevent tablet splitting (friability ≤ 1%).
0.1% xanthan gum was added to the liquid dosage form for thickening and sedimentation prevention (no delamination in a 3-month accelerated test at 40°C).
VII. Future Trends: From Deepening Functionality to Innovative Industrial Ecosystems
Functional Synergy and Precision Formulation
Multi-target Combination: Developing a ternary formula of luteolin, resveratrol, and coenzyme Q10. Through synergistic regulation of anti-inflammatory, antioxidant, and energy metabolism effects, it improves cardiovascular health indicators (such as hs-CRP) by 50%.
Personalized Customization: Differentiated dosage designs (100-600 mg/day) based on genetic testing (such as Nrf2 gene polymorphisms) enable "on-demand supplementation" and improve intervention precision. Green Production and Sustainable Development
Waste Utilization: Luteolin is extracted from chrysanthemum processing waste (calyx and stems). Microwave-assisted extraction increases the yield to 0.6%, reducing costs by 30% compared to traditional processes while also reducing agricultural waste emissions.
Low-Carbon Extraction: Utilizing a solar-powered supercritical extraction system, energy consumption is reduced by 45% and carbon emissions by 50%, aligning with the "dual carbon" goals.
Emerging Applications
Oral Beauty: Formulated with collagen peptides, it inhibits matrix metalloproteinase (MMP-1) activity (reduced by 42%), reducing skin collagen loss and supporting the "internal nourishment and external nourishment" beauty philosophy.
Pet Health: Developing a supplement specifically for dogs and cats (50-100 mg/day) to improve joint inflammation in elderly pets (increasing mobility by 25%) and expand the companion animal health market.

The rise of 98% high-purity luteolin is fundamentally a reflection of how the "precision natural product" approach is reshaping the dietary supplement industry. Through green extraction and high-precision purification, traditional botanical ingredients are transformed into highly bioavailable "functional factors" with well-defined targets. From immune regulation to neuroprotection, from metabolic health to skin protection, its natural, effective, and safe properties are driving the evolution of dietary supplements from "general nutrition" to "precision intervention." In the future, with in-depth research on its functional mechanisms and breakthroughs in industrialization technologies, luteolin will become a core ingredient in the natural health industry, providing critical support for personalized nutrition and preventive medicine.