highly pure Fucosyllactose extracted from human milk oligosaccharide that has been extensively studied for its topical benefits including anti-irritation and skin whitening

Bioactive-2FL™ is highly pure Fucosyllactose extracted from human milk oligosaccharide that has been extensively studied for its topical benefits including anti-irritation and skin whitening.

Below are the summary of the attached research papers.

1. The protective effects of two human milk components, 2'-fucosyllactose (2'-FL) and osteopontin (OPN), against atopic dermatitis (AD) in mice. AD is a chronic inflammatory skin disease characterized by itchy, inflamed skin that is common in infants. The researchers examined whether oral administration of 2'-FL and OPN could ameliorate AD symptoms in a mouse model of the disease

Key findings:

1. AD model and treatment:

• AD-like symptoms were induced in BALB/c mice by applying 2,4-dinitrochlorobenzene (DNCB) to their skin.
• Mice were orally administered 2'-FL (600 mg/kg/day), OPN (37.5 mg/kg/day), or both for 21 days.

2. Effects on AD symptoms:

• 2'-FL and OPN treatment significantly reduced ear thickness, skin lesion severity, and epidermis thickness in AD mice.
• The combination of 2'-FL and OPN showed greater beneficial effects than either component alone.
• Treatment restored expression of skin barrier proteins filaggrin and keratin-10 in AD mice.
• Scratching behavior was significantly reduced in treated mice.

3. Immunological effects:

• Serum IgE levels were markedly decreased in treated AD mice.
• Infiltration of mast cells and eosinophils in skin lesions was reduced.
• Expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and thymic stromal lymphopoietin (TSLP) was suppressed in skin lesions.
• The Th2 immune response was inhibited, with reduced IL-4 producing CD4+ T cells in draining lymph nodes and decreased IL-4 and GATA3 expression in skin.

4. In vitro effects:

• 2'-FL and OPN directly inhibited differentiation of naive CD4+ T cells into Th2 cells in vitro.

The researchers concluded that 2'-FL and OPN ameliorate AD pathology by limiting IgE levels, suppressing mast cell and eosinophil infiltration, and inhibiting Th2 immune responses. They suggest these human milk components may help prevent AD in infants.

Background and rationale: The study was motivated by previous research showing anti-inflammatory properties of human milk components like 2'-FL and OPN. Clinical trials have found that infants fed formula supplemented with these components have lower levels of inflammatory markers. The researchers wanted to specifically investigate their effects on AD, given its high prevalence in infants.

AD is characterized by skin barrier dysfunction and aberrant immune responses, particularly overactivation of Th2 cells. Th2 cytokines like IL-4 and IL-13 drive AD pathogenesis by compromising skin barrier integrity and promoting inflammation. Therefore, the researchers focused on how 2'-FL and OPN might modulate Th2 responses.

Methodology: The study used a well-established mouse model of AD, induced by repeated application of DNCB to the skin. This model mimics key features of human AD including elevated IgE, skin inflammation, and Th2-biased immune responses.

The researchers comprehensively evaluated AD symptoms and underlying immunological changes:

• Skin pathology: Ear thickness, dermatitis scoring, histological analysis
• Scratching behavior
• Serum IgE levels
• Mast cell and eosinophil infiltration in skin (histology)
• Inflammatory gene expression in skin (RT-PCR)
• T cell responses in draining lymph nodes (flow cytometry)
• In vitro T cell differentiation assays

Results interpretation: The striking reduction in AD symptoms and scratching behavior suggests 2'-FL and OPN have potent therapeutic effects. The researchers attribute this to several immunomodulatory mechanisms:

1. Decreased IgE: Lower IgE levels indicate reduced allergic sensitization, a key driver of AD.
2. Reduced mast cell/eosinophil infiltration: These cells release inflammatory mediators that exacerbate AD. Their reduction likely contributes to decreased inflammation.
3. Suppressed pro-inflammatory cytokines: Downregulation of TNF-α, IL-6, IL-1β in the skin suggests a broad anti-inflammatory effect.
4. Inhibition of TSLP: TSLP from keratinocytes promotes Th2 responses, so its suppression may interrupt the inflammatory cascade.
5. Th2 inhibition: The marked reduction in IL-4-producing T cells and Th2-associated genes (IL-4, GATA3) indicates 2'-FL and OPN specifically target the Th2 response central to AD pathogenesis.
6. Improved skin barrier: Restored expression of filaggrin and keratin-10 suggests the treatments help normalize skin barrier function, addressing a key defect in AD.

The in vitro data showing direct inhibition of Th2 differentiation provides a potential mechanism for the in vivo effects, suggesting 2'-FL and OPN may directly modulate T cell responses.

Significance and implications: This study provides evidence that specific human milk components can ameliorate AD-like inflammation, supporting their potential use in preventing or treating AD in infants. The ability of orally administered 2'-FL and OPN to produce systemic immunomodulatory effects is noteworthy, as it suggests they survive digestion and are biologically active beyond the gut.

The synergistic effects of combining 2'-FL and OPN highlight the potential benefits of multi-component approaches that may more closely mimic the complex composition of human milk.

By elucidating the immunological mechanisms of 2'-FL and OPN, particularly their effects on Th2 responses, this research contributes to understanding how human milk components shape infant immune development. It also provides insights into potential therapeutic targets for AD.

Limitations and future directions: The researchers acknowledge some limitations of their study:

• The DNCB-induced mouse model, while useful, may not fully replicate human AD.
• The sample size was limited.
• The study focused on prevention rather than treatment of established AD.

They suggest future research directions including:

• Testing in spontaneous AD mouse models or human clinical studies
• Investigating the effects on established AD lesions
• Exploring the molecular mechanisms by which 2'-FL and OPN modulate T cell responses
• Examining potential direct interactions with immune cell receptors

In conclusion, this study provides compelling evidence for the protective effects of 2'-FL and OPN against AD-like inflammation in mice, suggesting these human milk components may help prevent AD in infants. The research highlights the immunomodulatory properties of human milk and opens avenues for developing novel strategies to combat AD and other allergic diseases.

2. The effects of 2'-fucosyllactose (2'-FL), a major component of human milk oligosaccharides, on melanin degradation and explored its potential as a safe melanin-degrading agent for treating skin hyperpigmentation.

Key findings:

1. 2'-FL reduced melanin levels in melanocytic cells and a human skin equivalent 3D model:

• Treatment with 2'-FL (10 or 20 g/L) for 24 hours did not significantly affect cell morphology or viability of human melanocytes and MNT-1 cells, indicating low cytotoxicity.
• 2'-FL (20 g/L) significantly decreased melanin levels in mouse B16 cells after 7 days of treatment.
• In a human skin 3D model, 2'-FL (20 or 40 g/L) significantly reduced skin pigmentation after 7 days.

2. Transcriptome analysis revealed 2'-FL's effects on cellular processes and signaling pathways:

• 1151 differentially expressed genes were identified (751 upregulated, 400 downregulated).
• Upregulated processes included Ca2+-dependent noncanonical Wnt signaling, and responses to vitamin D and cAMP.
• Downregulated processes included circadian rhythm and endoplasmic reticulum stress.
• The AMPK-ULK1 axis emerged as a key signaling pathway affected by 2'-FL treatment.

3. 2'-FL induced autophagy via the AMPK-ULK1 signaling axis:

• 2'-FL treatment increased LC3I conversion to LC3II, indicating autophagy activation.
• 2'-FL increased phosphorylation of AMPK (Thr172) and ULK1 (Ser555), while decreasing ULK1 phosphorylation at Ser757.
• Dorsomorphin (DMP), an AMPK inhibitor, blocked 2'-FL-induced AMPK and ULK1 phosphorylation and reduced LC3II accumulation.

4. 2'-FL promoted melanin degradation through autophagosome formation:

• Immunofluorescence analysis showed 2'-FL induced colocalization of the melanosomal marker PMEL and autophagosomal marker LC3.
• DMP treatment prevented 2'-FL-induced autophagosome formation and melanin reduction.

5. In vivo mouse model confirmed 2'-FL's melanin-degrading effects:

• Local application of 2'-FL on mouse feet and tail attenuated UVB-induced pigmentation.
• 2'-FL also increased LC3I to LC3II conversion in vivo.

Mechanism of action: The study proposes that 2'-FL activates the AMPK-ULK1 signaling axis, leading to increased autophagy and melanin degradation. This occurs through the following steps:

1. 2'-FL treatment activates AMPK by increasing phosphorylation at Thr172.
2. Activated AMPK phosphorylates ULK1 at Ser555 and inhibits its inactivation by reducing phosphorylation at Ser757.
3. Activated ULK1 initiates autophagy.
4. Autophagosomes form and fuse with melanosomes, as evidenced by colocalization of LC3 and PMEL.
5. Melanin within the autophagosomes is degraded, leading to reduced pigmentation.

The transcriptome analysis provided insights into the broader cellular context of 2'-FL's effects:

• Upregulation of Ca2+-dependent noncanonical Wnt signaling and cAMP response pathways may contribute to AMPK activation.
• Vitamin D response pathway upregulation could also play a role in autophagy induction.
• Downregulation of ER stress and circadian rhythm pathways may be associated with AMPK signaling and autophagy.

Significance and potential applications:

1. Safe melanin-degrading agent: 2'-FL demonstrated melanin-reducing effects with minimal cytotoxicity, making it a promising candidate for treating hyperpigmentation in cosmetic and medical applications.
2. Novel mechanism: The study reveals a previously unknown function of 2'-FL in regulating autophagy through the AMPK-ULK1 axis, contributing to melanin degradation.
3. Alternative to conventional treatments: Current treatments for hyperpigmentation often have adverse effects. 2'-FL's natural origin and low cytotoxicity make it an attractive alternative.
4. Potential for mass production: 2'-FL can be produced through microbial biosynthesis, facilitating its large-scale production for commercial applications.
5. Broader implications: The study's findings on 2'-FL's effects on cellular signaling pathways may have implications beyond melanin regulation, potentially opening new avenues for research on its other biological functions.

Limitations and future directions:

1. Further investigation is needed to fully elucidate the upstream mechanisms by which 2'-FL activates AMPK.
2. Long-term effects and optimal dosing of 2'-FL for skin applications need to be determined through additional studies.
3. The potential interactions of 2'-FL with other skin care ingredients and its effects on different skin types should be explored.
4. Clinical trials are necessary to confirm the efficacy and safety of 2'-FL as a treatment for hyperpigmentation in humans.
5. The study's findings on 2'-FL's effects on various cellular pathways warrant further investigation into its potential applications beyond melanin regulation.

In conclusion, this study demonstrates that 2'-fucosyllactose, a major component of human milk oligosaccharides, promotes melanin degradation by inducing autophagy through the AMPK-ULK1 signaling axis. These findings suggest that 2'-FL may represent a new, safe, and effective agent for treating skin hyperpigmentation, with potential applications in both cosmetic and medical fields. The study also provides valuable insights into the cellular mechanisms affected by 2'-FL, paving the way for further research into its diverse biological functions and potential therapeutic applications.

How to use: Can be used with all products such as gels, serums, lotions or creams.

Mixing method: mix in water phase. Do not expose to heat above 40C

Usage rate: 0.1-2%

Product characteristics: white to off-white powder

Solubility: Can be dissolved in water.

Storage: Store in the refrigerator at 4 ° C - 8 ° C, shelf life 24 months.

INCI : Fucosyllactose