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1.
J Cosmet Dermatol ; 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38525606

ABSTRACT

BACKGROUND: Tetrahexydecyl ascorbate (THDA) is a lipophilic precursor to ascorbic acid that may be stabilized by acetyl zingerone (AZ). Studies have shown that the topical application of THDA may have photoprotective effects. Similarly, AZ has been shown to mitigate oxidative and inflammatory stress, thereby improving the appearance of photoaging. AIMS: To examine the effects of THDA and AZ (THDA-AZ) on skin photoaging compared to THDA alone. PATIENTS/METHODS: In this double-blind, randomized controlled trial, healthy individuals aged 30 to 65 were included and 44 participants were randomized to receive either THDA-AZ (THDA 5% + AZ 1%) or THDA only (THDA 5%) for 8 weeks. Facial photographs were taken at 0, 4, and 8 weeks to analyze wrinkle severity, pigment intensity, and redness intensity. A skin colorimeter was used to assess infraorbital pigmentation and erythema. Self-perception of skin and tolerability were assessed through questionnaires. RESULTS: Average wrinkle severity was significantly decreased in the THDA-AZ group at Weeks 4 and 8 by 0.75% (p = 0.023) and 3.72% (p = 0.048), respectively, compared to the THDA group where wrinkle severity at Weeks 4 and 8 was increased by 7.88% and 4.48%, respectively. Facial pigment intensity was significantly decreased in the THDA-AZ group by 4.10% (p = 0.0002) at Week 8 compared to a 0.69% decrease in the THDA group. Facial redness intensity was decreased in the THDA-AZ group at Weeks 4 and 8 by 3.73% (p = 0.0162) and 14.25% (p = 0.045), respectively, compared to the THDA group where at Weeks 4 and 8 erythema increased by 27.5% and 8.34%, respectively. There were no significant differences in either group for infraorbital pigmentation or erythema. CONCLUSIONS: Daily use of combined THDA and AZ may improve facial wrinkle severity, pigment intensity, and erythema to a greater extent than THDA. While THDA alone increases facial wrinkle severity and erythema, the addition of AZ reduces both.

2.
Dermatitis ; 35(S1): S62-S69, 2024.
Article in English | MEDLINE | ID: mdl-38394048

ABSTRACT

Background: Preliminary studies support the use of topical coconut and sunflower seed oil for atopic dermatitis (AD). However, standardized topical formulations of fatty acids from these sources have not been studied. Objective: This study investigates whether coconut oil- and sunflower seed oil-derived isosorbide diesters can be used in conjunction with colloidal oatmeal to improve itch, AD severity, and the need for topical steroids in adults. Methods: This was a single-center, 4-week, randomized, double-blind, and vehicle-controlled study conducted between 2021 and 2022. Thirty-two male and female adults with mild-to-moderate AD were enrolled and completed the study. Participants were randomized to receive either 0.1% colloidal oatmeal (vehicle) or isosorbide diesters (IDEAS, 4% isosorbide dicaprylate and 4% isosorbide disunflowerseedate) along with 0.1% colloidal oatmeal. The main outcomes of the study were changes in the visual analogue rating of itch and 75% improvement in the Eczema Area and Severity Index score (EASI 75) at 4 weeks. Other measures included the use of topical steroids and the relative abundance of skin Staphylococcus aureus. Results: Participants in the IDEAS group had a 65.6% improvement in itch compared with 43.8% in the vehicle group (P = 0.013). In total, 56.5% and 25% of the those in the IDEAS and vehicle groups, respectively, achieved EASI 75 at 4 weeks (P = 0.07). There was no difference in skin hydration or transepidermal water loss. The relative abundance of S. aureus was decreased in the IDEAS group at week 4 compared with no change in the vehicle group (P = 0.044). Topical corticosteroid use increased in the vehicle group compared with a decrease in the IDEAS group at week 1 (292.5% vs 24.8%; P value = 0.039) and week 2 (220% vs 46%; P value = 0.08). Conclusions: Topical application of emollients containing coconut oil- and sunflower seed oil-derived fatty esters may improve itch, reduce topical steroid use, and reduce the relative abundance of S. aureus in mild-to-moderate AD. CTR number: NCT04831892.


Subject(s)
Dermatitis, Atopic , Adult , Humans , Male , Female , Dermatitis, Atopic/drug therapy , Sunflower Oil , Coconut Oil , Staphylococcus aureus , Cocos , Prospective Studies , Treatment Outcome , Pruritus/drug therapy , Emollients , Double-Blind Method , Severity of Illness Index , Steroids
3.
Antioxidants (Basel) ; 12(6)2023 May 29.
Article in English | MEDLINE | ID: mdl-37371898

ABSTRACT

The cumulative damage skin sustains from exposure to environmental stressors throughout life exerts significant effects on skin aging and cancer development. One of the main ways by which environmental stressors mediate their effects within skin is through induction of reactive oxygen species (ROS). In this review, we chronicle the multiple properties by which acetyl zingerone (AZ) as a skincare ingredient can benefit skin (1) by helping manage overproduction of ROS through multiple routes as an antioxidant, physical quencher and selective chelator, (2) by fortifying protection after UV exposure ends to prevent the type of epidermal DNA damage that correlates with development of skin cancer, (3) by modulating matrisome activity and nurturing the integrity of the extracellular matrix (ECM) within the dermis and (4) through its proficient ability to neutralize singlet oxygen, by stabilizing the ascorbic acid precursor tetrahexyldecyl ascorbate (THDC) in the dermal microenvironment. This activity improves THDC bioavailability and may blunt pro-inflammatory effects of THDC, such as activation of type I interferon signaling. Moreover, AZ is photostable and can sustain its properties during UV exposure, in contrast to α-tocopherol. All these properties of AZ translate into measurable clinical benefits to improve the visual appearance of photoaged facial skin and to strengthen the skin's own defenses against sun damage.

4.
JID Innov ; 3(3): 100178, 2023 May.
Article in English | MEDLINE | ID: mdl-36992949

ABSTRACT

The endocannabinoid (eCB) system plays an active role in epidermal homeostasis. Phytocannabinoids such as cannabidiol modulate this system but also act through eCB-independent mechanisms. This study evaluated the effects of cannabidiol, bakuchiol (BAK), and ethyl (linoleate/oleate) (ELN) in keratinocytes and reconstituted human epidermis. Molecular docking simulations showed that each compound binds the active site of the eCB carrier FABP5. However, BAK and ethyl linoleate bound this site with the highest affinity when combined 1:1 (w/w), and in vitro assays showed that BAK + ELN most effectively inhibited FABP5 and fatty acid amide hydrolase. In TNF-stimulated keratinocytes, BAK + ELN reversed TNF-induced expression shifts and uniquely downregulated type I IFN genes and PTGS2 (COX2). BAK + ELN also repressed expression of genes linked to keratinocyte differentiation but upregulated those associated with proliferation. Finally, BAK + ELN inhibited cortisol secretion in reconstituted human epidermis skin (not observed with cannabidiol). These results support a model in which BAK and ELN synergistically interact to inhibit eCB degradation, favoring eCB mobilization and inhibition of downstream inflammatory mediators (e.g., TNF, COX-2, type I IFN). A topical combination of these ingredients may thus enhance cutaneous eCB tone or potentiate other modulators, suggesting novel ways to modulate the eCB system for innovative skincare product development.

5.
J Clin Med ; 12(4)2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36836126

ABSTRACT

Terminalia chebula (TC) is a medicinal plant that exhibits antioxidant, anti-inflammatory, and antibacterial properties and that is widely used in Ayurveda and herbal formulations. However, the skin effects of TC as an oral supplement have not been studied. The objective of this study is to determine if oral TC fruit extract supplementation can modulate the skin's sebum production and reduce the appearance of wrinkles. A prospective double-blind placebo-controlled study was conducted on healthy females aged 25-65. Subjects were supplemented with an oral placebo or Terminalia chebula (250 mg capsule, Synastol TC) capsules twice daily for eight weeks. A facial image collection and analysis system was used to assess the facial appearance of wrinkle severity. Standardized, non-invasive tools were used to measure facial moisture, sebum production, transepidermal water loss, melanin index and erythema index. For those who had a baseline sebum excretion rate >80 ug/cm2, TC supplementation produced a significant decrease in forehead sebum excretion rate compared to the placebo at four weeks (-17 decrease vs. 20% increase, p = 0.07) and at eight weeks (-33% decrease vs. 29% increase, p < 0.01). Cheek erythema decreased by 2.2% at eight weeks, while the placebo treatment increased cheek erythema by 1.5% (p < 0.05). Facial wrinkles decreased by 4.3% in the TC group and increased by 3.9% in the placebo group after eight weeks of supplementation (p < 0.05). TC supplementation reduces facial sebum and improves the appearance of wrinkles. Future studies should consider evaluating oral TC as adjuvant therapy for acne vulgaris.

6.
Antioxidants (Basel) ; 12(2)2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36829837

ABSTRACT

Cyclobutane pyrimidine dimers (CPDs) are ultraviolet radiation (UV)-induced carcinogenic DNA photoproducts that lead to UV signature mutations in melanoma. Previously, we discovered that, in addition to their incident formation (iCPDs), UV exposure induces melanin chemiexcitation (MeCh), where UV generates peroxynitrite (ONOO-), which oxidizes melanin into melanin-carbonyls (MCs) in their excited triplet state. Chronic MeCh and energy transfer by MCs to DNA generates CPDs for several hours after UV exposure ends (dark CPD, dCPDs). We hypothesized that MeCh and the resulting dCPDs can be inhibited using MeCh inhibitors, and MC and ONOO- scavengers. Here, we investigated the efficacy of Acetyl Zingerone (AZ), a plant-based phenolic alkanone, and its chemical analogs in inhibiting iCPDs and dCPDs in skin fibroblasts, keratinocytes, and isogenic pigmented and albino melanocytes. While AZ and its methoxy analog, 3-(4-Methoxy-benzyl)-Pentane-2,4-dione (MBPD) completely inhibited the dCPDs, MBPD also inhibited ~50% of iCPDs. This suggests the inhibition of ~80% of total CPDs at any time point post UV exposure by MBPD, which is markedly significant. MBPD downregulated melanin synthesis, which is indispensable for dCPD generation, but this did not occur with AZ. Meanwhile, AZ and MBPD both upregulated the expression of nucleotide excision repair (NER) pathways genes including Xpa, Xpc, and Mitf. AZ and its analogs were non-toxic to the skin cells and did not act as photosensitizers. We propose that AZ and MBPD represent "next-generation skin care additives" that are safe and effective for use not only in sunscreens but also in other specialized clinical applications owing to their extremely high efficacy in blocking both iCPDs and dCPDs.

7.
Int J Mol Sci ; 23(22)2022 Nov 18.
Article in English | MEDLINE | ID: mdl-36430783

ABSTRACT

Atopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (IDL) and isosorbide dicaprylate (IDC), using AD-like tissue culture models. Treatment of reconstituted human epidermis with cytokine cocktail (IL-4 + IL-13 + TNF-α + IL-31) compromised the epidermal barrier, but this was prevented by co-treatment with IDL and IDC. Cytokine stimulation also dysregulated expression of keratinocyte (KC) differentiation genes whereas treatment with IDC or IDL + IDC up-regulated genes associated with early (but not late) KC differentiation. Although neither IDL nor IDC inhibited Th2 cytokine responses, both compounds repressed TNF-α-induced genes and IDL + IDC led to synergistic down-regulation of inflammatory (IL1B, ITGA5) and neurogenic pruritus (TRPA1) mediators. Treatment of cytokine-stimulated skin explants with IDC decreased lactate dehydrogenase (LDH) secretion by more than 50% (more than observed with cyclosporine) and in vitro LDH activity was inhibited by IDL and IDC. These results demonstrate anti-inflammatory mechanisms of isosorbide fatty acid diesters in AD-like skin models. Our findings highlight the multifunctional potential of plant oil derivatives as topical ingredients and support studies of IDL and IDC as therapeutic candidates.


Subject(s)
Dermatitis, Atopic , Humans , Dermatitis, Atopic/drug therapy , Cytokines , Fatty Acids , Isosorbide , Tumor Necrosis Factor-alpha/pharmacology , Plant Oils , Oleic Acid
8.
Pharmaceuticals (Basel) ; 15(4)2022 Apr 11.
Article in English | MEDLINE | ID: mdl-35455458

ABSTRACT

Dimethyl fumarate (DMF) has emerged as a first-line therapy for relapsing-remitting multiple sclerosis (RRMS). This treatment, however, has been limited by adverse effects, which has prompted development of novel derivatives with improved tolerability. We compared the effects of fumarates on gene expression in astrocytes. Our analysis included diroximel fumarate (DRF) and its metabolite monomethyl fumarate (MMF), along with a novel compound isosorbide di-(methyl fumarate) (IDMF). Treatment with IDMF resulted in the largest number of differentially expressed genes. The effects of DRF and MMF were consistent with NRF2 activation and NF-κB inhibition, respectively. IDMF responses, however, were concordant with both NRF2 activation and NF-κB inhibition, and we confirmed IDMF-mediated NF-κB inhibition using a reporter assay. IDMF also down-regulated IRF1 expression and IDMF-decreased gene promoters were enriched with IRF1 recognition sequences. Genes altered by each fumarate overlapped significantly with those near loci from MS genetic association studies, but IDMF had the strongest overall effect on MS-associated genes. These results show that next-generation fumarates, such as DRF and IDMF, have effects differing from those of the MMF metabolite. Our findings support a model in which IDMF attenuates oxidative stress via NRF2 activation, with suppression of NF-κB and IRF1 contributing to mitigation of inflammation and pyroptosis.

9.
JID Innov ; 1(4): 100040, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34909741

ABSTRACT

Dimethyl fumarate (DMF) is an effective oral treatment for psoriasis administered in Europe for nearly 60 years. However, its potential has been limited by contact dermatitis that prohibits topical application. This paper characterizes a DMF derivative, isosorbide DMF (IDMF), which was designed to have antipsoriatic effects without skin-sensitizing properties. We show that IDMF exhibits neither genotoxicity nor radiation sensitivity in skin fibroblasts and is nonirritating and nonsensitizing in animal models (rat, rabbit, guinea pig). Microarray analysis of cytokine-stimulated keratinocytes showed that IDMF represses the expression of genes specifically upregulated in psoriatic skin lesions but not those of other skin diseases. IDMF also downregulated genes induced by IL-17A and TNF in keratinocytes as well as predicted targets of NF-κB and the antidifferentiation noncoding RNA (i.e., ANCR). IDMF further stimulated the transcription of oxidative stress response genes (NQO1, GPX2, GSR) with stronger NRF2/ARE activation compared to DMF. Finally, IDMF reduced erythema and scaling while repressing the expression of immune response genes in psoriasiform lesions elicited by topical application of imiquimod in mice. These data show that IDMF exhibits antipsoriatic activity that is similar or improved compared with that exhibited by DMF, without the harsh skin-sensitizing effects that have prevented topical delivery of the parent molecule.

10.
Clin Cosmet Investig Dermatol ; 14: 1257-1269, 2021.
Article in English | MEDLINE | ID: mdl-34557011

ABSTRACT

BACKGROUND: Identification of long-lasting natural antioxidants to protect against and repair skin damage induced by exposure to environmental pollution is in high demand. OBJECTIVE: To investigate a standardized Terminalia chebula (TC) fruit extract for its long-lasting antioxidant and anti-inflammatory properties and its ability to reverse the visible signs of pollution-induced skin damage in an 8-week clinical study. MATERIAL AND METHODS: Chemical and cell-based in vitro studies were performed to characterize long-lasting antioxidant and anti-inflammatory properties; a clinical study with subjects with normal to dry skin living in a high-pollution city for the previous 5 years was conducted to assess if a formulation containing 1% standardized TC fruit extract affected significant improvements in skin's visible condition and appearance compared with its placebo. RESULTS: The standardized TC fruit extract provided longer-lasting and more efficient neutralization of reactive oxygen species (ROS) than tocopherol; treatment of keratinocytes with the fruit extract prior to being stressed with urban dust safeguarded against increases in intracellular ROS, inhibited release of inflammatory cytokines IL-6 and IL-8 and protected membrane lipids against peroxidation. A clinical study yielded statistically significant improvements in dermatologist scores and subject self-assessments for skin texture, hydration, tone, firmness and radiance as compared to its placebo. CONCLUSION: These studies validate the use of this standardized TC fruit extract not only as a restorative to diminish visible signs of existing damage but also as a preventative to help defend skin against damages caused by chronic exposure to environmental pollution.

11.
Int J Mol Sci ; 22(16)2021 Aug 15.
Article in English | MEDLINE | ID: mdl-34445461

ABSTRACT

Tetrahexyldecyl Ascorbate (THDC) is an L-ascorbic acid precursor with improved stability and ability to penetrate the epidermis. The stability and transdermal penetration of THDC, however, may be compromised by the oxidant-rich environment of human skin. In this study, we show that THDC is a poor antioxidant that degrades rapidly when exposed to singlet oxygen. This degradation, however, was prevented by combination with acetyl zingerone (AZ) as a stabilizing antioxidant. As a standalone ingredient, THDC led to unexpected activation of type I interferon signaling, but this pro-inflammatory effect was blunted in the presence of AZ. Moreover, the combination of THDC and AZ increased expression of genes associated with phospholipid homeostasis and keratinocyte differentiation, along with repression of MMP1 and MMP7 expression, inhibition of MMP enzyme activity, and increased production of collagen proteins by dermal fibroblasts. Lastly, whereas THDC alone reduced viability of keratinocytes exposed to oxidative stress, this effect was completely abrogated by the addition of AZ to THDC. These results show that AZ is an effective antioxidant stabilizer of THDC and that combination of these products may improve ascorbic acid delivery. This provides a step towards reaching the full potential of ascorbate as an active ingredient in topical preparations.


Subject(s)
Antioxidants , Ascorbic Acid , Collagen/biosynthesis , Fibroblasts/metabolism , Guaiacol/analogs & derivatives , Oxidative Stress/drug effects , Antioxidants/pharmacokinetics , Antioxidants/pharmacology , Ascorbic Acid/pharmacokinetics , Ascorbic Acid/pharmacology , Cell Line , Guaiacol/pharmacokinetics , Guaiacol/pharmacology , Humans
12.
J Invest Dermatol ; 141(6): 1416-1427.e12, 2021 06.
Article in English | MEDLINE | ID: mdl-33181142

ABSTRACT

The breakdown of the epidermal barrier and consequent loss of skin hydration is a feature of skin aging and eczematous dermatitis. Few treatments, however, resolve these underlying processes to provide full symptomatic relief. In this study, we evaluated isosorbide di-(linoleate/oleate) (IDL), which was generated by esterifying isosorbide with sunflower fatty acids. Topical effects of IDL in skin were compared with those of ethyl linoleate/oleate, which has previously been shown to improve skin barrier function. Both IDL and ethyl linoleate/oleate downregulated inflammatory gene expression, but IDL more effectively upregulated the expression of genes associated with keratinocyte differentiation (e.g., KRT1, GRHL2, SPRR4). Consistent with this, IDL increased the abundance of epidermal barrier proteins (FLG and involucrin) and prevented cytokine-mediated stratum corneum degradation. IDL also downregulated the expression of unhealthy skin signature genes linked to the loss of epidermal homeostasis and uniquely repressed an IFN-inducible coexpression module activated in multiple skin diseases, including psoriasis. In a double-blind, placebo-controlled trial enrolling females with dry skin, 2% IDL lotion applied over 2 weeks significantly improved skin hydration and decreased transepidermal water loss (NCT04253704). These results demonstrate mechanisms by which IDL improves skin hydration and epidermal barrier function, supporting IDL as an effective intervention for the treatment of xerotic pruritic skin.


Subject(s)
Dermatitis, Atopic/drug therapy , Emollients/administration & dosage , Keratinocytes/drug effects , Skin Cream/administration & dosage , Water Loss, Insensible/drug effects , Adult , Cell Differentiation/drug effects , Cell Differentiation/genetics , Dermatitis, Atopic/pathology , Double-Blind Method , Emollients/adverse effects , Emollients/chemistry , Epidermis/drug effects , Epidermis/pathology , Female , Filaggrin Proteins , Follow-Up Studies , Gene Expression Profiling , Gene Expression Regulation/drug effects , Humans , Isosorbide/administration & dosage , Isosorbide/adverse effects , Isosorbide/chemistry , Keratinocytes/pathology , Linoleic Acid/administration & dosage , Linoleic Acid/adverse effects , Linoleic Acid/chemistry , Middle Aged , Oleic Acid/administration & dosage , Oleic Acid/adverse effects , Oleic Acid/chemistry , Skin Cream/adverse effects , Skin Cream/chemistry , Treatment Outcome
13.
Eur J Dermatol ; 30(5): 469-492, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-33021480

ABSTRACT

BACKGROUND: Terminalia chebula (TC) is a deciduous tree of which extracts have demonstrated efficacy for treatment of photodamage, skin aging, and wound healing. However, molecular and cellular mechanisms underlying these benefits remain unclear. OBJECTIVE: To profile dermal expression responses to a standardized tannin-enriched TC fruit extract (Synastol® TC). MATERIALS AND METHODS: Microarrays were used to evaluate gene expression in three-dimensional reconstituted human skin cultures. RESULTS: Genome-wide expression responses to TC were the opposite to those observed in cells exposed to oxidative stress, solar-simulated UV radiation, and wounding, with increased expression of genes associated with water homeostasis, skin barrier establishment, blood vessel development, and circadian rhythms. TC also increased expression of extracellular matrix components, such as collagens (COL1A1, COL1A2) and proteoglycans (PRELP, OGN), and in separate assays, we showed that TC inhibits MMP enzymes (MMP-1, MMP-2, MMP-3, MMP-9, MMP-12) and microbial activity (S. aureus, P. acnes). Unexpectedly, mRNA and protein levels of late keratinocyte (KC) differentiation markers (FLG, LOR) were increased by TC, and expression responses in skin cultures broadly resembled those that occur with KC differentiation. Consistent with these results, TC increased expression of transcription factors regulating KC differentiation (FOS, GHRL3, PPARG) and we noted enrichment of AP-1 binding sites in regions upstream of TC-increased genes. CONCLUSION: These results demonstrate that functionally important TC extract responses occur in the epidermis and are therefore not restricted to the dermal layer. Our findings thus suggest mechanisms by which TC may strengthen full-thickness skin architecture for treatment of skin aging and/or chronic wounds.


Subject(s)
Fruit , Microarray Analysis , Plant Extracts/pharmacology , Skin Aging/drug effects , Skin Aging/genetics , Skin/drug effects , Terminalia , Cell Differentiation , Collagenases/genetics , Extracellular Matrix/genetics , Filaggrin Proteins , Gene Expression , Genome-Wide Association Study , Humans , Keratinocytes/cytology , Oxidative Stress , Skin/injuries , Skin/microbiology , Skin/radiation effects , Tissue Culture Techniques , Ultraviolet Rays/adverse effects
14.
Biochem Biophys Res Commun ; 532(3): 475-481, 2020 11 12.
Article in English | MEDLINE | ID: mdl-32892947

ABSTRACT

Dimethyl fumarate (DMF) has emerged as a first-line treatment for the relapsing-remitting multiple sclerosis (RRMS) subtype. It is hypothesized that DMF has anti-inflammatory and antioxidant effects although mechanisms are not fully understood. This study used RNA-seq to profile gene expression responses to DMF in cultured astrocytes. Responses were compared with those of isosorbide di-(methyl fumarate) (IDMF), a newly designed fumarate that may partially replicate DMF activity with fewer adverse effects. Both compounds altered the expression of MS-associated genes, including those near MS susceptibility loci and genes dysregulated in MS patient astrocytes. The shared DMF/IDMF transcriptome response involved altered expression of antioxidant genes (e.g., HMOX1) and genes linked to extracellular matrix integrity (TIMP3, MMP9) and migration of pro-inflammatory cells into CNS (CCL2). IDMF-specific transcriptome responses included down-regulation of mitotic genes associated with a proliferative reactive astrocyte phenotype (ICAM1) and repression of genes encoding NF-kappaB subunits (NFKB2, RELA, RELB) and NF-kappaB targets (NCAPG, CXCL1, OAS3). Overall, these results identify astrocyte-centered mechanisms that may contribute to the established efficacy of DMF as an RRMS treatment. Furthermore, our findings support a rationale for further studies of IDMF as a novel fumarate, which may have unique suppressive effects on astrocyte reactivity and glial scar formation. [200 words].


Subject(s)
Astrocytes/drug effects , Dimethyl Fumarate/analogs & derivatives , Astrocytes/metabolism , Cells, Cultured , Dimethyl Fumarate/pharmacology , Down-Regulation/drug effects , Drug Evaluation, Preclinical , Genetic Predisposition to Disease , Humans , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase Inhibitors/pharmacology , Mitosis/drug effects , Mitosis/genetics , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/genetics , NF-kappa B/genetics , NF-kappa B/metabolism , Phenotype , Protein Biosynthesis/drug effects , Transcriptome/drug effects
15.
J Invest Dermatol ; 140(3): 602-614.e15, 2020 03.
Article in English | MEDLINE | ID: mdl-31465741

ABSTRACT

Zingerone (Z) is a phenolic alkanone derived from natural sources with anti-inflammatory and antioxidant effects. Acetyl zingerone (AZ) is a recently designed molecule that shares structural features with Z but is expected to have improved stability and antioxidant function. This study utilized microarrays to compare the effects of Z and AZ on gene expression in reconstituted human epidermis. Both Z and AZ increased Notch pathway gene expression (NOTCH1 and MAML3) and decreased expression of genes linked to extracellular matrix disassembly (MMP3 and CTSV) and reactive oxygen species metabolism (PMAIP1 and ARG2). Although Z and AZ each inhibited in vitro matrix metallopeptidase (MMP)-1, MMP-3, and MMP-12 activity, inhibition of MMP-3 and MMP-12 was greater with AZ. Moreover, AZ led to more consistent increases in the expression of genes encoding collagens (COL11A2), proteoglycans (VCAN), and extracellular matrix glycoproteins (SPARC). Finally, AZ opposed gene expression patterns associated with fibroblast senescence, keratinocyte differentiation, and IL-17A stimulation. These effects were AZ-specific and not replicated by Z. These results show that AZ improves extracellular matrix integrity with retinoid-like effects on differentiation and inflammation. Our findings provide a rationale for clinical studies to understand the benefits of AZ in the treatment or prevention of skin aging, or potentially, as a treatment for other human skin diseases.


Subject(s)
Epidermis/drug effects , Extracellular Matrix/drug effects , Gene Expression Regulation/drug effects , Guaiacol/analogs & derivatives , Cell Differentiation , Epidermis/immunology , Epidermis/metabolism , Extracellular Matrix/immunology , Extracellular Matrix/metabolism , Gene Expression Profiling , Gene Expression Regulation/immunology , Guaiacol/chemistry , Guaiacol/pharmacology , Humans , Interleukin-17/metabolism , Matrix Metalloproteinase 12/metabolism , Matrix Metalloproteinase 3/metabolism , Oligonucleotide Array Sequence Analysis , Skin Aging/drug effects , Skin Aging/immunology , Tissue Culture Techniques
16.
Photochem Photobiol ; 82(3): 823-8, 2006.
Article in English | MEDLINE | ID: mdl-16492073

ABSTRACT

Di-2,2'-diethylhexyl-3,5-dimethoxy-4-hydroxy-benzylidenemalonate (INCI name diethylhexyl syringylidene malonate, DESM), the target photostabilizer, was synthesized in one step by condensation of 3,5-dimethoxy-4-hydroxy benzaldehyde (Syringaldehyde) with di-2,2'-diethylhexyl malonate. Photostability data in sunscreen formulations showed that DESM is photostable and improves the photostability of avobenzone significantly when compared to control (without a photostabilizer). Photostable broad-spectrum sunscreen formulations with high SPF (>30) have been achieved by combining avobenzone, DESM and UV-B sunscreens, such as homosalate, octisalate or other UV-B sunscreens. It seems that (a) triplet-state energy transfer from avobenzone to DESM and (b) scavenging of reactive species are responsible for the observed stabilization of avobenzone. In vitro study of the two formulations containing DESM clearly showed critical wavelength of well over 370 nm and can thus be categorized as broad-spectrum sunscreens. DESM does not have any contribution to in vivo SPF; instead it boosts SPF by about 5 units in high-SPF products. DESM was found to be an excellent singlet-oxygen quencher, thereby reducing photodegradation of avobenzone caused by singlet oxygen. In short, the multiplicity of effects and formulation benefits seen with DESM makes it an ideal choice as a unique antioxidant photostabilizer for a variety of cosmetic products targeting young and mature skin alike.


Subject(s)
Radiation-Protective Agents/chemical synthesis , Antioxidants/chemical synthesis , Drug Design , Sunscreening Agents/chemical synthesis , Ultraviolet Rays
18.
Skin Pharmacol Appl Skin Physiol ; 15(5): 374-80, 2002.
Article in English | MEDLINE | ID: mdl-12239434

ABSTRACT

A standardized extract of Phyllanthus emblica (trade named Emblica) was found to have a long-lasting and broad-spectrum antioxidant activity. The product has no pro-oxidation activity induced by iron and/or copper because of its iron and copper chelating ability. Emblica helps protect the skin from the damaging effects of free radicals, non-radicals and transition metal-induced oxidative stress. Emblica is suitable for use in anti-aging, sunscreen and general purpose skin care products.


Subject(s)
Antioxidants/chemistry , Phyllanthus emblica/chemistry , Skin Care/methods , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Fruit/chemistry , Humans , Phytotherapy/methods , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use
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