Colloidal Oatmeal (Avena Sativa) Improves Skin Barrier Through Multi-Therapy Activity.

Oats (Avena sativa) are a centuries-old topical treatment for a variety of skin barrier conditions, including dry skin, skin rashes, and eczema; however, few studies have investigated the actual mechanism of action for the skin barrier strengthening activity of colloidal oatmeal. Four extracts of colloidal oatmeal were prepared with various solvents and tested in vitro for skin barrier related gene expression and activity. Extracts of colloidal oatmeal were found to induce the expression of genes related to epidermal differentiation, tight junctions and lipid regulation in skin, and provide pH-buffering capacity. Colloidal oatmeal boosted the expression of multiple target genes related to skin barrier, and resulted in recovery of barrier damage in an in vitro model of atopic dermatitis. In addition, an investigator-blinded study was performed with 50 healthy female subjects who exhibited bilateral moderate to severe dry skin on their lower legs. Subjects were treated with a colloidal oatmeal skin protectant lotion. Clinically, the colloidal oatmeal lotion showed significant clinical improvements in skin dryness, moisturization, and barrier. Taken together, these results demonstrate that colloidal oatmeal can provide clinically effective benefits for dry and compromised skin by strengthening skin barrier.

J Drugs Dermatol. 2016;15(6):684-690.

Anti-inflammatory activities of colloidal oatmeal (Avena sativa) contribute to the effectiveness of oats in treatment of itch associated with dry, irritated skin.

BACKGROUND: Oat (Avena sativa) in colloidal form is a centuries-old topical treatment for a variety of skin conditions, including skin rashes, erythema, burns, itch, and eczema; however, few studies have investigated the exact mechanism of action for the anti-inflammatory activity of colloidal oatmeal. METHODS: Four extracts of colloidal oatmeal were made with various solvents and tested in anti-inflammatory and antioxidant assays. In addition, an investigator blind study was performed with twenty-nine healthy female subjects who exhibited bilateral mild to moderate itch with moderate to severe dry skin on their lower legs. Subjects were treated with a colloidal oatmeal skin protectant lotion. RESULTS: Extracts of colloidal oatmeal diminished pro-inflammatory cytokines in vitro and the colloidal oat skin protectant lotion showed significant clinical improvements in skin dryness, scaling, roughness, and itch intensity. CONCLUSIONS: These results demonstrate that colloidal oat extracts exhibit direct anti-oxidant and anti-inflammatory activities, which may provide the mechanisms for observed dermatological benefits while using the colloidal oatmeal skin protectant lotion.

Galvanic zinc-copper microparticles produce electrical stimulation that reduces the inflammatory and immune responses in skin.

The human body has its own innate electrical system that regulates the body's functions via communications among organs through the well-known neural system. While the effect of low-level electrical stimulation on wound repair has been reported, few studies have examined the effect of electric potential on non-wounded, intact skin. A galvanic couple comprised of elemental zinc and copper was used to determine the effects of low-level electrical stimulation on intact skin physiology using a Dermacorder device. Zn-Cu induced the electrical potential recorded on intact skin, enhanced H(2)O(2) production and activated p38 MAPK and Hsp27 in primary keratinocytes. Treatment with Zn-Cu was also found to reduce pro-inflammatory cytokines, such as IL-1α, IL-2, NO and TNF-α in multiple cell types after stimulation with PHA or Propionibacterium acnes bacteria. The Zn-Cu complex led to a dose-dependent inhibition of TNF-α-induced NF-κB levels in keratinocytes as measured by a dual-luciferase promoter assay, and prevented p65 translocation to the nucleus observed via immunofluorescence. Suppression of NF-κB activity via crosstalk with p38 MAPK might be one of the potential pathways by which Zn-Cu exerted its inflammatory effects. Topical application of Zn-Cu successfully mitigated TPA-induced dermatitis and oxazolone-induced hypersensitivity in mice models of ear edema. Anti-inflammatory activity induced by the Zn-Cu galvanic couple appears to be mediated, at least in part, by production of low level of hydrogen peroxide since this activity is reversed by the addition of Catalase enzyme. Collectively, these results show that a galvanic couple containing Zn-Cu strongly reduces the inflammatory and immune responses in intact skin, providing evidence for the role of electric stimulation in non-wounded skin.

The StrataTest® human skin model, a consistent in vitro alternative for toxicological testing.

Three-dimensional in vitro skin models provide an alternative to animal testing for assessing tissue damage caused by chemical or physical agents and for the identification and characterization of agents formulated to mitigate this damage. The StrataTest® human skin model made with pathogen-free NIKS® keratinocyte progenitors is a fully-stratified tissue containing epidermal and dermal components that possesses barrier function as determined by measurements of electrical impedance. Independent batches of skin tissues responded consistently to known chemical irritants even after refrigerated storage for up to 7 days. Reactive oxygen species (ROS) were detected after exposure of skin tissues to ozone, cigarette smoke or ultraviolet (UV) irradiation. Pretreatment with the antioxidant parthenolide-depleted (PD)-Feverfew extract prevented cigarette smoke-induced or UV irradiation-mediated increases in ROS. Interleukin (IL)-1α and IL-1 receptor antagonist (IL-1RA) secretion increased in a dose dependent manner following UV irradiation but cytokine release was abrogated by pretreatment with a UVA/UVB sunscreen. Similarly, immunohistochemical detection showed increased thymidine dimer formation in UV-irradiated skin tissue that was prevented with sunscreen pretreatment. These results demonstrate that the StrataTest® human skin model is broadly applicable to a wide range of in vitro toxicological assays.

Parthenolide-depleted Feverfew (Tanacetum parthenium) protects skin from UV irradiation and external aggression.

The skin is under continual assault from a variety of damaging environmental factors such as ultraviolet irradiation and atmospheric pollutants, and as organisms age the cumulative damage exceeds the capacity of endogenous antioxidant defenses resulting in chronic inflammation and premature aging. Botanical extracts such as Feverfew containing naturally occurring antioxidants could replenish the depleted cutaneous stores and perhaps forestall these degenerative changes. A parthenolide-depleted extract of Feverfew (PD-Feverfew), which was free of sensitization potential, was found to possess free radical scavenging activity against a wide range of reactive oxygen species and with greater activity than Vitamin C. In vitro, PD-Feverfew restored cigarette smoke-mediated depletion of cellular thiols, attenuated the formation of UV-induced hydrogen peroxide and reduced pro-inflammatory cytokine release. In vivo, topical PD-Feverfew reduced UV-induced epidermal hyperplasia, DNA damage and apoptosis. In a clinical study PD-Feverfew treatment significantly reduced erythema versus placebo 24 h post-UV exposure. Through the ability to scavenge free radicals, preserve endogenous antioxidant levels, reduce DNA damage and induce DNA repair enzymes, which can help repair damaged DNA, parthenolide-depleted extract of Feverfew may protect skin from the numerous external aggressions encountered daily by the skin and reduce the damage to oxidatively challenged skin.

Anti-inflammatory activity of sertaconazole nitrate is mediated via activation of a p38-COX-2-PGE2 pathway.

Sertaconazole nitrate is an antifungal agent that exhibits anti-inflammatory activity; however, the mechanism for this action was unknown. We investigated the cellular mechanisms by which sertaconazole exerts its anti-inflammatory activity in keratinocytes and human peripheral blood mononuclear cells (PBMCs). Paradoxically, sertaconazole was found to activate the proinflammatory p38 mitogen-activated protein kinase. Treatment with sertaconazole also resulted in the induction of cyclooxygenase-2 (COX-2) and the subsequent release of prostaglandin E2 (PGE2). Knocking down p38 in keratinocytes using small interfering RNA resulted in an inhibition of sertaconazole-induced PGE2 release confirming that activation of p38 was required for PGE2 production. Additionally, in stimulated keratinocytes and human PBMCs, sertaconazole was found to suppress the release of cytokines. Treatment with anti-PGE2 antiserum or the COX-2 inhibitor NS398 reversed the inhibitory effects of sertaconazole on the release of proinflammatory cytokines, linking endogenous PGE2 with the anti-inflammatory effects. Finally, in an in vivo mouse model of tetradecanoyl phorbol acetate (TPA)-induced dermatitis, the sertaconazole-mediated inhibition of TPA-induced ear edema was reversed by NS398. Biochemical analysis of tissue biopsies revealed increase in PGE2 levels in sertaconazole-treated mice. Thus, activation of the p38-COX-2-PGE2 pathway by agents such as sertaconazole provides anti-inflammatory therapeutic benefits.

Anti-inflammatory and anti-itch activity of sertaconazole nitrate.

Cutaneous fungal infections are frequently associated with an inflammatory component including irritated skin, itching and stinging/burning. Therapeutic anti-fungal agents that have anti-inflammatory activity have the potential to provide clinical benefit beyond fungus eradication. Recently, certain anti-fungal agents have been shown to have intrinsic anti-inflammatory activity, therefore we sought to determine the extent of the anti-inflammatory activity of these compounds. The anti-inflammatory activities of eight anti-fungal agents (butoconazole, ciclopirox olamine, fluconazole, miconazole nitrate, sertaconazole nitrate, terconazole, tioconazole and ketoconazole) were compared in a number of preclinical models of dermal inflammation and pruritus. While butoconazole, ciclopirox olamine, fluconazole, and miconazole nitrate were all found to have anti-inflammatory activity, only sertaconazole nitrate reduced the release of cytokines from activated lymphocytes and mitigated inflammation in animal models of irritant contact dermatitis and neurogenic inflammation. In addition, sertaconazole nitrate inhibited contact hypersensitivity and scratching responses in a murine model of pruritus. Furthermore, the in vitro and in vivo anti-inflammatory activity of sertaconazole nitrate was found to be greater than other topical anti-fungal agents examined. These studies demonstrate that topical administration of clinically relevant concentrations of sertaconazole nitrate resulted in an efficacious anti-inflammatory activity against a broad spectrum of dermal inflammation models and itch. The anti-inflammatory properties of sertaconazole may contribute to the efficacy of the drug in the treatment of cutaneous fungal conditions and provide greater anti-inflammatory activity compared with other anti-fungal agents.

Differential regulation of HIF-1 alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells.

Three HIF-alpha prolyl-4-hydroxylases (PHDs) (named PHD1, PHD2, and PHD3) effect the proteasome-mediated degradation of HIF by catalyzing the hydroxylation of key proline residues in the HIF-1 alpha subunit under normoxic conditions. When oxygen tension is reduced, PHD-mediated hydroxylation cannot occur, HIF-1 alpha accumulates in the nucleus, resulting in HIF-mediated gene transcription. In the present study, the expression and regulation of PHD mRNA and HIF protein expression was examined in human tissues and primary cells of cardiovascular origin. Treatment of human cardiac myocytes, smooth muscle cells, and endothelial cells with hypoxia or CoCl(2), a hypoxia mimic, resulted in a significant time-dependent increase in PHD3, but not PHD1 or PHD2, mRNA levels, which correlated with an increase in HIF-1 alpha protein expression. Overexpression studies revealed that PHD3 levels influence HIF-1 alpha stability in both normoxic and hypoxic conditions, suggesting that PHD3 may participate in a feedback loop controlling HIF activity.