Antioxidants. Tomorrow s vision...today!

Antioxidants Tomorrow s vision...today!

Table of Contents Introduction...3 Mitochondrial Theory of Aging...4 Free Radical Damage...5 Enzymatic Antioxidants...6 Product Recommendations...7 Non-Enzymatic Antioxidants...8 Product Recommenations...9 Polyphenols...10 Product Recommendations...11 Sample Formulations...12 Pollution Protection Moisture Cream...13 Revitalizing Antioxidant Face Mask...14 References...15 Version#1/12.27.18

Introduction It is impossible to stop aging, but it is possible to slow down the signs of aging. Antioxidants are the key players in defending against aging skin. They protect, prevent and even reverse signs of aging, while establishing a well-balanced environment for a healthy skin metabolism. Oxidative stress is one of the main reasons why lines and wrinkles appear on the skin along with many other skin issues. The process of oxidation occurs constantly in nature. Even in strong metals, such as iron, oxidation leads to rusting and loss of strength if the metal is not covered with a protective coating. Similarly, oxidative stress causes damage to the skin s vital components. 1 This process is often defined as harmful because the oxygen free radicals attack biological molecules such as proteins, lipids and DNA, causing irreversible damage. These oxidants are reactive oxygen species (ROS) commonly produced by intrinsic essential processes, and boosted by extrinsic contributing factors, including x-rays, ozone, cigarette smoke, air and industrial pollutants. Oxidative stress occurs when number free radicals exceed the amount of antioxidants. However, ROS are not always bad! They enable inter-and intracellular signaling, and induce a multitude of cellular responses depending on their concentration, subcellular localization and lifetime. From a human perspective, too much of anything is bad! A balance between oxidants and antioxidants is necessary for a proper functioning system. As illustrated in Figure 1, oxidative stress occurs when the concentration of reactive oxygen species and free radicals exceed the amount of antioxidants in the metabolism. Figure 1: Significant imbalance leads to oxidative stress.

Mitochondrial Theory of Aging Oxidative stress triggers damage that leads to aging, yet a common misconception is that the largest threat of oxidative stress is our environment. The latest anti-aging research indicates that our mitochondria are the primary source of oxidation that contributes to aging. 2 Oxidative phosphorylation is the metabolic process that fuels the production of Adenosine Triphosphate (ATP), the major source of energy for our cells. This pathway, also referred to as the electron transport system, transfers electrons from electron donors to electron acceptors (oxygen). This is analogous to a bowling ball rolling down a case of stairs that generates energy each time it hits a step. These redox reactions are carried out by a series of five mitochondrial protein complexes collectively referred to as the electron transport chain (Figure 2). As the electrons are passed throughout the chain, energy is generated that is used to make ATP. 2 Normally, oxygen, the final electron acceptor, is reduced to water. However, leakages occur in the system that generates the formation of damaging oxy, hydroxyl and superoxide radicals instead of water. Given the intricate structure of mitochondria and their proximity to the toxins that are produced, mitochondria along with mitochondrial DNA (mtdna) are the most vulnerable and susceptible to damage. In fact, ROS produced by mitochondria pose more of a risk and trigger aging more than environmental ROS. 2 Figure 2: ROS formation in the ETC.

Free Radical Damage ROS is a general term used to describe reactive molecules and free radicals. Generally, highly damaging ROS are hydroxyl radicals, superoxide anion radical, hydrogen peroxide radical, oxygen singlet, hypochlorite, nitric oxide radical, and peroxynitrite radicals. Oxygen containing free radicals are considered to be the most damaging due to the high relative energy of molecules and the number of unpaired electrons. These ROS cause irreversible damage to main biological components such as proteins, lipids and nucleic acids. As shown in Figure 3, continuous free radical damage leads to oxidative stress and cell death. Figure 3: Free Radical Attack Mitochondrial DNA is the most susceptible to damage due to the proximity of oxy radicals in the mitochondrial membrane. Oxidative damage to nucleic acids, such as DNA and RNA, cause permanent changes in the genetic material. The constant replication of modified DNA leads to the accumulation of damaged cells resulting in aging. 3 Protein oxidation commonly involves peroxyl radical damage to specific amino acid sequences, free radical mediated peptide cleavage, and the formation of protein cross-linkage. 3 Protein oxidation affects the alteration of the signal transduction mechanism, enzyme activity, heat stability, and proteolysis susceptibility, which leads to cellular aging. Lipid peroxidation occurs in polysaturated fatty acids located in cellular membranes. Hydroxyl radicals are involved in the initiation of lipid peroxidation, which propagates through a chain of radical reactions leading to the formation of alkanes, malondialdehyde and isoprotane. These compounds are used as markers in lipid peroxidation assay and have been verified in many diseases such as neurogenerative diseases, ischemic reperfusion injury, and diabetes. 3

Enzymatic Antioxidants A unique category of antioxidants, only involved in detoxification of cellular oxidative stressors are enzymes, produced endogenously as primary free radical defenders. 4 Superoxide dismutase (SOD) and glutathione peroxidase (GPX) are free radical specific enzymes. 4 SOD is an important endogenous antioxidant which nullifies superoxide radicals and as a result, hydrogen peroxide is produced. 4 GPX rapidly attacks hydrogen peroxide and peroxide radicals, converts them to alcohol, water and oxygen molecules. 4 Superoxide Dismutase SOD, an oxido-reductase, occurs in three forms, each defined by the metals present. Cu/Zn SOD is the most stable form and the most commonly used in cosmetics. Unlike Vitamin E, Vitamin C, or other antioxidants such as polyphenols, SOD is an enzyme and is not consumed in the process of neutralizing free radicals. Enzymes work like small machines continuously processing while suitable substrate and conditions are available. SOD does not generally react with free radicals, only the superoxide anion. The enzyme targets a specific harmful molecule, making truly smart cosmetic products possible. Glutathione Peroxidase Glutathione is a low molecular weight, thiol-bearing, free-radical scavenger that decreases within the epidermis of aged and damaged skin. In order to reverse this imbalance, it is imperative to restore glutathione levels. Improving and increasing glutathione levels can help convert the oxidized molecules back to their reduced state. 5 Glutathione plays a key role in cellular defenses against reactive oxygen species via limiting cell damage, boosting white blood cell production, and supporting other antioxidants within the body. Elevating cellular glutathione levels can help combat inflammation, preserve overall cell health, and slow the signs and symptoms of aging.

Enzymatic Antioxidants Product Code & Name INCI Name Mechanism Multifunctional Benefits 60101PF AC SOD Liposome PF 20757PF AC CytoPure PF Water & Phospholipids & Superoxide Dismutase Crypthecodinium Cohnii Extract SOD is the master antioxidant of our body, works by neutralizing superoxide anions. Liposomal delivery of SOD optimizes the activity while enhancing powerful antioxidant benefits. Activates the power of glutathione to cleanse cellular pollution and detoxify skin from within. Soothes skin Hair color protection Antioxidant protection Cellular detoxification Pro-collagen synthesis Anti-pollution 20351PF Wasabi Extract PF Lactobacillus/Wasabia japonica Root Ferment Extract Increases Superoxide Dismutase activity, which works by neutralizing harmful superoxide radicals to prevent cellular damage. Antimicrobial Potent antioxidant Good for skin and hair 20357PF Ox-Red Soy Peroxidase PF Soybean Peroxidase Harnesses the enzymatic power of Superoxide Dismutase to effectively reduce irritation while preventing against color fade. Anti-irritant Good for problem skin Intense antioxidant 20395PF AC Sebum Control Enzyme PF Butylene Glycol & Water & Spiraea Ulmaria Extract Reduces the activity of the sebaceous glands by inhibiting the activity of 5α-reductase. Shine agent Maintains young, healthy looking skin Tightening 16670 AC Moisturezyme Protect Citrus Sinensis (Orange) Fruit Extract & Aloe Barbadensis Leaf Extract In a two-step reaction the SOD from blood oranges converts the superoxide anion into hydrogen peroxide, then the peroxidase from aloe converts the hydrogen peroxide into water. Moisturizing Conditioning Superfruit

Non-Enzymatic Antioxidants Vitamin A is an important oil soluble antioxidant that is involved in cell production and growth. 3 B-carotene, the most prominent form of vitamin A derived from plants, is able to act as a lipid radical scavenger and singlet oxygen quencher. 5 B-carotene is able to reduce mitochondrial mutation in human dermal fibroblasts after UV exposure. 5 Therefore, increasing collagen synthesis and speeds up healing process of the skin. 5 Vitamin C, also named L-ascorbic acid, is a powerful water soluble anti-oxidant. Citrus fruits and vegetables are rich in vitamin C. This essential antioxidant is not synthesized in the body, therefore, consumption of vitamin C is critical for health and immune system. Topical use of L-ascorbic acid improves overall skin health and appearance by brightening, protecting and strengthening. Vitamin E, also known as tocopherol, is a naturally occurring endogenous anti-oxidant, which gets depleted over time due to aging and environmental pollution. In addition to anti-oxidant properties, tocopherol helps against collagen crosslinking and lipid peroxidation, which are related to skin aging. 3

Non-Enzymatic Antioxidants Product Code & Name INCI Name Mechanism Multifunctional Benefits 10550 ABS Moringa Pterygosperma Seed Extract G 60104PF AC Vitamin ACE Liposome PF 20248 AC Repair Oil Complex 20478 AC Royal Jelly Extract 20717 AC Love Complex PF 20036 ACB Kale Protein Blend 20024 ACB Wakame Bioferment Advanced Glycerin & Moringa Pterygosperma Seed Extract Water & Phospholipids & Retinyl Palmitate & Tocopheryl Acetate & Ascorbyl Palmitate Helianthus Annuus (Sunflower) Seed Oil & Glycine Soja (Soybean) Oil & Anthemis Nobilis Flower Oil & Lavandula Angustifolia (Lavender) Oil & Rosmarinus Officinalis (Rosemary) Leaf Oil & Calendula Officinalis Flower Extract & Tocopheryl Acetate & Retinyl Palmitate & Bisabolol Butylene Glycol & 10-Hydroxydecanoic Acid & Sebacic Acid & 1,10-Decanediol Water & Phospholipids & Olea Europaea (Olive) Fruit Oil & Ascorbyl Palmitate & Tocopheryl Acetate & Retinyl Palmitate & Linoleic Acid & Lycopene Hydrolyzed Kale Protein & Hydrolyzed Carrot Protein & Hydrolyzed Lemon Protein Undaria Pinnatifida Cell Culture Extract The moringa seed boasts high levels of powerful antioxidants such as Vitamin C, beta carotene, iron, and potassium and is uniquely suited for cosmetic applications because of its botanical appeal. Encapsulation of these vitamins A, C and E in liposomes increases the stability of the vitamins. Combines the benefits of sunflower, soybean, English chamomile, lavender, rosemary leaf oils with calendula extract and vitamins A and E to help repair and condition the skin. The vitamins E, C, B and minerals in royal jelly help to keep the skin hydrated and moisturized, an essential aspect of fighting wrinkles and aged, tired skin. The combination of Lycopene, Olive oil, Vitamins, and Essential fatty acids deliver all the ingredients necessary to protect, condition, nourish and soften the skin and hair. Kale is packed full of vitamin A and E, known to work together to boost hydration, elasticity, and collagen production. This product targets the mitochondria, which has been shown to contribute to the longevity of cells and minimize damage at a cellular level. Skin conditioning Increases barrier protection Natural vitamins and minerals Nourishing Conditioning Enhanced delivery Stimulates collagen synthesis Antioxidant Wound healing Anti-aging Antioxidant protection Moisturizing Antioxidant Anti-aging Moisturizing Moisturizing Volumizing Film-former Anti-aging Increases collagen synthesis Anti-Polution

Polyphenols Among different antioxidants, most powerful are polyphenols, abundant in flora. The human body is not capable of polyphenol synthesis, therefore, consumption and topical use is a must. Structurally, polyphenols consist of more than one aromatic ring and hydroxyl functional groups. Functional groups identify their functionality and strength - the more complex the structure, the more powerful antioxidative properties polyphenols will exhibit. Anti-immunosuppressive, anti-aging, and antioxidant are observed qualities of polyphenols that elevate their prominence within other phytochemicals. Antioxidative action begins with neutralizing superoxide anion radicals, hydroxyl radicals and lipid radicals, preventing intracellular damage. Additionally, antioxidants inhibit lipid peroxidation, DNA damage, and toxic build up while promoting healthy cell and fibroblast production, which positively influences collagen synthesis. There are several subcategories of polyphenols which exhibit antioxidant properties, including: flavonoids, flavones, catechins, phenolic acid, isoflavones and many others that exhibit similar properties.

Polyphenols Product Code & Name INCI Name Mechanism Multifunctional Benefits 10229 ABS White Willow Bark Extract Powder Salix Alba (Willow) Bark Extract Standardized for natural salicylates, delivers the benefits associated with salicylic acid without the irritating side effects. Exfoliation Antimicrobial Increases cellular renewal 16882 Phytofuse Rejuvenate Salvia Hispanica Seed Extract The natural polysaccharides derived from chia seed mucilage promote notable wound healing anti-inflammatory, and film forming. Wound healing Anti-inflammatory Film-former 16810 ACB Pisum Sativum Peptide 20433PF ACB Bamboo Isoflavones PF 20228 ACB Agave HSP 16734 ABS Orange Polyphenols PBF Pisum Sativum (Pea) Peptide Lactobacillus/Arundinaria gigantea Leaf Ferment Filtrate Saccharomyces/Agave Americana Leaf Ferment Filtrate Water & Propylene Glycol & Citrus Aurantium Amara (Bitter Orange) Flower Extract Utilizes the natural benefits of hydrolyzed pea proteins to deliver exceptional volumizing and anti-aging benefits. Bio-chelated silica and isoflavones from bamboo help increase epidermal slip by more than 60%, deliver strong antioxidant benefits to protect the skin and stimulate cellular proliferation. Heat-shock proteins from agave plants help maximize epidermal hydration while stimulating collagen synthesis for optimal antiaging benefits. A lipolytic active ingredient that inhibits the activity of the enzyme phosphodiesterase and catalyzes the production of cyclic AMP (camp). Volumizing Smoothing Anti-aging for skin and hair Enhances slip Antioxidant Natural silicone alternative Sunburn relief Wound healing Increases collagen synthesis Anti-Aging Antioxidant Good for Skin and Hair 40600 Phyto-Biotics Perilla Perilla Frutescens Extract Harnesses the power of Rosmarinic acid to deliver natural antimicrobial, antioxidant and anti-inflammatory properties. Soothes skin Anti-inflammatory Improves cellular metabolism 10247 ABS Pomegranate Sterols Punica Granatum Sterols Lipid fractions produce increased moisture levels and a protective barrier from environmental stressors. Moisturizing Improves barrier function Functional active

Sample Formulations Tomorrow s vision...today!

Polution Protection Moisture Cream Trade Name INCI Name % Vendor Phase A Deionized Water Water 42.40 Local Liposorb L-20 Polysorbate 20 1.00 Vantage Phase B Glycerin U.S.P. Natural 96% Glycerin 4.00 Cognis Corp. KELTROL CG Xanthan Gum 0.20 CP Kelco Phase C Dermol 25B C12-15 Alkyl Benzoate 23.15 Alzo International Inc. TNSS75MZCM Zinc Oxide (And) Ethylhexyl Methoxycrylene (And) C12-15 Alkyl Benzoate (And) Polyhydroxystearic Acid (And) Hydrogen Dimethicone 9.80 Kobo Products Phytomulse Coconut Cetearyl Alcohol & Glyceryl Stearate & Coceth-20 3.45 Active Concepts AcquaSeal Coconut Cocos Nucifera (coconut) Fruit Extract 0.50 Active Concepts Phase D MSS-500W Silica 3.00 Kobo Products Sepigel 305 Polyacrylamide (And) C13-14 Isoparaffin (And) Laureth-7 1.00 ChemyUnion/SEPPIC Phase E PhytoFuse Rejuvenate Salvia Hispanica Seed Extract 2.00 Active Concepts ACB Wakame Bioferment Advanced Undaria Pinnatifida Cell Culture Extract 1.00 Active Concepts AC DermaPeptide Tightening PF Hydrolyzed Wheat Protein 2.00 Active Concepts AC CytoPure PF Crypthecodinium Cohnii Extract 2.50 Active Concepts ACB Agave HSP Saccharomyces/Agave Americana Leaf Ferment Filtrate 2.00 Active Concepts Phase F Leucidal SF Complete Lactobacillus Ferment & Lactobacillus & Cocos Nucifera (coconut) Fruit Extract 2.00 Active Micro Technologies Formulation Guidelines 1. Combine Phase A into main beaker and heat to 70 C. 2. In a separate container, combine Phase B ingredients into a slurry. Add Slowly to Phase A while mixing. 3. In a separate container, combine Phase C ingredients and heat to 70 C. 4. Add Phase C and D to main beaker while cooling to 45 o C. 5. Once cooled, add Phases E and F to main beaker.

Revitalizing Antioxidant Face Mask Trade Name INCI Name % Vendor Phase A Deionized water Water (Aqua) 58.2 Local Tetrasodium EDTA Tetrasodium EDTA 0.05 Spectrum Chemical Keltrol CG Xanthan Gum 0.15 CP Kelco Veegum Ultra Magnesium Aluminum Silicate 4.50 Vanderbilt Minerals, LLC Glycerin Glycerin 4.00 Spectrum Chemical Polysorbate 60 Polysorbate 60 1.00 Spectrum Chemical Phase B Emulsifying Wax Cetearyl Alcohol (and) Polysorbate 60 1.00 Koster Keunen, Inc. Arlacel 40 Sorbitan Palmitate 1.50 Cetyl Alcohol Cetyl Alcohol 0.70 Spectrum Chemical Octyl Palmitate Octyl Palmitate 3.50 Phase C Leucidal Liquid SF Max Lactobacillus Ferment 3.00 Active Micro Technologies Kaolin Kaolin 3.00 Charkit Chemical Corp. Vanatural Bentonite 6.00 Vanderbilt Minerals, LLC Titanium Dioxide Titanium Dioxide 3.00 Spectrum Chemical Phase D AC Moisturezyme Protect Citrus Sinensis (Orange) Fruit Extract & Aloe Barbadensis Leaf Extract 5.00 Active Concepts ACB Modified Pumpkin Enzyme PF Lactobacillus/Pumpkin Fruit Ferment Filtrate 5.00 Active Concepts Fragrance Fragrance q.s. Formulation Guidelines 1. Dissolve EDTA in water and disperse the Keltrol while beginning to heat to 70 o C. 2. Add glycerin, Veegum, and Polysorbate 60 in water phase and heat to 70 o C. 3. In a separate vessel, add Phase B. Heat to 70 o C. 4. Add Phase B to Phase A when both are at 70 o C and thoroughly mixed. 5. Cool to 60 o C and add Phase C. Mix thoroughly to distribute the clays. Mix until smooth. 6. Cool to room temperature and add Phase D.

References 1. Ganceviciene, R., Liakou, A. I., Theodoridis, A., Makrantonaki, E., & Zouboulis, C. C. (2012, July 01). Skin antiaging strategies. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3583892/ 2. Harman, D. The Official Journal of the American Aging Association. Free radical theory of aging: consequences of mitochondrial aging. 1983. 6(3):86-94. 3. Lobo, V., Patil, A., Phatak, A., & Chandra, N. (2010, July). Free radicals, antioxidants and functional foods: Impact on human health. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22228951 4. Jeeva, J. S., Sunitha, J., Ananthalakshmi, R., Rajkumari, S., Ramesh, M., & Krishnan, R. (2015, August). Enzymatic antioxidants and its role in oral diseases. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/ articles/pmc4606614/#ref21 5. Schagen, S. K., Zampeli, V. A., Makrantonaki, E., & Zouboulis, C. C. (2012, July 01). Discovering the link between nutrition and skin aging. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3583891/

Tomorrow s vision...today! Active Concepts, LLC Lincolnton, NC. USA www. activeconceptsllc.com Office: +1 (704) 276 7100 info@activeconceptsllc.com Active Concepts S.r.l. Milano ITALY www.activeconcepts.it Tel +39 02 90360719 info@activeconcepts.it Active Concepts Japan Tokyo, JAPAN www.activeconceptsllc.com Tel +813 62311022 info-tokyo@activeconceptsllc.com Active Concepts LLC, Asia Kaohsiung, Taiwan www.activeconceptsllc.com Tel + 886 73599900 info@activeconceptsllc.com.tw