The following scientific references provide supporting research related to immune balance, cellular homeostasis, mitochondrial function, skin barrier integrity, cellular repair, and selected bioactive ingredients used or studied in our research.
These references are provided as scientific background for our R&D concepts and research directions. Individual studies may involve different experimental models, concentrations, delivery systems, or routes of administration and should therefore be interpreted within their respective research context.
The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their discoveries concerning peripheral immune tolerance.
Their discoveries established fundamental mechanisms through which regulatory T cells help control immune responses and prevent the immune system from attacking the body's own tissues.
This provides important scientific background for understanding why normal immune function depends not simply on stronger immune activity, but on appropriate immune regulation, tolerance, and homeostasis.
2025 Nobel Prize — Peripheral Immune Tolerance
https://www.nobelprize.org/prizes/medicine/2025/press-release/?utm_source=chatgpt.com
Scientific Background — 2025 Nobel Prize in Physiology or Medicine
https://www.nobelprize.org/uploads/2025/10/advanced-medicineprize2025-1.pdf?utm_source=chatgpt.com
FOXP3⁺ regulatory T cells are present in the skin and play an important role in maintaining local immune homeostasis and controlling inappropriate inflammatory responses.
Regulatory T Cells Maintain Immune Homeostasis in the Skin — Journal of Experimental Medicine
https://pubmed.ncbi.nlm.nih.gov/18573908/?utm_source=chatgpt.com
Research has also shown that regulatory T cells participate in the coordination of inflammation and tissue repair following skin injury. Experimental depletion of regulatory T cells has been associated with delayed wound closure and re-epithelialization.
Regulatory T Cells Facilitate Cutaneous Wound Healing
https://pmc.ncbi.nlm.nih.gov/articles/PMC4761457/?utm_source=chatgpt.com
Regulatory T Cells in Skin Injury — Tolerance and Tissue Repair
https://pubmed.ncbi.nlm.nih.gov/32358172/?utm_source=chatgpt.com
Regulatory T Cells in Skin Regeneration and Wound Healing — 2023 Review
https://pmc.ncbi.nlm.nih.gov/articles/PMC10591349/?utm_source=chatgpt.com
Immune Regulation · Immune Homeostasis · Controlled Inflammatory Response · Tissue Homeostasis · Repair
Mitochondria are not only responsible for cellular energy production. They also participate in cellular metabolism, redox regulation, signaling, stress responses, inflammation, and maintenance of cellular homeostasis.
Research increasingly links mitochondrial dynamics and dysfunction with skin homeostasis, cellular aging, oxidative stress, and age-associated changes in skin function.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10693346/?utm_source=chatgpt.com
Mitochondria in Skin Health, Aging and Disease
https://pmc.ncbi.nlm.nih.gov/articles/PMC7283348/?utm_source=chatgpt.com
Mitochondrial dynamics, biogenesis, mitophagy, and other quality-control mechanisms work together to maintain mitochondrial homeostasis.
Mitochondrial Quality Surveillance in Skin Aging
https://pubmed.ncbi.nlm.nih.gov/36972842/?utm_source=chatgpt.com
Mitochondrial metabolites, reactive oxygen species, nucleic acids, and other mitochondrial signals can participate in immune and inflammatory signaling.
This establishes an important biological connection among cellular energy, oxidative stress, mitochondrial function, inflammation, and cellular homeostasis.
https://www.nature.com/articles/s41577-022-00760-x?utm_source=chatgpt.com
Mitochondrial Control of Inflammation — Nature Reviews Immunology
NAD⁺ is central to cellular energy metabolism and participates in numerous cellular processes associated with mitochondrial function, oxidative stress responses, DNA repair, and cellular homeostasis.
Research examining the NAD⁺/nicotinamide metabolome in skin has connected NAD⁺ biology with cellular bioenergetics, mitochondrial efficiency, oxidative stress, photoaging, and skin homeostasis.
The NAD⁺/Nicotinamide Metabolome in Skin Homeostasis, Cellular Bioenergetics and Aging
Recent research has directly investigated nicotinamide mononucleotide (NMN) in human skin fibroblasts, including its effects on cellular responses and gene expression associated with aging and skin-cell function.
NMN — Gene Expression and Biological Responses in Human Skin Fibroblasts — 2025
Gastrodin has been investigated in UVB-induced skin-damage models involving oxidative stress, inflammatory signaling, apoptosis, and mitochondrial function.
Gastrodin Composite Hydrogel and UVB-Induced Skin Damage — 2024
Ergothioneine has been studied for its antioxidant and cytoprotective properties and for its effects in UV-induced skin-cell damage models involving keratinocytes, fibroblasts, oxidative stress, cellular senescence, and Nrf2-related pathways.
Ergothioneine and UVB-Induced Keratinocyte/Fibroblast Damage
Ergothioneine — Biological Mechanisms and Potential Applications
Baicalin has been investigated in UVA- and UVB-induced skin photoaging models, including studies involving dermal fibroblasts, collagen, matrix metalloproteinases, oxidative stress, and cellular senescence.
Baicalin Against UVA-Induced Photoaging in Skin Fibroblasts
Baicalin Against UVB-Induced Photoaging — In Vitro and In Vivo
Tea polyphenols, particularly catechins such as EGCG, have been extensively studied in relation to oxidative stress, inflammatory responses, UV-induced skin damage, and photoaging.
Research also identifies stability and bioavailability as important limitations of EGCG, supporting continued investigation into stabilization and delivery technologies.
EGCG in Preventing Skin Photoaging — Scientific Review
Carnosine has been investigated for antiglycation, antioxidant, and skin-protective properties.
Studies involving human skin and topical formulations have examined its relationship with advanced glycation end-products (AGEs), oxidative stress, photoaging, and skin aging.
Topical Carnosine and Advanced Glycation End-Products in Human Skin
Topical / Transdermal Carnosine — Skin Aging Research — 2024
Centella asiatica and its bioactive triterpenes have been extensively studied in dermatological research, including tissue repair, extracellular matrix regulation, inflammatory signaling, and skin-barrier-related applications.
Centella asiatica in Dermatology — Overview
Centella asiatica — Dermatological Evidence and Mechanisms
Topical Centella asiatica — Mechanisms and Clinical Evidence — 2024
Asiaticoside has been investigated in human dermal fibroblasts for its relationship with fibroblast proliferation, extracellular matrix synthesis, and type I and III collagen.
Asiaticoside — Human Dermal Fibroblasts and Collagen Synthesis
Asiaticoside and Madecassoside — Type I & III Collagen in Human Fibroblasts
Taurine transport and accumulation have been identified in human epidermal keratinocytes.
Research has associated taurine with keratinocyte hydration and cellular adaptation to osmotic stress.
Role of Taurine Accumulation in Keratinocyte Hydration
Betaine is a naturally occurring organic osmolyte involved in cellular osmotic regulation.
Betaine and related osmolytes have been investigated in relation to keratinocyte function, tight-junction proteins, cellular hydration, and skin-barrier properties.
Organic Osmolytes, Tight Junction Proteins and Skin Barrier Function
Research has identified a GABA-related biological system in human dermal fibroblasts.
Studies have investigated GABA in relation to hyaluronic acid synthesis, oxidative-stress responses, type I collagen expression, and MMP-1 expression.
GABA-Synthesizing Enzyme GAD67 in Dermal Fibroblasts
GABA and Type I Collagen in Normal Human Dermal Fibroblasts
Topical adenosine has been investigated in human clinical studies evaluating wrinkles, dermal density, elasticity, and skin hydration.
Adenosine — Clinical Study on Wrinkles, Dermal Density, Elasticity and Hydration
Anti-Wrinkle Efficacy of Adenosine-Containing Products
Topical niacinamide has substantial scientific and clinical literature involving skin-barrier function, hydration, pigmentation, photoaging, and other aspects of skin appearance and condition.
Niacinamide — Dermal Delivery Strategies and Clinical Evidence — 2024
Topical Niacinamide and Skin Barrier Enhancement
Arbutin has been studied primarily for its effects on tyrosinase activity and melanogenesis, together with antioxidant-related properties.
Arbutin — Antimelanogenic and Antioxidant Properties
3-O-Ethyl Ascorbic Acid is a vitamin C derivative investigated in relation to oxidative stress, UVA exposure, Nrf2 signaling, melanogenesis, and skin delivery.
3-O-Ethyl Ascorbic Acid — Nrf2, UVA and Melanogenesis
3-O-Ethyl Ascorbic Acid — Skin Delivery Study
Ectoin is a natural extremolyte with water-binding and cellular stress-protection properties. Topical Ectoin formulations have also been evaluated in controlled human skin studies.
Ectoin — Randomized, Double-Blind, Vehicle-Controlled Clinical Study
Topical hyaluronic acid has extensive research relating to hydration, elasticity, barrier condition, and visible signs of skin aging.
Different molecular-weight fractions have also been investigated because molecular size can influence skin interaction and biological behavior.
Topical Hyaluronic Acid — Literature Review and Clinical Evidence
Hyaluronic Acid and Molecular-Weight-Related Skin Applications
Ceramides are essential structural lipids of the stratum corneum and play a central role in skin-barrier organization and water retention.
Ceramide NP-containing topical formulations have been investigated clinically in relation to barrier function and transepidermal water loss.
Ceramide NP — Skin Barrier Clinical Study — 2026
Glabridin, a major bioactive component associated with licorice, has been studied in relation to tyrosinase activity, melanogenesis, UV-induced pigmentation, and inflammatory responses.
Glabridin — Melanogenesis, UV-Induced Pigmentation and Inflammation
Panax ginseng has been investigated in human skin and dermal fibroblast research, including clinical studies examining visible signs of skin aging.
Panax ginseng — Randomized Double-Blind Anti-Wrinkle Study
Panax ginseng — Human Dermal Fibroblast and Human Skin Study
Panax notoginseng saponins have been investigated in cutaneous wound-healing models involving fibroblast responses, wound closure, and scar formation.
Panax notoginseng Saponins — Cutaneous Wound Healing and Scar Formation
Lycium barbarum polysaccharides have been investigated in UVB-induced skin photoaging models involving oxidative stress and skin structural changes.
Lycium barbarum Polysaccharide Against UVB-Induced Skin Photoaging
Recent research has examined Ganoderma lucidum in UVA-induced skin photoaging models involving mitochondrial stress, mitochondrial ROS, and mitochondrial membrane integrity.
Ganoderma lucidum — Mitochondrial Stress and Skin Aging — 2025
Houttuynia cordata has been investigated in relation to inflammatory signaling, oxidative stress, skin inflammation, and barrier damage.
Houttuynia cordata — Skin Inflammation and Barrier Damage
Houttuynia cordata — Inflammation and Oxidative Stress Review
Boswellic acids have been evaluated in a randomized, double-blind, placebo-controlled split-face study involving photoaged facial skin.
Topical Boswellic Acids for Photoaged Skin — Clinical Study
Curcumin has extensive biological research relating to oxidative stress and inflammatory signaling. Topical applications have also been evaluated in clinical studies involving skin conditions and skin health.
Clinical Studies on Topical Curcumin — 2023 Review
Turmeric / Curcumin and Skin Health — Systematic Review of Clinical Evidence
Hesperidin has been investigated in human keratinocytes for its relationship with UVA-induced oxidative stress and inflammatory responses.
Hesperidin — UVA-Induced Skin Oxidative Stress and Inflammation
Recent research has also investigated hesperidin in skin fibroblasts, keratinocytes, and three-dimensional skin models in relation to photoaging and cellular stress mechanisms.
Hesperidin — Skin Photoaging, GPX4 and Ferroptosis — 2026
Additional plant-derived peptides, polyphenols, botanical bioactives, cellular metabolites, osmolytes, and skin-supporting compounds remain under continuing evaluation.
Scientific evidence is reviewed according to the nature of each study, including:
Human Clinical Studies · Human Skin Models · Human Skin Cells · In Vivo Models · In Vitro Studies · Mechanistic Research · Scientific Reviews
Research evidence is evaluated together with bioactive purity, stability, formulation compatibility, delivery characteristics, and effective utilization.
Plant-derived bioactive peptides are short peptide sequences derived from plant proteins through processes such as enzymatic hydrolysis, fermentation, separation, and purification.
Current research indicates that plant-derived bioactive peptides can exhibit diverse biological activities associated with oxidative stress regulation, inflammatory signaling, cellular protection, and other biological functions. Their biological properties depend strongly on peptide source, amino-acid sequence, molecular size, structure, purity, and processing method.
A 2025 review in the Journal of Agricultural and Food Chemistry systematically examined plant-derived bioactive peptides, including their sources, extraction, isolation, purification, biological activities, structure–activity relationships, and applications.
Importantly, the review identifies extraction and purification as major parts of plant-peptide research and discusses their potential applications in food, pharmaceutical, and cosmetic fields.
A 2024 review in Antioxidants examined plant-derived antioxidant peptides, including their sources, structures, biological activities, mechanisms, and applications.
The review discusses several signaling systems associated with oxidative-stress regulation, including Keap1–Nrf2–ARE and NF-κB, and specifically reviews applications of plant-derived antioxidant peptides in cosmetics.
Antioxidant Function and Application of Plant-Derived Peptides — Antioxidants 2024
Of particular relevance to skin research, the review describes studies of plant-derived short peptide mixtures in human skin fibroblasts exposed to UVA-induced oxidative stress, including effects involving ROS, lipid oxidation products, Nrf2 nuclear translocation, and downstream antioxidant enzyme expression.
A 2026 review specifically addressing plant-derived bioactive peptides in anti-aging research examines multiple proposed biological mechanisms as well as delivery limitations and strategies designed to improve effective utilization.
Plant Protein → Peptide Generation → Separation & Purification → Low-Molecular-Weight Bioactive Peptides → Stability & Delivery → Biological Utilization
This body of research provides scientific background for our continuing investigation of purified, low-molecular-weight plant-derived bioactive peptides, rather than treating conventional botanical extracts and plant peptides as equivalent materials.
Glycine is the smallest amino acid and is a fundamental structural component of collagen. Approximately one-third of the amino-acid residues in collagen are glycine, reflecting its essential structural role in formation of the collagen triple helix.
More importantly, experimental research has examined whether glycine availability itself can influence collagen production in human dermal fibroblasts.
A 2022 study compared 20 naturally occurring free amino acids in human dermal fibroblasts. Among those tested, glycine produced the strongest increase in collagen production, followed by several other amino acids.
Glycine, Glycinamide and Collagen Production in Human Dermal Fibroblasts — Biomedicines 2022
The same research further investigated glycinamide and vitamin C. Glycinamide produced a stronger collagen response than glycine in this experimental model, while combining glycinamide with ascorbic acid further enhanced collagen production and wound closure in cultured human dermal fibroblasts.
This study is especially relevant because it distinguishes between the simple fact that glycine is a structural component of collagen and the experimentally observed effects of glycine availability on collagen production by dermal fibroblasts.
Citicoline (CDP-choline; cytidine diphosphate-choline) is an intermediate associated with phosphatidylcholine biosynthesis and has been extensively investigated in cellular membrane, neurological, and cytoprotective research.
Current evidence directly related to topical human skin application remains limited. However, cellular research provides useful scientific information concerning citicoline, oxidative stress, mitochondrial function, membrane biology, and cellular homeostasis.
A 2026 study using hypoxia-exposed human scleral fibroblasts found that citicoline treatment was associated with:
Reduced intracellular ROS
Increased glutathione levels
Increased SOD activity
Reduced MDA accumulation
Preservation of mitochondrial membrane potential
Changes associated with ER-stress regulation and cellular homeostasis
Because these were human scleral fibroblasts rather than dermal fibroblasts, this study is best regarded as cellular and mechanistic evidence rather than direct evidence of topical skin efficacy.
Another study used transmitochondrial human retinal pigment epithelial cells carrying mitochondria from patients with age-related macular degeneration.
Citicoline treatment reduced ROS and apoptotic responses and improved cell viability in this in-vitro cellular model.
Role of Citicoline in an In Vitro Mitochondrial Cellular Model
Additional cellular research has also shown protection of mitochondrial membrane potential under oxidative stress.
Citicoline — Oxidative Stress and Mitochondrial Membrane Potential
Therefore, the present scientific relevance of Citicoline to our research is primarily:
Cell Membrane Biology · Oxidative Stress · Mitochondrial Function · Cellular Stress Response · Cellular Homeostasis
rather than established topical cosmetic efficacy.
13 · BETAINE · TAURINE & CELLULAR OSMOTIC HOMEOSTASIS
Betaine and taurine belong to a class of naturally occurring compounds known as organic osmolytes, which participate in cellular adaptation to osmotic stress and maintenance of intracellular water balance.
Human skin research has demonstrated transport systems for both betaine and taurine in skin and keratinocytes.
Treatment of human skin with betaine or taurine increased the expression of the tight-junction proteins claudin-1, claudin-4, and occludin. Both osmolytes also increased tight-junction function in primary human keratinocytes.
Earlier research on normal human keratinocytes also demonstrated an osmolyte strategy involving betaine, taurine, and other osmolytes. Exposure to hyperosmotic conditions and UV radiation altered osmolyte transporter expression and uptake, supporting their relationship with cellular volume homeostasis and environmental stress responses.
The Osmolyte Strategy of Normal Human Keratinocytes in Maintaining Cell Homeostasis
This is particularly relevant to the concept of the cellular microenvironment, because osmotic homeostasis, cellular hydration, protein stability, tight-junction organization, and epidermal barrier function are interconnected rather than isolated processes.
Betaine · Taurine · Osmotic Homeostasis · Keratinocyte Function · Tight Junctions · Epidermal Barrier
Scientific evidence surrounding bioactive ingredients exists at different experimental levels. We therefore do not treat all references as equivalent.
The research presented in this section may include:
Human Clinical Studies
Human Skin Studies
Ex Vivo Human Skin Models
Human Dermal Fibroblasts / Keratinocytes
Other Human Cell Models
In Vivo Experimental Models
In Vitro Mechanistic Studies
Systematic Reviews & Scientific Reviews
A biological effect observed in a cellular model does not automatically establish the same effect in human topical application.
At the same time, mechanistic and cellular studies remain important for understanding relationships among:
Immune Homeostasis · Cellular Microenvironment · Mitochondrial Function · Oxidative Stress · Cellular Energy · Skin Barrier · Extracellular Matrix · Cellular Repair
Our R&D approach therefore considers scientific evidence together with the actual characteristics of the bioactive material, including:
Purity · Effective Concentration · Molecular Size · Stability · Formulation Compatibility · Delivery · Release · Effective Utilization