1. No-Tox Botox: Natural Anti-Aging Ingredients Explained
Moderator: Jessica Rubino, Senior Associate Editor, Delicious Living
Dr. Linda Miles, L. Ac. DOM, Derma e Bodycare
Chris Fields, VP Technology & Science NutriCosmetics /AFS
Hyperpigmentation 
Collagen/Elastin 
Fine lines/Wrinkles 
Inflammation
Overall skin health 
It will include a discussion of the latest science for cutting-edge topicals, collagen, and sunscreen

2. No-Tox Botox: Natural Anti-Aging Ingredients Explained
Hyperpigmentation  
Inflammation
Overall skin health 
It will include a discussion of the latest science for cutting-edge topicals, collagen, and sunscreen

3. PhotoDamage – Sun Protection
Reduced Cell Turnover
Cells remain on the surface longer
Cellular mitosis creates abnormal keratinocytes
Epidermal structure becomes disorganized
Melanocytes over-produce melanosomes
Hyperpigmentation
Damaged collagen and elastin weakens dermal connective tissue
Elasticity degradation
Stratum Corneum:
thick and
dehydrated
Skin cells are
Misshaped &
disorganized
Excess melanin
Causing uneven
Skin tone
Collagen & elastin
fibers become weak & damaged

4. Natural Solutions Hydrating Anti-Inflammatory Antioxidants
Depigmenting
Olive Oil
Chamomile
Vitamin A, C, E
Licorice
Colloidal Oatmeal
Coffee Extract
Mulberry
Hyaluronic Acid
Feverfew
Green / Black Tea Extract
Arbutin
Melon Extract
Zinc
Pomegrate
Soy
Krill Oil
Fish Oil
Grape Seed Extract
Aloesin
Sea Buckhorn
COQ10
Acai Berry Extract
Linoleic Acid
Ceramides
Vitamin C
Resveratrol
Niacinamide
Natural Solutions

5. Inflammation
Inflammatory skin diseases are the most common problem in dermatology. They come in many forms, from occasional rashes accompanied by skin itching and redness, to chronic conditions such as dermatitis (eczema), rosacea, seborrheic dermatitis, and psoriasis. Skin inflammation can be characterized as acute or chronic. Acute inflammation can result from exposure to UV radiation (UVR), ionizing radiation, allergens, or to contact with chemical irritants (soaps, hair dyes, etc.). This type of inflammation is typically resolved within 1 to 2 weeks with little accompanying tissue destruction. In contrast, chronic inflammation results from a sustained immune cell mediated inflammatory response within the skin itself. This inflammation is long lasting and can cause significant and serious tissue destruction.  Inflammatory skin conditions affect over 35 million Americans who annually spend over $2 billion to treat their symptoms. 
The process of skin inflammation is complex and is still not completely understood. When the skin is exposed to a "triggering" stimulus, such as UV radiation, an irritant (e.g. soaps or fragrances), or to allergens, the cells in the skin produce a variety of inflammatory "hormones" called cytokines and chemokines. These "inflammatory messengers" bind to specific receptors on target cells and stimulate the production of additional inflammatory signaling "hormones". Some of these cause vasodilation while others activate nerve cells. Still other cytokines cause immune cells to leave the blood and migrate into the skin where they then produce more inflammatory hormones, as well as enzymes, free radicals, and chemicals that damage the skin. The end result of the initial triggering event is the amplification of a large inflammatory response that, while designed to help the skin fight infection from invading bacteria, actually causes considerable damage to the skin

6. Avenanthramide (ug/ml) - MOA
And although typically ingested, oats have been shown to work topically. British researchers at the royal London hospital said topical formulations of natural colloidal oatmeal should be considered an important component of therapy for atopic dermatitis and other conditions, noting it may allow for reduced use of corticosteroids and calcineurin inhibitors.12 Colloidal oatmeal has an extensive history of beneficial use in dermatology. In recent years, in vitro and in vivo studies have begun to elucidate the multiple mechanisms of action of naturally derived colloidal oatmeal. Evidence now describes its molecular mechanisms of anti-inflammatory and antihistaminic activity. The Avenanthramide, a recently described component of whole oat grain, are responsible for many of these effects. Studies have demonstrated that Avenanthramide can inhibit the activity of nuclear factor kappaB and the release of proinflammatory cytokines and histamine, well known key mechanisms in the pathophysiology of inflammatory dermatoses.
Cerio r et al. “Mechanism of action and clinical benefits of colloidal oatmeal for dermatologic practice” J Drugs Dermatol Sep;9(9):
Agents with adjunctive therapeutic potential in atopic dermatitis
Wallo et al, 65th Annual AAD, Feb 2006, Washington DC

7. Avenanthramides- Clinical Evidence
Oat Avenanthramides: new actives to reduce itch sensation in skin. Schmaus
Et al, 23rd Congress of Intr Fed of Soc Cos Chemists, Oct 2006 Orlando FL

8. Mediator Release (TNF-α ICD50 (ug/ml)
Feverfew
Compound
Mediator Release (TNF-α ICD50 (ug/ml)
Feverfew PFE
0.13
Green Tea
4.6
Echinacea 20
Boswelia seratta
24.5
Licorice Extract
54.7
Black tea
79.9
White Tea
125
Bisabolol
160
Chamomile
320
Aloe Vera
535
Olive Leaf
675
PFE - purified feverfew extract
TNF-α ICD50 = conc req to achieve 50% inhibition of tumor necrosis factor-α Johson & Johnson, 2006
Tierney et al – 63rd Annual Meeting of the AAD – inhibition of UV Radiation induced erythema
Liebel et al, ADD Feb – demonstrated strong anti-inflammatory properties
Nebus et al ADD Feb – Significant improvement in erythema (n=31)

9. Glycyrrhiza- Licorice
Anti-bacteria
Anti-protozoan
Anti-tumor
Depigmentation
ANTI-INFLAMMATORY:
Razor Test
Shaved Skin
UV Induced Erythema Test
Hemoglobin reflectance
Cytokine production
Focus on Erythema, measure skin redness of shaven skin using reflectance spectroscopy
Anti-inflammatory efficacy of Licochalcone A
Kolbe et al Arch Dermatol Res (2008)

10. Hyperpigmentation Two Forms of Melanin produced in the Epidermis:
Pheomelanin
Eumelanin
Melanin Biosynthesis (melanogenesis)
Genetics
Environmental
Lifestyle
Medications
Production
Action of the Enzyme Tyrosinase
Copper
Oxygen
Sulfur
Hyper Pigmentation is a condition where the body produces too much melanin thereby causing to become darker than usual. Hyper pigmentation can occur due to excessive sun bathing or drug reactions. Many a time wounds and scars leave a darker patch of skin. Birthmarks, moles, and aging spots are also indications of hyper pigmentation. It is important to keep on the alert for any change in size, color or texture for indications of skin cancer.

Melanin biosynthesis (melanogenesis) is influenced by genetics, environmetal factors, diet and medication. The production of melanin by specialized cells called melanocytes (in the basal layer of the epidermis in light skinned people and in the basal as well as horney layer in dark skinned people) occures through the action of the enzyme tyrosinaase. The rate-limited step in melanogenesis is the conversaion of L0tyrosinase to melanin, through the action of tyrosinase. Copper and oxygen act as catalysts. Other enzymes also control melanin produciton, particularlry in the presense of sulfur.

11. Melanin Production Pathways

12. Transcription of the tyrosinase Gene
Melanin Production
Tyrosinase
Activated Tyrosinase
Melanin
Transcription of the tyrosinase Gene
Pigmentation pathway:
Tyrosinase Inhibition
Inhibition of melanin/melanos ome transport into keratinocytes
Increased Epidermal turnover
Glycosylation
+ sugar
Signals: UV
Irritation
Hormones
Radicals
Tyrosine
Varioation in skin pigmentation attributes to the levels of melanin produced and the number of melanocytes present.
Melanin granules synthesized in the melanocytes are then transferred from the cytoplasm of the melanocytes to the basal cytoplasm of the keratinocytes – Forming a protective covering in the inner layers of the epidermis, absorbing UV rays and inhibiting their penetration.
Melanin is packed into melanosomes
Keratinocytes

13. Melanin Production Pigmentation pathway: Tyrosinase Inhibition
Glycation
Inhibitors:
N-acetyl
glucosamine
Pigmentation pathway:
Tyrosinase Inhibition
Inhibition of melanin/melanos ome transport into keratinocytes
Increased Epidermal turnover
Gene production inhibitors:
retinoids
Tyrosinase
Activated Tyrosinane
Melanin
Transcription of the tyrosinase Gene
Signal Reduction:
Sunscreen, AA
Glycosylation
+ sugar
Signals: UV
Irritation
Hormones
Radicals
Tyrosine
Activity
Inhibitors:
Kojic Acid
Arbutin
Licorice
Varioation in skin pigmentation attributes to the levels of melanin produced and the number of melanocytes present.
Melanin granules synthesized in the melanocytes are then transferred from the cytoplasm of the melanocytes to the basal cytoplasm of the keratinocytes – Forming a protective covering in the inner layers of the epidermis, absorbing UV rays and inhibiting their penetration.
Melanin is packed into melanosomes
Melanosome Transfer Inhibition:
Niacinamide, Soy Protein
Keratinocytes

14. A review of the history Mechanism Ingredient Activity UV Absorption
Titanium dioxide, oxybenzone
Blocks UV
Tyrosinase synthesis inhibitor
Glucosamine, galactosamine
Exhibits cytotoxic effects
Tyronsinase Inhibitor
Ascorbic Acid, kojic acid, mulberry extract, licorice, arbutin, Curcuminoids
Melanin Biosynthesis
Kojic acid
Chelates copper ions
Cytotoxic effects to melanocytes
Hydroquinone
Safety Issues
Reduce preformed melanin
Tocopherols, ascorbic acid
Inhibits polymerization of melanin
Endothelin-1 inhibitor
Chamomilla extract
Erigeron breviscapus
Inhibits ET-1 induced DNA synthesis
Endothelin inhibitors are reported to work faster than tyronsinase inhibitors because their MOA is outside the melanocyte cell membrane. (Tyrosinase inhibitors have to crsoss four barriers for deactviation (stratum corneum, epidermis, melanocyte membrane and the melanosome membrane.
To discover an active skin depigmenting agent, we isolated a novel inhibitor of melanin biosynthesis from the methanol extract of Erigeron breviscapus using a bioactivity-guided fractionation and identified it as (2Z,8Z)-matricaria acid methyl ester by means of spectroscopic analysis. The compound showed strong whitening activity in melan-a cell. Compared with arbutin (IC(50)=4.0 mM) as a positive control, the depigmentation IC(50) value for (2Z,8Z)-matricaria acid methyl ester was 25.4 muM in B16F10 melanoma cell. Moreover, its inhibitory effect on tyrosinase, the key enzyme of melanogenesis, was examined by in vivo and in vitro tyrosinase assay and Western blot. The results indicate that (2Z,8Z)-matricaria acid methyl ester isolated from Erigeron breviscapus is a promising compound that could be useful for treating hyper-pigmentation as skin-whitening agents.

15. Active Soy Performance
Efficacy of Soy Moisturizer in PhotoAging, Wallo et al, JDD, Sept 2007

16. Erigeron breviscapus
Depigmentation of Melanocytes by Matricaria Acid Methyl Ester isolated from Erigeron breviscapus. Luo et al, Biol Pharm Bull 32(6) 2009

17. Combination Therapy Niacinamide & N-acetyl glucosamine
Reduction in the appearance of facial hyperpigmentation after use of moisturizer with combination
Of topical niacinamide and N-acetyl glucosamine: results of a randomized, double-blind study
Kimball et al., B J Dermatol, 2010, 162(2)

18. Combination Therapy Niacinamide & N-acetyl glucosamine
Reduction in the appearance of facial hyperpigmentation after use of moisturizer with combination
Of topical niacinamide and N-acetyl glucosamine: results of a randomized, double-blind study
Kimball et al., B J Dermatol, 2010, 162(2)

19. Combination Therapy Niacinamide & N-acetyl glucosamine
Dual Sites of Activation
N-acetyl glucosamine –
Inhibits Tyrosinase
Niacinamide –
Inhibits the transfer of melanin- containing melanosomes to the outer layers.

20. Inflammation+Hyperpigmentation: Combination therapies
Dr. Raval, MD Raval Facial Aesthetics, Rocky Mountain Laser Clinic, 2011
CDG = Glucarate 3 w/w%
GCA = Green Coffee Extract (50% CA) 3 w/w%
Combination CDG+GCA (3 w/w%)

21. Sunscreen Advances UVA / UVB Absorption Zinc Oxide / Titanium Dioxide
Photostabilizers –
Octocrylene
Avobenzone
Ecamsule
Antioxidants – Reduce ROS
Green Tea
Soy
Vitamin C

22. Pisum Sativum Extract
Pisum Sativum Extract for Safe & Self-tanning, Imbert et al Cosmetics & Toiletries
August, 2009 V124.