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Anti-wrinkle by antioxidant

04.07.2016

What is wrinkle?

When we're young, we don't have wrinkles because the skin does a great job of stretching and holding in moisture. The dermis has an elastic quality thanks to fibers called elastin that keep the skin looking and feeling young. A protein in the dermis called collagen also plays a part in preventing wrinkles. However, over time, the dermis loses both collagen and elastin, so skin gets thinner and has trouble getting enough moisture to the epidermis. The fat in the subcutaneous layer that gives skin a plump appearance also begins to disappear, the epidermis starts to sag, and wrinkles form. Eventually, however, everyone will have at least a few wrinkles. It's a natural part of the aging process.

Anti-wrinkle can be categorized into four mechanisms:

Reactive oxygen species (ROS) cause damage to lipids, proteins and DNA and also influence cellular senescence. Low doses of H2O2 have been shown to cause cells to enter a senescent-like state. The epidermis of skin possesses a very efficient antioxidant activity that is superior to most tissues and the drop in efficiency of this system has been anticipated as a factor in skin aging. Aging is also mainly influenced by external oxidative stresses that influence the genetic program by modulation of redox sensitive genes.

What products can be used for anti-wrinkle?

Vitamin E

The antioxidant function of vitamin E is thought to mediate its photo-protective effects. Cyclooxygenase-2 (COX-2) is an important mediator of early photo-inflammation. Thus, the ability of γ-tocopherol to inhibit COX-2 activity independently of its antioxidant function raises important questions regarding potential roles that this form of vitamin E plays in photo-protection and skin cancer chemoprevention.

Tocopherols are chemical compounds that comprise a chromanol ring and a hydrophobic side chain of an isoprene molecule, and are present in eight different forms based on the distinct substituted position of the methyl group in the chromanol ring and by the distinct unsaturation of the hydrophobic side chain. The antioxidative mechanism of tocopherols is partially due to the hydroxyl group in the chromanol ring donating a hydrogen atom to reduce free radicals.

Under physiologic conditions, α-tocopherol stimulates the GSH(Glutathione) synthesis in HaCaT keratinocytes through the upregulation of glutamyl cysteine synthetase mRNA. This finding suggests that tocopherol has biologic effects through the modulation of cellular responses.

Tocopherol has preventive effects in various oxidative stress conditions. 12-O-Tetradecanoylphorbol-13-acetate, which is a well-known tumor promoter, induces oxidative stress. Application of tocopherol to the skin 30 min prior to treatment with 12-O-tetradecanoylphorbol-13-acetate inhibits the induction of H2O2, myeloperoxidase activity, xanthine oxidase activity, and lipid peroxidation.

α-Tocopherol is expected to downregulate MMP-1(Matrix Metalloproteinases) through its suppressive effects on AP-1 DNA binding. Dermal fibroblasts isolated from aged donors produce higher levels of MMP-1 than those from young donors. α-Tocopherol attenuates the increased collagenase gene transcription in aging fibroblasts without altering the level of its natural inhibitor, tissue inhibitor of metalloproteinase through the inhibition of protein kinase C a activity. A detailed study of the ROS scavenging activity of tocopherols showed that g-tocopherol is superior toα-tocopherol in its ability to scavenge NO-. Tocopherol, therefore, suppresses melanogenesis.

γ-Tocopherol is useful for suppressing melanogenesis and mRNA expression of tyrosinase and tyrosinase-related protein-2 in melanoma cells. A novel hydrophilicγ-tocopherol derivative was recently synthesized to reinforce its biologic effects. γ-Tocopherol-N,N-dimethylglycinate hydrochloride significantly reduces the formation of edema and tempered the increase in the COX-2-catalyzed synthesis of prostaglandin E induced by UV. Further, γ-tocopherol-N,N-dimethylglycinate hydrochloride strongly suppresses inducible nitric oxide synthase mRNA expression and NO- production.

Vitamin C

Ascorbic acid eliminates most ROS due to the oxidation of ascorbate to monodehydroascorbate and then to dehydroascorbate and has diverse functions to maintain the normal physiologic state in humans. In the skin, ascorbic acid is a cofactor required for the enzymatic activity of prolyl hydroxylase, which hydroxylates prolyl residues in procollagen and in elastin. In addition, ascorbic acid is widely used as a depigmentation agent due to its inhibitory effect on tyrosinase. Recent studies reported newly discovered functions of ascorbic acid that contribute to the formation of the skin barrier by enhancing epidermal differentiation and stimulating blood flow through NO- production via increases in the stability of tetrahydrobiopterin, a cofactor of constitutive NOS(Nitric Oxide Synthase). Study suggests that dark circles on the lower eyelid, which are caused by hyperpigmentation and poor blood circulation, are improved by ascorbic acid. In fact, in an in vivo study, ascorbic acid Na salt significantly improved dark circles due to effects on melanin, erythema, and dermal thickness. These findings demonstrated the effects of ascorbic acid to suppress melanogenesis, to stabilize NOS, and to stimulate collagen synthesis.

Although ascorbic acid is widely applied to the skin to achieve these clinical improvements, its poor skin penetration and its instability in formulations reduce its clinical efficacy to overcome these disadvantages, several ascorbic acid derivatives, such as magnesium L-ascorbyl-2-phosphate, ascorbic acid 2-O-a-glucoside, 6-acylated ascorbic acid 2-O-a-glucoside, and tetra-isopalmitoyl ascorbic acid, have been synthesized and evaluated for their potential as pro-ascorbic acid derivatives.

Carotenoids

Carotenoids are organic pigments that are naturally produced by plants, algae, some types of fungus, and some bacteria. β- Carotene and astaxanthin are components of carotenoids. In general, carotenoids possess the ability to quench oxygen free radicals. The mechanisms are: moderate doses of UVA stimulate fibroblast apoptosis; increase oxidative stress, including ROS generation; decrease antioxidant enzyme activities; promote membrane perturbation; and induce the expression of heme oxygenase-1. Among astaxanthin, canthaxanthin, and β-carotene, astaxanthin pre-loaded in fibroblasts protects against the UVA-induced alterations described above, indicating that astaxanthin has a superior preventive effect towards photo- oxidative changes in cell culture.

The lycopene concentration in skin also correlates significantly with skin roughness, suggesting that higher levels of antioxidants in the skin effectively decrease skin roughness, which is an early stage of wrinkle formation.

Coenzyme Q10

Coenzyme Q10 (CoQ10), which was found only a half century ago, has both energizing and antioxidative effects. CoQ10 is considered to be an effective nutritional supplement that ameliorates skin aging, especially wrinkles. The content of endogenously synthesized CoQ10 in skin decreases with aging. Oral administration of CoQ10 increases the epidermal CoQ10 level, and this is considered to have energizing and antioxidative actions in skin cell. It also increases the CoQ10 concentration in serum and organs, such as the liver, heart, and brain.

Mechanisms of the antiaging effects in skin are:

(1) Promotion of fibroblast proliferation;

(2) Induction of increased production of basement membrane constituents. CoQ10 accelerates the production of basement membrane components, such as laminin 332 and type IV and VII collagens, in keratinocytes and fibroblasts, respectively, however, it has no effect on type I collagen production in fibroblasts. These findings suggest that CoQ10 has anti-aging effects through the accelerated production of epidermal basement membrane components;

(3) Inhibition of cell damage and pigment-generating auto-oxidation through its antioxidative ability.

Oral supplementation of CoQ10 is expected to be effective for “beauty from within,” through its antioxidant and energizing effects in skin.


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