Combination of antioxidants, plant extract enhancing VDR synthesis and NB-UVB therapy for vitiligo skin care Katarzyna Równy Scientific Specialist @ dr Irena Eris Centre for Science and Research
Research approach 4 paths of investigation 1. Mitochondrial activation 2. IL-6 suppression 3. Silencing of Bmal1 and Per1 circadian genes 4. Antioxidative activity
Research approach 4 paths of investigation 1. Mitochondrial activation 2. IL-6 suppression 3. Silencing of Bmal1 and Per1 circadian genes 4. Antioxidative activity
Vitiligo and mitochondria we suggest that, in vitiligo, mitochondria might be the target of different stimuli, such as reactive oxygen species generation ( ) all of which are capable of inducing melanocyte degeneration Dell'Anna MLI et al. Mitochondrial impairment in peripheral blood mononuclear cells during the active phase of vitiligo. J Invest Dermatol. 2001 Oct; 117(4):908-13).
Mitochondrial potassium channels found in the inner mitochondrial membranes of various cells (neurons, myocardium) regulate mitochondrial membrane potential, respiration and synthesis of reactive oxygen species the activation is cytoprotective (open channels in myocardium heart attack rate )
Identification of mitok ATP channels in skin cells - PUBLICATIONS
IN VITRO STUDY Finding a substance modulating the activity of ATP-regulated potassium channel. screening 130 36 active ingredients to test
NARINGENIN flavonoid abundant in genus Citrus anti-oxidant, free radical scavenger anti-inflammatory anti-allergic
RESULTS ACTIVATION OF THE mitok ATP CHANNEL BY NARINGENIN UVA UVA + Naryngenin
RESULTS IN VITRO STUDIES NARINGENIN BENEFITS Regulatory effect in mitochondria membrane potential after UVA Regulatory effect on Ca 2+ level (with and w/o UVA) Reduction of ROS (with and w/o UVA) Induction of skin antioxidant defence system (MnSOD with and w/o UVA) Reduction in oxidative skin protein damages after UVA Protection of mitochondrial proteins against UVA Regulatory effect on mitochondrial biogenesis after UVA
Research approach 4 paths of investigation 1. Mitochondrial activation 2. IL-6 suppression 3. Silencing of Bmal1 and Per1 circadian genes 4. Antioxidative activity
Why IL-6? reported to play a role in immunological processes in vitiligo, can be an indicator of the disease in vitiligo patients level IL-6 in serum is 2x higher than in control patients reported to suppress melanocites proliferation Bellei B, Pitisci A, Ottaviani M, Ludovici M, Cota C, Luzi F, Dell'Anna ML, Picardo M. Vitiligo: a possible model of degenerative diseases. PLoS One. 2013;8(3):e59782. Moretti S, Fabbri P, Baroni G, Berti S, Bani D, Berti E, Nassini R, Lotti T, Massi D. Keratinocyte dysfunction in vitiligo epidermis: cytokine microenvironment and correlation to keratinocyte apoptosis. Histol Histopathol. 2009 Jul;24(7):849-57. Pastuszka M., Dermatologia Praktyczna, 2015, nr 5(40)
Viability [% of control] Reduction of IL-6 levels in cells - naringenin as IL-6 suppressor Viability and IL-6 levels in HaCaT cells with or w/o UVB radiation (30 mj/cm 2 ) IL-6 concentration [pg/ml] Control 0,001 0,01 0,033 [%] naringenin
IL-6 concentration [pg/ml] Reduction of IL-6 levels in cells - tioproline and rosmarinic acid synergistic IL-6 decreasing activity in keratinocytes (HaCaT) Rosmarinic Acid RA + tioproline 5mM RA + tioproline 7mM Patent application 19.02.2014, P. 407256 Rosmarinic Acid concentration [mg/l]
Research approach 4 paths of investigation 1. Mitochondrial activation 2. IL-6 suppression 3. Silencing Bmal1 and Per1 circadian genes 4. Antioxidative activity
Silencing of circadian genes Decreasing Bmal1 and Per1 activity Increased melanin production (activation of tyrosinase and MITF) Increased number of melanocyte dendrites UVB radiation decreases PER1 expression. ESDR, 2014 Carcidian genes activity reported in keratinocytes (Bmal1, PER1 - DNA repair).
Naringenin Per1 ans Bmal1 silencer
Research approach 4 paths of investigation 1. Mitochondrial activation 2. IL-6 suppression 3. Silencing of Bmal1 and Per1 circadian genes 4. Antioxidative activity
Antioxidative activity patented synergy tioproline and rosmarinic acid strong synergistic effect TioP (0,6 mg/ml) + RA (0,6 mg/ml) PATENT 17.12.2012, P. 402105 + 39,75% according to Hidalgo equation 2,47 according to Kull s equation
VDR vitamin D receptor and vitiligo VDR activator: increases synthesis of VDR in cells by 32% effect similar to calcitriol (active vit. D) Doss et al.: Vitamin D Receptor Expression in Vitiligo. Indian J Dermatol. 2015 Nov-Dec;60(6):544-8
VITI-MELO DAY VITI-MELO NIGHT PATENT 402105 TioP + RA ANTIOXIDANT ACTIVITY protects mitochondria from free radicals one of vitiligo triggers PATENT APPLICATION 407256 TioP + RA ANTI-INFLAMATORY ACTIVITY Minimizes melanocytes damage PATENT APPLICATION 416041 NARINGENIN silences the genes correlated to vitiligo symptoms and activates mitochondrial potassium channels
Antioxidative activity - THE EMULSIONS IN VITRO Product (index) RPF (10 21 DPPH/1g of emulsion) 1670 6,01 1671 4,19
CLINICAL STUDY in vivo evaluation of the efficacy of skin care products for vitiligo-affected skin
CLINICAL STUDY - materials and methods 38 patients with vitiligo use emulsion every evening for a period of 3 months 3 lesions per patient NB-UVB (311 nm) therapy only cream only combination of NB-UVB + cream 3 independent dermatological clinics: - evaluation of the localisation and area of vitiligo lesions in % VASI score (Vitiligo Area Scoring Index) 10-point analogues scale (skin elasticity and dryness) Patient s self-evaluation
CLINICAL STUDY - results NIGHT CREAM CLINICAL ASSESSMENT USING THE VITILIGO AREA SCORING INDEX (VASI) Patient assignment NB-UVB Night cream Night cream + NB-UVB Day 84 Improvment rates 5 out of 18 patients using light therapy (28% of test subjects) 3 out of 28 patients using the cream (11% of test subjects) 15 out of 28 patients using the cream in combination with light therapy (53% of test subjects) Average degree of repigmentation 11% Average degree of repigmentation 12.5% Average degree of repigmentation 30% (up to 70%)
CLINICAL STUDY - results The most spectacular improvement was observed when using the cream-gel for the night in combination with NB-UVB therapy. before after 3 months
CLINICAL STUDY - results NIGHT CREAM EFFECTIVENESS CONFIRMED BY CLINICAL TEST ON VITILIGO SKIN prevents the enlargement of white patches in 100% of test subjects 100% it moisturises the skin 78% nourishes the skin and replenishes lipids 63% regenerates the skin and restores its elasticity
CONCLUSIONS For the first time the mitok ATP were characterized in skin cells Naringenin acts as a modulator of mitok ATP in fibroblats Cosmetic products containing naringenin, tioproline and rosmarinic acid can safely and effectively restore vitiligious skin condition and enhance medical treatment with NB-UVB therapy. ACKNOWLEDGMENT This study was supported by a grant MERIS PBS1/B8/1/2012 from National Centre of Research and Development.
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