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Fernandez J.R.,Signum Dermalogix | Rouzard K.,Signum Dermalogix | Voronkov M.,Signum Dermalogix | Huber K.L.,Signum Dermalogix | And 5 more authors.
Journal of Cosmetic Dermatology | Year: 2016

Background: Isoprenylcysteine (IPC) small molecules were identified as a new class of anti-inflammatory compounds over 20 years ago. Since then, they have been developed as novel cosmetic functional ingredients (CFI) and topical drug candidates. SIG1273 is a second generation CFI that has previously been shown to provide a broad spectrum of benefits for the skin through its anti-inflammatory and antimicrobial properties. Objective: To determine whether SIG1273 possesses anti-aging properties in vitro and evaluate the tolerability and activity of SIG1273 when applied topically to human subjects. Methods: To model photoaging in vitro, human dermal fibroblasts (HDFs) were exposed in culture to UVA to induce collagenase (MMP-1) production. An in vitro wound-healing model was based on the activation of HDF migration into cell-free tissue culture surface. Hydrogen peroxide-induced oxidative stress was performed using HDFs to measure intracellular ROS activity. Radical scavenging capacity was determined using a colorimetric antioxidant assay kit (ABTS method). Lastly, a 4-week, 29-subject study was performed in which SIG1273 was applied topically as a cream to assess its tolerance and activity in reducing the appearance of aging. Results: In vitro studies demonstrate SIG1273 inhibits UVA-induced MMP-1 production, hydrogen peroxide-induced oxidative stress and promotes wound healing. Moreover, SIG1273 was shown to be a radical scavenging antioxidant. Clinical assessment of SIG1273 cream (0.25%) showed it was well tolerated with significant improvement in the appearance of fine lines, coarse wrinkles, radiance/luminosity, pore size, texture/smoothness, hydration and increased firmness. Conclusions: SIG1273 represents a novel CFI with antioxidant, anti-aging, and anti-inflammatory properties that when applied topically is well tolerated and provides benefits to individuals with aging skin. © 2016 Wiley Periodicals, Inc. Source


Fernandez J.R.,Signum Dermalogix | Rouzard K.,Signum Dermalogix | Voronkov M.,Signum Dermalogix | Huber K.L.,Signum Dermalogix | And 4 more authors.
International Journal of Cosmetic Science | Year: 2015

Synopsis Background The skin is the first line of defence against exposure to microbial, physical, environmental and chemical insults. In mobilizing a protective response, several different cell types located in our skin release and respond to pro-inflammatory cytokines ensuring skin homeostasis and health. However, chronic activation of this response eventually causes damage resulting in premature ageing. Diosodium tetramethylhexadecenyl succinyl cysteine (TSC or SIG1273), an isoprenylcysteine small molecule, down modulates these inflammatory signalling pathways in various cell types (keratinocytes, peripheral blood mononuclear cells (PBMCs) and endothelial cells) and possesses anti-bacterial properties. Thus, TSC represents a novel cosmetic functional ingredient that provides a broad spectrum of benefits for the skin. Objective To assess the anti-inflammatory properties of TSC in several cutaneous cell types and further investigate its anti-microbial activity. Methods Cultured normal human epidermal keratinocytes were exposed to chemical irritant phorbol 12-myrisate 13-acetate (TPA) or ultraviolet-B light (UVB) to induce pro-inflammatory cytokine (IL-6, IL-8 and TNF-α) production. T-cell receptor (TCR) activation of PBMCs and nickel (Ni2+) treatments of human dermal microvascular endothelial cells (HDMECs) were performed resulting in IL-4, IL-6, IL-8 and IL-17 production. Streptococcus pyogenes were cultured to determine minimal inhibitory concentration values. Results In vitro studies demonstrate TSC blocks TPA and UVB-induced cytokine production in cultured keratinocytes. Similarly, TSC inhibits overproduction of IL-4 and IL-17 in T-cell receptor (TCR)-activated PBMCs as well as nickel induction of IL-6 and IL-8 in HDMECs. Lastly, TSC demonstrated anti-microbial properties, inhibiting cell growth of S. pyogenes. Conclusions Tetramethylhexadecenyl succinyl cysteine represents a novel cosmetic functional ingredient that provides a dual modulating benefit of skin protection to individuals by reducing inflammation in keratinocytes, endothelial and mononuclear cell types and S. pyogenes counts. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie. Source


Fernandez J.R.,Signum Dermalogix | Fernandez J.R.,Signum Biosciences | Rouzard K.,Signum Dermalogix | Rouzard K.,Signum Biosciences | And 12 more authors.
Journal of Cosmetic Dermatology | Year: 2012

Background: Propionibacterium acnes is a major contributing factor to the inflammatory component of acne. The interaction of P. acnes with keratinocytes leads to an innate immune response via activation of toll-like receptors (TLR2, TLR4) resulting in the production and secretion of pro-inflammatory mediators. SIG1273, an isoprenylcysteine small molecule modulates inflammatory signaling pathways and kills P. acnes. SIG1273 represents a novel cosmetic functional ingredient that provides relief from blemishes in acne prone skin. Objective: To assess the keratinocyte response and microbial growth of SIG1273 in vitro and evaluate the tolerability of SIG1273 gel applied topically in acne prone subjects. Methods: For in vitro studies, human keratinocytes were exposed in culture to live P. acnes and peptidoglycan (PGN) to induce IL-8 production. P. acnes were cultured to determine minimal inhibitory concentration and minimal bactericidal concentration values. A total of 30 subjects were randomized in a double-blind controlled trial receiving 3% SIG1273 gel or vehicle for 6 weeks. Evaluation included inflammatory lesions, noninflammatory lesions, microcomedones, Sebutape scores, and P. acnes counts. Results: In vitro studies demonstrate SIG1273 inhibits P. acnes-induced IL-8 production and inhibits P. acnes growth. SIG1273 gel was well tolerated with no signs of stinging, redness, or itching. Furthermore, improvement in some aspects of acne was observed in subjects applying SIG1273 gel, including inflammatory lesions, microcomedone counts and Sebutape scores. Facial scrubs taken to measure P. acnes colony-forming units showed those applying SIG1273 gel had ~1.0 Log 10 colony reduction over the length of the study, a statistically significantly improvement when compared with vehicle. No significant effects above vehicle were observed for noninflammatory lesions. Conclusions: SIG1273 represents a novel cosmetic functional ingredient that provides a safe dual modulating benefit to individuals with acne prone skin by reducing P. acnes counts and reducing inflammation. © 2012 Wiley Periodicals, Inc. Source

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