Article

Healing fats of the skin: The structural and immunologic roles of the Ω-6 and Ω-3 fatty acids

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Abstract

Linoleic acid (18:2omega6) and alpha-linolenic acid (18:3omega3) represent the parent fats of the two main classes of polyunsaturated fatty acids: the omega-6 (n-6) and the omega-3 (n-3) fatty acids, respectively. Linoleic acid and alpha-linolenic acid both give rise to other long-chain fatty acid derivatives, including gamma-linolenic acid and arachidonic acid (omega-6 fatty acids) and docosahexaenoic acid and eicosapentaenoic acid (omega-3 fatty acids). These fatty acids are showing promise as safe adjunctive treatments for many skin disorders, including atopic dermatitis, psoriasis, acne vulgaris, systemic lupus erythematosus, nonmelanoma skin cancer, and melanoma. Their roles are diverse and include maintenance of the stratum corneum permeability barrier, maturation and differentiation of the stratum corneum, formation and secretion of lamellar bodies, inhibition of proinflammatory eicosanoids, elevation of the sunburn threshold, inhibition of proinflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, and interleukin-12), inhibition of lipoxygenase, promotion of wound healing, and promotion of apoptosis in malignant cells, including melanoma. They fulfill these functions independently and through the modulation of peroxisome proliferator-activated receptors and Toll-like receptors.

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... It is not biosynthesized by the body and must be acquired through diet or other external sources. Furthermore, there are reports these fatty acids have regenerating and also healing activity on the skin [10][11][12], both through a proliferative effect on cells and as precursors of inflammatory mediators responsible for tissue repair [13][14][15]. ...
... These levels are considered high, even when compared to traditional oils with high levels of linoleic acid, such sunflower, corn and soybeans, which have average values around 68, 52 and 55% respectively [40,41]. It is known that unsaturated fatty acids, such linoleic acid (omega-6), can affect the healing process by stimulating the proliferation of epithelial cells, presenting therapeutic potential for wound healing, skin regeneration, photo-aging prevention and anti-inflammatory effects [10][11][12]. Furthermore, products for wound healing and bedsores based on sunflower oil, known as EFA (Essential Fatty Acid) oils, are widely used in clinical practice. ...
... Wound healing is divided into inflammatory response, cell proliferation and maturation, where cellular processes in the inflammatory phase of cicatrization are initiated and amplified largely by proinflammatory cytokines. They may have their synthesis and activity regulated by fatty acids, mainly oleic, linoleic and linolenic acids [10,12,77,78]. In addition, these fatty acids have been shown to play a key role in cell membrane structure and skin tissue reconstruction, accelerating the rate of healing, including the proliferative effect on epithelial cells [14,79]. ...
Preprint
Despite the potential of Passiflora spp. as potential as source of bioactive compounds, poor aqueous solubility and stability issues restrict their use in pharmaceutical field. The most suitable approach to overcome such limitations is the development of formulations based on proper delivery systems. Among them, nanoemulsions have been widely used as carrier systems that can guarantee better cutaneous performance of herbal oils. This study evaluated physicochemical properties and cellular effects of seed oils from four varieties of wild Passiflora spp. The fatty acids profile of the seed oils was analyzed by gas chromatography and cell viability assay was performed on J774 macrophages. The nanoemulsions were prepared for the different seeds oils and cell proliferation was evaluated on HaCaT keratinocytes. The oils presented a predominance of unsaturated fatty acids, mainly linoleic acid (>65%) and no cytotoxic effects were observed on J774 cells up to 100 μg/mL. All nanoemulsions presented droplet size about 200 nm, narrow polydispersity index (<0.300) and overall, physicochemical properties consistent with good stability after 90 days of storage. The oils and nanoemulsions induced proliferation of keratinocytes, where nanoemulsions prepared with P. alata oil was the most effective, reaching 150% effect. These findings demonstrate proper cytocompatibility of oils from wild Passiflora spp. and their ability to stimulate the proliferation of keratinocytes, which suggest their potential use as herbal bioactives for dermal healing. Their incorporation in nanoemulsions is an innovative approach for obtaining nanotechnological dermatological products through a sustainable concept that can reach organoleptic characteristics superior to the in natura product.
... It is not biosynthesized by the body and must be acquired through diet or other external sources. Furthermore, there are reports these fatty acids have regenerating and also healing activity on the skin [10][11][12], both through a proliferative effect on cells and as precursors of inflammatory mediators responsible for tissue repair [13][14][15]. ...
... These levels are considered high, even when compared to traditional oils with high levels of linoleic acid, such sunflower, corn and soybeans, which have average values around 68, 52 and 55% respectively [40,41]. It is known that unsaturated fatty acids, such linoleic acid (omega-6), can affect the healing process by stimulating the proliferation of epithelial cells, presenting therapeutic potential for wound healing, skin regeneration, photo-aging prevention and anti-inflammatory effects [10][11][12]. Furthermore, products for wound healing and bedsores based on sunflower oil, known as EFA (Essential Fatty Acid) oils, are widely used in clinical practice. ...
... Wound healing is divided into inflammatory response, cell proliferation and maturation, where cellular processes in the inflammatory phase of cicatrization are initiated and amplified largely by proinflammatory cytokines. They may have their synthesis and activity regulated by fatty acids, mainly oleic, linoleic and linolenic acids [10,12,77,78]. In addition, these fatty acids have been shown to play a key role in cell membrane structure and skin tissue reconstruction, accelerating the rate of healing, including the proliferative effect on epithelial cells [14,79]. ...
Article
Despite the potential of Passiflora spp. as potential as source of bioactive compounds, poor aqueous solubility and stability issues restrict their use in pharmaceutical field. The most suitable approach to overcome such limitations is the development of formulations based on proper delivery systems. Among them, nanoemulsions have been widely used as carrier systems that can guarantee better cutaneous performance of herbal oils. This study evaluated physicochemical properties and cellular effects of seed oils from four varieties of wild Passiflora spp. The fatty acids profile of the seed oils was analyzed by gas chromatography and cell viability assay was performed on J774 macrophages. The nanoemulsions were prepared for the different seeds oils and cell proliferation was evaluated on HaCaT keratinocytes. The oils presented a predominance of unsaturated fatty acids, mainly linoleic acid (>65%) and no cytotoxic effects were observed on J774 cells up to 100 μg/mL. All nanoemulsions presented droplet size about 200 nm, narrow polydispersity index (<0.300) and overall, physicochemical properties consistent with good stability after 90 days of storage. The oils and nanoemulsions induced proliferation of keratinocytes, where nanoemulsions prepared with P. alata oil was the most effective, reaching 150% effect. These findings demonstrate proper cytocompatibility of oils from wild Passiflora spp. and their ability to stimulate the proliferation of keratinocytes, which suggest their potential use as herbal bioactives for dermal healing. Their incorporation in nanoemulsions is an innovative approach for obtaining nanotechnological dermatological products through a sustainable concept that can reach organoleptic characteristics superior to the in natura product.
... The effects of omega 3 fatty acids such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been studied for a plethora of diseases and tissues. At skin level, omega 3 fatty acids are anti-inflammatory (McCusker and Grant-Kels 2010;Yoshida, Yasutomo, and Watanabe 2016). They lower the levels of proinflammatory cytokines such as prostaglandins, leukotrienes, TNF alpha, gamma interferon, IL-12, and IL-6. ...
... They lower the levels of proinflammatory cytokines such as prostaglandins, leukotrienes, TNF alpha, gamma interferon, IL-12, and IL-6. Ultraviolet-induced inflammation, as well as Minimal Erythema Dose (MED), is lessened through supplementation with omega 3 fatty acids (McCusker and Grant-Kels 2010). ...
... The effects of omega 3 fatty acids such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been studied for a plethora of diseases and tissues. At skin level, omega 3 fatty acids are anti-inflammatory (McCusker and Grant-Kels 2010;Yoshida, Yasutomo, and Watanabe 2016). They lower the levels of proinflammatory cytokines such as prostaglandins, leukotrienes, TNF alpha, gamma interferon, IL-12, and IL-6. ...
... They lower the levels of proinflammatory cytokines such as prostaglandins, leukotrienes, TNF alpha, gamma interferon, IL-12, and IL-6. Ultraviolet-induced inflammation, as well as Minimal Erythema Dose (MED), is lessened through supplementation with omega 3 fatty acids (McCusker and Grant-Kels 2010). ...
... When SLS was applied to human skin in vivo, it induced differential expression of cyclooxygenase-2, the enzyme involved in synthesis of PGE 2 [48]. Fatty acids such as SA can also affect gene transcription; and bind to receptors in cell signaling cascades [49][50][51]. In particular, the peroxisome proliferator-activated receptor PPARγ is activated by some fatty acids including linoleic acid present in Delta-5 oil, leading to anti-inflammation in skin [47]. ...
... We did not know a priori what sample size would be appropriate, but the data obtained herein, will be useful for future sample size calculations in more elaborate, future studies. As a first pilot study, our strategy was to maximize potential to observe statistically significant results, albeit with caveats including a limited number of subjects (n = 7) who were not diverse (Caucasian females aged [45][46][47][48][49][50][51][52][53][54][55][56][57][58]. In males, and persons with a tougher skin surface, there would possibly be less damage with SLS, but we would still expect Delta-5 to be effective; this would need to be tested empirically. ...
Article
Full-text available
Background Sciadonic acid (SA) is an anti-inflammatory fatty acid displacing arachidonic acid (ARA) from specific phospholipid pools, thus modulating downstream pro-inflammatory lipid mediators. Its novel anti-inflammatory actions have been studied in vitro, in pre-clinical models, and stemming from testimonials, after topical- and oral application. It has not been tested in a formal clinical study for topical benefits previously. Skin barrier layer was our focus as it has a critically important role in maintaining skin moisture balance. Methods Herein, forearm skin was left undamaged; or barrier layer was chemically-damaged with 2% sodium lauryl sulfate (SLS) for 24 h. SLS-damaged skin was left untreated or treated with Delta-5® oil containing 24% SA twice daily for 27 days. Barrier function was assessed by open chamber transepidermal water loss (TEWL) and skin surface impedance on days 0 (clear skin), -1 (1-day post-SLS), -2 (2-days post-SLS, 1-day post-Delta-5), -3, -7, and − 28. Results Relative to day 1, Delta-5 oil statistically significantly decreased TEWL vs. untreated damaged sites, on days 3 (125% more reduced), -7 (74% more reduced), and − 28 (69% more reduced). Decreases in TEWL following chemical damage indicates improved skin barrier repair and healing. Similar patterns were quantified for skin impedance. There was also reduced redness observed on days 3 and − 7 with Delta-5 oil vs. untreated SLS-damaged skin. Conclusions Delta-5 oil thus has anti-inflammatory potential in human skin, under controlled clinical conditions, to accelerate irritant-induced healing, and improve skin barrier function. Improvement in barrier function would benefit dermatitis, acne, eczema, and skin scarring. In normal skin, Delta-5 oil has potential to promote healthy, moisturized skin; and improve skin structure, elasticity, and firmness.
... These essential fatty acids include alpha-linolenic acid (ALA) and linoleic acid (LA), which are shortchain precursors of omega-3 PUFA such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), and omega-6 PUFA such as arachidonic acid (AA), respectively. These fatty acids cross the blood-brain barrier and influence cellular and inflammatory signaling and contribute to healthy brain development, aging, and neuronal resilience (Janssen and Kiliaan, 2014;McCusker and Grant-Kels, 2010;Rapoport, 2013). Omega-3 and omega-6 PUFA have a complex synergistic and antagonistic relationship (Lin et al., 2015;Luxwolda et al., 2011), and extant evidence indicates that an optimal ratio of omega-6 to omega-3 PUFA is important for mental health and cognitive functioning (Nelson and Raskin, 2019). ...
Article
Alterations in polyunsaturated fatty acids (PUFAs), including omega-3 and omega-6, have been implicated in the pathophysiology of psychotic disorders, but little is known about their associations with neuropsychological functioning. The present study includes 46 recent-onset psychosis patients who participated in a larger (n = 50) double blind, placebo-controlled randomized clinical trial comparing 16 weeks of treatment with either risperidone + fish oil (FO) (EPA 740 mg and DHA 400 mg daily) or risperidone + placebo and completed neuropsychological assessments at the baseline timepoint. We investigated the relationship between baseline omega-3 (i.e., eicosapentaenoic acid, EPA; docosapentaenoic acid, DPA and docosahexaenoic acid, DHA) and omega-6 (i.e., arachidonic acid, AA) PUFA with baseline MATRICS Consensus Cognitive Battery (MCCB) and Brief Psychiatric Rating Scale (BPRS) scores. Twenty-five patients had neuropsychological data available at 16 weeks following participation in the clinical trial, which included 12 patients assigned to risperidone + FO and 13 patients assigned to risperidone + placebo. At baseline both higher DHA and EPA correlated significantly with better social cognition after controlling for functioning on other neuropsychological domains, total BPRS score, AA level and substance use. Also, at baseline higher AA correlated significantly with hostility/uncooperativeness after controlling for DHA + EPA + DPA, overall neuropsychological functioning and substance use. Patients treated with risperidone + FO demonstrated a significant longitudinal increase in social cognition that was significantly higher at 16 weeks compared to patients treated with risperidone + placebo. DHA also correlated significantly with social cognition at the 16-week timepoint. This study provides novel evidence for a differential role of omega-3 vs. omega-6 PUFA in neuropsychological deficits and symptoms in recent-onset psychosis and its treatment.
... Besides, lipoic acid conjugate Lys-Thr-Thr-Lys-Ser (KTTKS) has effective skin whitening and anti-aging agents [21]. Moreover, other studies described positive effects of fatty acids in wound healing [22][23][24][25]. They reported that palmitoyl fatty acid can alter skin structural and immunological status since they constitute the stratum corneum and thus, improve the permeability of the skin. ...
Article
Full-text available
The standard treatment of open wounds via the direct usage of therapeutic agents is not without limitations with respect to healing. Small peptides can create a favorable milieu for accelerating the healing of wounds. This study presents the potential of a novel fatty acid conjugated tetrapeptide (palmitic acid-glycine-aspartic acid-proline-histidine; Palmitoyl-GDPH) in alleviating wound healing. Tetracycline was employed as a standard control drug following its significance in wound healing including biologically active and antimicrobial effects. The peptide in liquid form was applied on to a 4 cm2 full thickness wound surgically induced at the dorsum of Sprague Dawley (SD) rats. The in vivo wound treatment with Palmitoyl-GDPH for eighteen days, histologically demonstrated an almost perfect healing exhibited by increased re-epithelialization, enhanced collagen deposition, and diminished scar formation compared to the controls. In addition, the well-developed epidermal-dermal junction and ultimate stimulation of hair follicle-growth in the Palmitoyl-GDPH treated group indicated the wound to have healed as functionally viable tissues. In general, the much lower hemogram values in the Palmitoyl-GDPH group indicated that the ongoing healing is en route to an earlier recovery. Additionally, the liver, kidney, and pancreas function biomarkers being within normal limits indicated the relatively non-toxic nature of Palmitoyl-GDPH at the used dosage. These results indisputably supported the great potential of this newly synthesized Palmitoyl-GDPH to be used as an effective therapeutic agent for wound healing (this actually means creating a new wound).
... Omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Derivatives of omega-3 fatty acids are thought to influence the skin barrier by acting as transcription factors and decreasing inflammation as immune modulators [35]. ...
Article
Full-text available
Multiple research studies have examined the role of specific dietary interventions and their effects on skin barrier function. The skin barrier is one of the body's first lines of protection against environmental insults, and disruption of this natural line of defense can result in xerosis, irritation, chronic dermatitis, and other cutaneous effects. Multiple laboratory, animal, and human studies have demonstrated that certain dietary interventions have the potential to impact skin barrier function. Measurements of skin barrier function include stratum corneum hydration and transepidermal water loss. In this review, we examine this research and provide an overview of the effects of prebiotics, probiotics, fatty acids, and emerging research on other substances.
... β-carotene, fatty acids, moisturizing agents, fibers, vitamins and carbohydrates are the main chemical composition of pumpkin pulp (23,24). Oral consumption of pumpkin pulp has shown the adjunctive effect on treatments of many skin disorders such as dermatitis (12,25,26).Cutaneous adverse effects of topical corticosteroids occur regularly with prolonged treatment. The most frequent adverse effects include atrophy, striae, rosacea, perioral dermatitis, acne, and purpura (27,28). ...
Article
Background: Hand Eczema (HE) is chronic skin disease with a high prevalence in population. It has negative impact on the quality of life. Due to the public interest in herbal remedies, we attempt to assess the efficacy of pumpkin ointment in treatment of chronic HE in this research. Methods: This study was conducted in an outpatient clinic at Imam-Khomeini Hospital in Tehran (Iran) from May 2015 to Nov 2016. We performed a double-blind trial on 60 patients with chronic HE randomized to four groups included pumpkin, betamethasone, eucerin and almond ointment (n=15 for each group) for 28 days. Patients were ordered to apply ointments twice a day. Hand Eczema Severity Index (HECSI) and Dermatology Life Quality Index (DLQI) of the patients were evaluated by a dermatologist on the 1st, 14th and 28th d after the start of treatment. Results: Patients' DLQI scores in pumpkin and betamethasone group was significant and pumpkin group showed a better response in quality of life (P=0.001). Betamethasone and pumpkin ointment were effective and showed significant improvement compared with almond and eucerin and reduce HECSI scores (P=0.002 and P=0.012 respectively). Betamethasone ointment outcome on HECSI scores in comparison with topical pumpkin was significant (P<0.001). No clinically adverse effects were observed. Conclusion: Although pumpkin ointment showed a better response in patients' DLQI in HE but it was less effective than betamethasone in decreasing HECSI.
... They are used in the treatment of chronic inflammatory diseases such as skin diseases and rheumatism (Barrow & Shahidi, 2008). The medical importance of cyanobacterial PUFAs is attributed to their anti-inflammatory activity (Ishihara et al., 1998), which modulates the expression of proinflammatory mediator genes and signal transduction and suppressing the oxidative stress (C. S. Chang et al., 2010;Weaver et al., 2009 ), also, they have an effective role in epidermis protection as they maintain its structure and immunologic balance (McCusker & Grant-Kels, 2010), that explains their wide application in the treatment of skin diseases. Examples of important PUFAs extracting from microalgae are arachidonic (AA) acids, eicosapentaenoic (EPA), and docosahexaenoic (DHA) ( Table 3). ...
Article
Cyanobacteria are photosynthetic, Gram-negative bacteria that are considered one of the most morphologically diverse groups of prokaryotes with a chief role in the global nutrient cycle as they fixed gaseous carbon dioxide and nitrogen to organic materials. Cyanobacteria have significant adaptability to survive in harsh conditions due to they have different metabolic pathways with unique compounds, effective defensive mechanisms, and wide distribution in different habitats. Besides, they are successfully used to face different challenges in several fields, including industry, aquaculture, agriculture, food, dairy products, pollution control, bioenergy, and pharmaceutics. Analysis of 680 publications revealed that nearly 1630 cyanobacterial molecules belong to different families have a wide range of applications in several fields, including cosmetology, agriculture, pharmacology (immunosuppressant, anticancer, antibacterial, antiprotozoal, antifungal, anti-inflammatory, antimalarial, anticoagulant, anti-tuberculosis, antitumor, and antiviral activities) and food industry. In this review, we nearly mentioned 92 examples of cyanobacterial molecules that are considered the most relevant effects related to anti-inflammatory, antioxidant, antimicrobial, antiviral, and anticancer activities as well as their roles that can be used in various biotechnological fields. These cyanobacterial products might be promising candidates for fighting various diseases and can be used in managing viral and microbial infections. Communicated by Ramaswamy H. Sarma
... 6,7 Further, a deficiency of linoleic acid leads to poor growth, fatty liver, skin lesions, and reproductive failure, while a deficiency of linolenic acid causes reduced vision, abnormal electroretinogram, and perhaps impaired cognition and behavior. 8 Therefore, the separation of fatty acids from crude oil has gained a significant attention in recent years. ...
Article
Adsorption, being techno-economically feasible technique, has gained an attraction to remove low-concentration fatty acid from non-aqueous stream in recent years. In the present work, previous studies on adsorption of unsaturated fatty acid (oleic acid, in particular) have been critically reviewed and an attempt has been made to enhance adsorptive removal of oleic acid. The efficacy of silver ion loaded resin (R-Ag+) for adsorption of oleic acid from non-aqueous streams was demonstrated and compared with other ion-exchange resins. Batch equilibrium adsorption data were fitted to Langmuir adsorption isotherm. Finally, an industrial mixture of fatty acids was subjected to silver ion chromatography for selective removal of fatty acids. Batch equilibrium adsorption data were modeled using Freundlich adsorption isotherm. Adsorption equilibrium constants were determined to estimate the selectivity of linolenic acid over linoleic and oleic acids. Adsorption of oleic acid was favored on R-Ag+ resin from non-polar solvents. The maximum saturation capacity of R-Ag + resin, anion exchange resin, cation exchange resin, and neutral resin was found to be 1.64, 1.41, 1.07, and 1.03 mol/kg, respectively from heptane as a diluent. Linolenic acid was preferentially adsorbed with selectively of 1.40 over oleic acid from industrial fatty acid mixture using silver ion chromatography.
... La deficiencia de DHA ocurre durante el envejecimiento y la demencia, deteriora la memoria y el aprendizaje, y promueve enfermedades neurodegenerativas relacionadas con la edad, incluida la enfermedad de Alzheimer. (8)(9)(10) El envejecimiento cutáneo se puede dividir en envejecimiento cronológico y fotoenvejecimiento. Se activa a través del daño en la piel humana atribuible a la exposición repetida a los rayos UV de la luz solar. ...
Article
Full-text available
Aging in general, and skin aging in particular, is a deleterious and universal process. Skin aging can be divided into chronological aging and photoaging, the latter being activated through damage to human skin, attributable to repeated exposure to ultraviolet (UV) rays from sunlight. Fatty acids derived from fish oil (omega 3) have been considered to be associated with photoprotection of the skin. The objective of this work is to describe the effects of omega 3 as an anti-aging drug in the elderly population. A bibliographic review of articles published between January 2010 and June 2020, in Pubmed and Google Scholar, was carried out. The available literature shows the effect and benefit of these fatty acids in the aging process, which constitute clinical therapies at the dermatological level and in areas of plastic surgery. Its use has a positive effect on the aging process in different organs, through action against oxidative stress.
... 70 Omega-3 fatty acids are hypothesized to competitively inhibit inflammatory pathways, improve skin homeostasis, hydration and thus reduce pruritus. 69,71 Findings from studies by Peck et al. 32 and Begum et al. 33 revealed significant reductions in serum inflammatory biomarker arachidonic acid and leukotriene B4 respectively, but reported non-significant improvement in pruritus severity compared to controls. While promising, there remains insufficient evidence for the recommendation of use of omega-3 fatty acids / fish oil for treatment of UP. ...
Article
Full-text available
Introduction Uremic pruritus (UP) is one of the most bothersome symptoms among chronic kidney disease (CKD) patients. The pathophysiology of UP remains elusive, resulting in limited treatment options. The inability of standard medical treatments to provide effective relief has piqued interest in complementary and alternative medicine (CAM). Methodology A systematic review of randomized controlled trials (RCTs) summarizing the efficacy and safety profile of CAM used for UP in CKD patients was performed. CAM interventions were classified using categories proposed by the National Center for Complementary and Integrative Health. The efficacy of each CAM was determined from changes in UP severity and all reported adverse effects were extracted. Results Of 5242 articles screened, 34 RCTs were included, with 15 (44.1 %) studies having a sample size greater than 50. The studies considered 21 treatments including omega-3 fatty acid supplementation (n=5), acupuncture (n=5), topical capsaicin (n=4) and acupressure (n=3). Acupuncture, acupressure and topical capsaicin were shown to be effective in improving uremic pruritus. Interventions which include oral omega-3 fatty acid and zinc supplementation demonstrated mixed efficacy. Other therapies such as evening primrose oil, turmeric, vitamin B3, vitamin D and thermal therapy were not effective for treatment of UP. Common adverse effects reported with topical capsaicin included mild burning sensations (50.0–88.2 %) or erythema (6.7–22.7%) while that of acupuncture included soreness (7.5 %), bleeding (6.0–7.5%) and hematoma (1.9 %). Conclusions Acupuncture, acupressure and topical capsaicin have the largest body of evidence for efficacy in the treatment of UP. Larger and higher quality RCTs are required to examine the efficacy and safety of promising CAM.
... 43 ALA and its derivative have been found that they may contribute to lamellar body formation, cytokine inhibition, lipoxygenase repression, SC differentiation, and maturation, which might relieve inflammatory-related dermatoses including acne, AD, psoriasis, and lupus. 44,45 SBT seed oil containing abundant OA, LA, and ALA has been validated that had a positive effect on AD through suppression inflammation and repaired lipid metabolism disorders induced by UV exposure. ...
Article
Full-text available
Background Seed oil of sea buckthorn (SBT) is well known to contain high amount of polyunsaturated fatty acid (PUFA), and PUFA is generally acknowledged to promote skin hydration by reducing trans‐epidermal water loss (TEWL). Aims The present study is aimed to investigate that skin hydration offered by SBT seed oil is whether through up‐regulating AQP3 or HAS2 expression. Methods MTT assay was performed to detect cytotoxicity of SBT seed oil, and then, PCR was carried out to explore whether SBT seed oil can increase AQP3 mRNA expression in normal human epidermis keratinocytes (NHEK) cells or not. Immunofluorescence (IF) and Western blot analysis were used to test the protein level expression of AQP3 and HAS2 influenced by SBT seed oil in NHEK cells or in reconstructed epidermis skin model. Results According to the result of MTT assay, all test concentration of SBT seed oil showed no cytotoxicity to cells. 10 μg/mL SBT seed oil treatment evidently increased AQP3 mRNA level compared to negative control (NC). IF and Western blot analysis results demonstrated that AQP3 and HAS2 protein levels in NHEK cells treated with 10 μg/mL SBT seed oil were much higher than that of NC. Finally, treatment with 10 μg/mL SBT seed oil substantially up‐regulated expression of AQP3 and HAS2 protein in reconstructed epidermis skin model in comparison to NC. Conclusions In summary, our study first proved that SBT seed oil can improve skin hydration through increasing AQP3 and HAS2 expressions.
... www.nature.com/scientificreports/ Essential fatty acids have been shown to regulate several cell signaling pathways involved in skin inflammation, dehydration, and tissue degradation 21 . To date, the effects of quinoa derivatives have been investigated only through DNA and mRNA sequencing 12,22 . ...
Article
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The continuous search for natural products that attenuate age-related losses has increasingly gained notice; among them, those applicable for skin care have drawn significant attention. The bioester generated from the Chenopodium quinoa’s oil is a natural-origin ingredient described to produce replenishing skin effects. With this as motivation, we used shotgun proteomics to study the effects of quinoa bioester on human reconstructed epidermis tridimensional cell cultures after 0, 3, 6, 12, 24, and 48 h of exposure. Our experimental setup employed reversed-phase nano-chromatography coupled online with an Orbitrap-XL and PatternLab for proteomics as the data analysis tool. Extracted ion chromatograms were obtained as surrogates for relative peptide quantitation. Our findings spotlight proteins with increased abundance, as compared to the untreated cell culture counterparts at the same timepoints, that were related to preventing premature aging, homeostasis, tissue regeneration, protection against ultraviolet radiation and oxidative damage.
... Linoleic acid is the most abundant fatty acid in the epidermis. Importantly, it is also the precursor to ceramides, a major component of the extracellular lipid matrix that forms the stratum corneum permeability barrier (McCusker and Grant-Kels, 2010). ...
Article
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Sensitive skin is a common condition that concerns many people in the world. This syndrome is defined by the occurrence of unpleasant sensations such as stinging and burning in response to stimuli that normally should not provoke such sensations. The main hypothesis attributed to the occurrence of sensitive skin is the disruption of the epidermal barrier and a greater penetration of substances such as irritants. In keratinocytes, the NF-κB pathway, which plays an important role in orchestrating inflammatory responses, is then activated. Regulation of this activation is a key issue to control inflammation. Due to the wide variety of sensory symptoms, neurosensory dysfunction also represents a mechanism to be considered. Some of the cutaneous nerve endings express TRPA1, a sensor of skin barrier insult, which is involved in a variety of physiological or cellular processes including nociception, itch and neurogenic inflammation. Regulation of such sensor activation is also an issue to consider to control neurosensory dysfunction. Coriander seed oil is a 100% virgin oil of coriander seeds and boasts a unique composition of fatty acids. The soothing effect of coriander seed oil on sensitive skins was investigated by studying its capacity to regulate NF-κB and TRPA1 activation. Coriander seed oil allowed the regulation of NF-κB activation induced by TNF-α in an in vitro model of inflammation in keratinocytes. It also regulated the activation of TRPA1 induced by allyl isothiocyanate in an in vitro model of keratinocytes-neurons co-culture. These results are in favor of a soothing effect of coriander seed oil.
... The preponderance of linoleic and oleic acids determined by GC-MS analysis of seed oil of the MD population reinforced the antifungal activity of P. harmala shown in our study. This is consistent with other studies on the importance of linolenic, linoleic and oleic acids as essential components of seed oil of many plants such as Pongamia pinnata, which exhibited a strong antifungal and antibacterial properties [16,29]. Other studies revealed the effectiveness of Moringa peregrine against several microorganisms [30]. ...
Article
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This investigation included the chemical analysis of Peganum harmala (P. harmala) seed oil and its antifungal properties against 10 fungal species. Seed oils of six populations were analyzed using high performance liquid chromatography (HPLC) and gas chromatograph/mass spectrometry (GC-MS). The HPLC analysis indicated that P. harmala seed oil exhibited a very high level of tocopherol contents, with values in the range of 2385.66-2722.68 mg/100 g. The most abundant tocopherol isomer was δ-tocopherol (90.39%), followed by γ-tocopherol (8.08%) and α-tocopherol (1.14%). We discovered for the first time the presence of tocotrenols in P. harmala seed oils of the six populations studied. The GC-MS analyses revealed that linoleic acid was the main fatty acid (65.17%), followed by oleic acid (23.12%), palmitic acid (5.36%) and stearic acid (3.08%). We also studied the antifungal activity of seed oil of the Medenine (MD) population on ten fungal pathogens. The antifungal effects differed among pathogens and depended on oil concentrations. Seed oil of the MD population caused a significant decrease in mycelial growth of all fungi tested, with values ranging 31.50-82.11%, except for Alternaria sp., which showed no inhibition. The antifungal activity against the 10 selected fungi can be explained by the richness in tocols of the extracted oil and make P. harmala a promising crop for biological control. Furthermore, the importance of fatty acids and the wide geographic spread in Tunisia of this species make this crop a potential source of renewable energy.
... Namely, it has been shown that after application of emulsions on the skin, evaporation of the greatest percentage of water, known as the evaporation phase, is followed by the phase in which lipids from the emulsion penetrate into the epidermis and lead to increased skin hydration (lipidization phase) [37]. In this connection, previous studies reported linoleic acid and α-linolenic acid, which were found in great amount in the investigated wild bilberry seed oil used in the tested creams, to be safe adjunctive treatments for many skin disorders, including atopic dermatitis, psoriasis, acne vulgaris, systemic lupus erythematosus, nonmelanoma skin cancer, and melanoma [38]. In addition, a recent patent described the invention related to the usage of the cis-9, trans-11 isomer of conjugated linoleic acid or a salt or ester thereof to treat or prevent skin inflammation [39]. ...
Article
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Bilberry represents a valuable source of antioxidant substances responsible for its application for the treatment of different conditions (such as inflammation, cardiovascular disease, cancer, diabetes, and different age-related diseases) associated with increased oxidative stress. As oxidative stress might cause skin impairments, we aim to evaluate a topical preparation containing bilberry leaves extract and bilberry seeds oil, obtained as a byproduct of the food industry. To obtain the extracts, the conventional maceration technique for leaves, and supercritical carbon dioxide extraction for seeds were employed. The chemical profile of both actives was achieved by HPLC and GC methods, revealing the presence of phenolic acids (chlorogenic being the most abundant), flavonoids (isoquercetin in the highest amount), and resveratrol in leaves extract, while in seeds oil the essential ω-3 and ω-6 fatty acids were determined in favorable ratio, almost being 1. Antioxidant potential of the wild bilberry extract and seed oil was evaluated using in vitro DPPH and FRAP assays. Finally, effects of the oil-in-water creams with mentioned wild bilberry isolates on the skin were investigated in an in vivo study conducted on healthy human volunteers, revealing the significant beneficial effects when topically applied.
... Fatty acid of sea buckthorn oil may have contributed as structural components. For example, linolenic acid is important for the water permeability barrier of skin as a structural component of ceramides (Larmo et al., 2014;McCusker & Grant-Kels, 2010). ...
Article
Sea buckthorn (Hippophae L.) is a valuable, multipurpose plant extensively grown in Asia, Europe and Canada. In order to use it in the best way for products of human nutrition, it is necessary to recognize its positive aspects and to eliminate the negative ones. The exceptional value of sea buckthorn can be seen in the presence of both lipophilic antioxidants (mainly carotenoids and tocopherols) and hydrophilic antioxidants (flavonoids, tannins, phenolic acids, ascorbic acid) in remarkably high quantities. Some of the main nutrients, especially lipids of advantageous fatty acid composition, contribute to nutritional benefits of sea buckthorn products for a consumer as well. This review article focuses, besides the above mentioned compounds and vitamins, also on other important components, such as sugars, sugar derivatives, fibre, organic acids, proteins, amino acids and mineral elements. The article also deals with the effects of sea buckthorn components on the course of non-enzymatic browning of food and in vivo glycation. In addition, sensory perception of sea buckthorn and its constituents from the consumeŕs point of view is discussed.
... As various alga have a different capacity to synthesize DHA or EPA, the compositions of marine oils vary considerably upon fish species, diet, body part, extraction method employed, and typically lack significant amounts of long chain PUFA when derived from freshwater sources (Mohanty et al., 2016). Their various metabolites are essential in the regulation of inflammation and immune outcomes, similar to their precursors a-linolenic and stearidonic acids (McCusker and Grant-Kels, 2010). While DHA is predominantly found in the brain and retina, EPA shows direct competition with arachidonic acid metabolic pathways, thus reducing pro-inflammatory eicosanoids levels and suppressing inflammation (Lorente-Cebriań et al., 2015). ...
Article
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Botanical oils have a long history of traditional use and are routinely applied to skin care. The focus of this review is to contrast the functionality of skin oils versus the differential biological and toxicological effects of major plant oils, and to correlate them to their compositional changes. In total, over 70 vegetable oils were clustered according to their lipid composition to promote awareness of health practitioners and botanical product manufacturers for the safety and efficacy of oil-based interventions based on their fatty acid profiles. Since multiple skin disorders result in depletion or disturbance of skin lipids, a tailored mixture of multiple botanical oils to simultaneously maintain natural skin-barrier function, promote repair and regeneration of wounded tissues, and achieve corrective modulation of immune disorders may be required. As bioactive constituents of botanical oils enter the human body by oral or topical application and often accumulate in measurable blood concentrations, there is also a critical need for monitoring their hazardous effects to reduce the possible over-added toxicity and promote maximal normal tissue sparing. The review also provides a useful tool to improve efficacy and functionality of fatty acid profiles in cosmetic applications.
... However, for skin care products, quince seed oil is suitable due to the high content of linoleic acid (47.12%). Linoleic acid has better skin barrier repair potential [2,3]. The study shows quince and raspberry fruit processing can benefit from additional processes eliminating waste and offering alternative revenue streams. ...
Conference Paper
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Quince (Chaenomeles japonica (Thunb.) Lindl. Ex Spach) fruit is very hard, with an astringent and sour taste, therefore are commonly used for processing various products: jam, juice, jelly, alcoholic beverages, and others. Waste of quince fruit processing - cake, seeds, and others constitute a high proportion of processed raw material. The amount of waste also depends on the processing technology. The waste can be recycled and obtained for various valuable products. This study presents waste-free processing opportunities for quince and raspberry. By-products of plant origin can be utilized for the production of healthy foods. Quince fruit was cut into slices to produce candied fruit. Waste left after quince processing was collected and seeds were separated from the waste using water. Quince seeds were dried at 45±2 ºC temperature with active ventilation for 15 hours. Dried seeds were stored at room temperature until oil pressing. The pulp of defrosted raspberries was separated using a de-stoning/straining machine. The raspberry puree was lyophilized and milled into a fine powder. By-products left after raspberry processing were mixed with quince slices and sugar and kept for 24 hours. After waste-free processing of quince and raspberries five products were produced: syrup, candied fruit, jam, seedless raspberry powder, and quince seed oil. Yields respectively were 33.1 %, 21.5 %, 28.8 %, 10.2 % and 6.8 %. The total amount of phenolic compounds in the methanol extracts of products (except oil) varied from 212.3 to 1704.8 mg/ 100g. The antiradical activity (in DPPH reaction system) - from 8.8 to 95.9 µmol TE/g. The ratio of omega-6 and omega-3 fatty acids shows quince seed oil is not the most suitable for the food industry. However, the quince seed oil is suitable for skin care products due to its high content of linoleic acid – 47.1 %. The study shows quince and raspberry fruit processing can benefit from additional processes eliminating waste and offering alternative revenue streams. Keywords: quince, raspberry, by-product, waste-free processing, additional revenue
... In this study, mice treated with the COEW cream experienced significantly increased skin hydration and reduced transepidermal water loss (TEWL) compared with control mice, but IgE concentrations were not affected, whereas NC/Nga mice showed a decreased AD score. It has been stated that C. olitorius leaves comprise high fatty acid counts, specially α-linolenic and linoleic acid, and high quantities of antioxidant molecules [31]; these compounds have the ability to reduce inflammation by suppressing activation of ROS and lead to the aggravation of AD [146,147]. According to Ohtani et al. (1995), polysaccharides are known to facilitate skin hydration, and C. olitorius leaves contain a significant amount of mucilaginous polysaccharides, providing adequate skin hydration and reducing skin dryness [20]. ...
Article
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Plant bioactive compounds have gained global significance in terms of both medicinal and economic ramifications due to being easily accessible and are believed to be effective with fewer side effects. Growing relevant clinical and scientific evidence has become an important criterion for accepting traditional health claims of medicinal plants and also supports the traditional uses of Corchorus as folk medicine. C. capsularis and C. olitorius have broad applications ranging from textile to biocomposite, and young leaves and shoots are used as healthy vegetables and have long been used as traditional remedies for fever, ascites, algesia, liver disorders, piles, and tumors in many cultures. This review systematically summarized and emphasized the nutritional attributes, mostly available bioactive compounds, and biological and potential pharmaceutical properties of C. capsularis and C. olitorius, disclosed to users and non-users. Results suggest that various phytochemicals such as cardiac glycosides, phenols, flavonoids, sterols, lipids, and fatty acids were found or analytically identified in different plant parts (leaf, stem, seed, and root), and many of them are responsible for pharmacological properties and their antitumor, anticancer, antioxidant, antinociceptive, anti-inflammatory, analgesic, antipyretic, antiviral, antibacterial, anticonvulsant, antidiabetic and antiobesity, and cardiovascular properties help to prevent and cure many chronic diseases. In addition to their use in traditional food and medicine, their leaves have also been developed for skin care products, and some other possible uses are described. From this review, it is clear that the isolated compounds of both species have great potential to prevent and treat various diseases and be used as functional foods. In conclusion, this comprehensive review establishes a significant reference base for future research into various medical and functional food applications.
... Concerning health benefits, LA plays a crucial role in the structure and function of the main barrier of the skin: the stratum corneum 18 . LA insufficiency leads to an abnormal function of this barrier. ...
Article
Allium ampeloprasum L., commonly known as wild leek, is an edible vegetable that has been cultivated for centuries. However, no detailed studies have been undertaken to valorize A. ampeloprasum seed oil. This study aims to evaluate the physicochemical properties, chemical composition, and antioxidant activity of A. ampeloprasum seed oil. The seed oil content was found to be 18.20%. Gas chromatography-mass spectrometry (GC-MS) showed that linoleic acid (71.65%) was the dominant acid, followed by oleic acid (14.11%) and palmitic acid (7.11%). A. ampeloprasum seed oil exhibited an oxidative stability of 5.22 h. Moreover, γ- and δ-tocotrienols were the major tocols present (79.56 and 52.08 mg/100 g oil, respectively). The total flavonoid content (16.64 µg CE /g oil) and total phenolic content (62.96 µg GAE /g oil) of the seed oil were also determined. The antioxidant capacity of the oil, as evaluated using the ABTS assay (136.30 µM TEAC/g oil), was found to be significant. These findings indicate that A. ampeloprasum seeds can be regarded as a new source of edible oil having health benefits and nutritional properties.
... Linoleic acid is the most abundant fatty acid in the epidermis. Importantly, it is also the precursor to ceramides, a major component of the extracellular lipid matrix that forms the stratum corneum permeability barrier (12). ...
Article
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Sensitive skin is a common condition that affects many people in the world, especially women. This syndrome is defined by the occurrence of unpleasant sensations such as stinging and burning in response to stimuli that should not normally provoke such sensations. Coriander seed oil (CSO) is a 100% virgin oil of coriander seeds and boasts a specific composition of fatty acids, mainly petroselinic acid (60–75%). It has demonstrated its ability to regulate inflammation (NF-κB pathway) and nociception (TRPA1 pathway), two mechanisms supporting sensitive skin, in previous in vitro research. It was, therefore, a good candidate to be tested in vivo on sensitive skin conditions. A pilot clinical study was conducted to evaluate the effect of this ingredient on healthy women showing excessive skin reactions, mainly redness and discomfort when subjected to external stress. The results showed that the daily consumption of 200 mg of CSO for 28 days effectively reduced redness induced by stripping stress and itching induced by stinging stress. It also improved the perception of skin sensitivity and reactivity after 56 days of consumption. These clinical results confirmed that CSO is a promising ingredient to contribute to reducing reactivity in sensitive skin.
... Despite the fact that JQ seed oils contain strong antioxidants it is not recommendable for the food industry regarding a very high omega-6/omega-3 ratio [29,61,72]. However, JQ seed oil is well suited for skincare products regarding the high content of linoleic acid and perfect fitness of linoleic acid/oleic acid ratio [73]. In addition, studies have shown that quince seeds are suitable for other products, such as mucilage preparation, which have various biological activities and possible applications [32,64]. ...
Chapter
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Japanese quince (Chaenomeles japonica) is one of the most underutilized plant species that have high nutrient value and a positive impact on human health. Due to the high content of bio-compounds, such as phenols, vitamin C, triterpenes, fibers, essential amino acids, and microelements, the fruits, leaves, and seeds are excellent raw materials for functional food production. In addition, their biochemical composition and anti-inflammatory, anticancer, and antibacterial properties expanded their uses in the pharmaceutical field. Moreover, it was demonstrated that quince waste after industrial processing is still valuable and suitable for remanufacturing and developing innovative high value-added products, which can provide economic and ecological benefits. This chapter presents the biochemical composition and possible application of C. japonica cultivars Rasa, Darius, and Rondo. The optimization of processing and extraction parameters was evaluated to increase the extraction efficiency of biologically active compounds and to reduce the extraction time and cost of electricity and environmentally harmful solvents. Moreover, the detailed nutritional and pharmacological value of Japanese quince can help for more selective plant organs application. Our study revealed that cultivars Rasa, Darius, and Rondo are very valuable with many new options for utilization, including food, cosmetic, and pharmaceutical industries.
... Free fatty acids (FFAs) play a critical role in maintaining skin homeostasis [6]. Several researchers have studied the composition [7][8][9] and distribution [10] of FFAs in the human skin and have identified a distinct profile, particularly of the epidermis. ...
Article
The vermilion of the human lip is a unique facial area because of certain distinguishing features from the adjacent tissues such as the white lip (skin) and oral mucosa. However, the distinction in terms of molecular distribution between the vermilion and skin has remained unexplored. Therefore, we aimed to map the human lip by mass spectrometry imaging to gain understanding of the free fatty acid distribution in the vermilion. The lip specimens trimmed off during cheiloplasty were analyzed using desorption electrospray ionization–mass spectrometry imaging. Distributions of two monounsaturated fatty acids and three polyunsaturated fatty acids were observed in the human lip tissue: palmitoleic acid (POA) and oleic acid (OA) and linoleic acid (LA), arachidonic acid (AA), and docosahexaenoic acid (DHA), respectively. Although POA, OA, LA, and AA were differentially distributed across the vermilion and skin, DHA showed a higher accumulation in the epithelium of the vermilion compared to that in the skin. Our results clearly demonstrated the difference in fatty acid distributions between the vermilion and skin. The highly abundant DHA in the epithelium of the vermilion may have an antioxidant role and may thus protect the lip from aging. Our findings can provide a novel strategy for treating lip disorders.
... Free fatty acids (FFAs) play a critical role in maintaining skin homeostasis [6]. Several researchers have studied the composition [7][8][9] and distribution [10] of FFAs in the human skin and have identified a distinct profile, particularly of the epidermis. ...
Article
Full-text available
The vermilion of the human lip is a unique facial area because of certain distinguishing features from the adjacent tissues such as the white lip (skin) and oral mucosa. However, the distinction in terms of molecular distribution between the vermilion and skin has remained unexplored. Therefore, we aimed to map the human lip by mass spectrometry imaging to gain understanding of the free fatty acid distribution in the vermilion. The lip specimens trimmed off during cheiloplasty were analyzed using desorption electrospray ionization-mass spectrometry imaging. Distributions of two monounsaturated fatty acids and three polyunsaturated fatty acids were observed in the human lip tissue: palmitoleic acid (POA) and oleic acid (OA) and linoleic acid (LA), arachidonic acid (AA), and docosahexaenoic acid (DHA), respectively. Although POA, OA, LA, and AA were differentially distributed across the vermilion and skin, DHA showed a higher accumulation in the epithelium of the vermilion compared to that in the skin. Our results clearly demonstrated the difference in fatty acid distributions between the vermilion and skin. The highly abundant DHA in the epithelium of the vermilion may have an antioxidant role and may thus protect the lip from aging. Our findings can provide a novel strategy for treating lip disorders.
... Lauric acid (C12:0), myristic acid (C14:0) and palmitic acid (C16:0) increase CHD risk [12,13]. Further, whilst linoleic acid (LA), the most abundant polyunsaturated fatty acid (PUFA) and omega-6 (n-6), is important for healthy skin [14], in excess, dietary n-6 have been linked to an increased risk of obesity and pro-inflammatory effects [15,16]. Finally, an elevated ratio of n-6/n-3 comes with a higher risk of type 2 diabetes, increased CHD and obesity [16][17][18]. ...
Article
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Researching the distinguishing factors of nutritional milk quality is key to sustainable production and addresses increasing media and scientific scrutiny regarding human health effects and ecological impacts of dairy products. Modern Western diets have high omega-6 relative to omega-3 fatty acid (FA) consumption. This ratio in milk can be manipulated by management practices; increasing forage in dairy diets raises omega-3 in milk. Whilst studies identify higher concentrations of nutritionally beneficial FAs in organic dairy, milk from 100% forage-fed cows in the UK has not been investigated. This study explores differences in FA composition between supermarket conventional and organic and Pasture for Life Association (PFLA) milk, collected in April, July and October, 2017. PFLA milk had higher concentrations of conjugated linoleic acid (+94%) and omega-3 (+92%) than conventional milk. Additionally, concentrations of palmitic acid (+11%), omega-6 (+69%) and the ratio of omega-6/omega-3 (+201%) were higher in conventional than PFLA milk. PFLA milk had higher concentrations of alpha-linolenic acid (+39%), conjugated linoleic acid (+30%) and omega-3 (+21%) and lower concentrations of omega-6 (−36%) and a lower ratio of omega-6/omega-3 (−44%) than organic milk. This supports previous studies and demonstrates the scope to improve milk FA profiles further for potential health benefits through pasture-based management.
... 6,7 Further, a deficiency of linoleic acid leads to poor growth, fatty liver, skin lesions, and reproductive failure, while a deficiency of linolenic acid causes reduced vision, abnormal electroretinogram, and perhaps impaired cognition and behavior. 8 Therefore, the separation of fatty acids from crude oil has gained a significant attention in recent years. ...
Article
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Adsorptive removal of acetic acid from aqueous and non-aqueous solutions was carried out using strong base anion exchange resin at 303, 313, and 323 K. The effect of concentration of acetic acid, nature of solvent, and temperature on adsorption of acetic acid and swelling of the resin were investigated. Adsorption of acetic acid and swelling of the resin were favoured in non-polar solvents for a given temperature. Adsorption of acetic acid was favoured at 303 K and decreased with an increase in temperature. Langmuir isotherm model was fitted to equilibrium adsorption data to determine the Langmuir adsorption constant and saturation capacity of the resin. Further, thermodynamic parameters viz. ΔGO, ΔHO, and ΔSO were estimated. The negative values of ΔGO and ΔHO showed that the adsorption of acetic acid on the resin was spontaneous and exothermic in nature.
... Ω-3 fatty acids as phospholipid esters have promise as adjunct treatment for plaque psoriasis (13,14). The fatty acids have multiple roles in the skin, including maturation and differentiation of the stratum corneum, inhibition of proinflammatory eicosanoids and inhibition of proinflammatory cytokines (tumour necrosis factor-alpha, interferon-gamma, and interleukin-12) (15). Improvement of the mean PASI score in the HRO group compared to the control group at 26 weeks was demonstrated in this study. ...
Article
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The effect of omega-3 polyunsaturated fatty acid supplements in patients with Psoriasis vulgaris has previously been investigated, but interventions varied in source, composition, dose, administration route and duration of treatment. The observed beneficial effects in patients with Psoriasis vulgaris using as a dietary supplement prompted this investigation. This randomised, double blind and placebo controlled study was designed and performed to explore the efficacy and safety of herring roe oil supplementation in 64 patients with plaque psoriasis (ClinicalTrials.gov: NCT03359577). The primary end-point was comparing the change in mean Psoriasis Area Severity Index (PASI) scores in the herring roe oil treatment group and the placebo group from baseline to week 26. In the intention-to-treat population, a statistically significant improvement in the mean PASI score was observed with herring roe oil compared to placebo at 26 weeks. In the recruited patient group, the measured improvement was greatest in patients with a PASI score from 5.5-9.9 at baseline.
... In literatures, linoleic acid is also known as omega-6, an essential fatty acid which cannot be synthesized by the human body, only received by dietary consumption. Linoleic acid is an important nutrient for health functions in humans, involving a precursor to ceramides which is a major component of cellular membranes, vitamin D and a variety of hormones [40,41]. Animal studies have shown that a linoleic acid deficiency can cause scaly and itchy skin [23]. ...
Article
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Pumpkin seed oil is a by-product, abundant in nutrients and bioactive components that promote several health benefits. This study aimed to compare chemical compositions, antioxidant, and pharmacological activities of pumpkin seed oils extracted from Cucurbita moschata Duch. Ex Poir. (PSO1) and Cucurbita moschata (Japanese pumpkin) (PSO2) by aqueous enzymatic extraction. An enzyme mixture consisting of pectinase, cellulase, and protease (1:1:1) was used in the enzymatic extraction process. Fatty acid composition of the oils was determined using fatty acid methyl ester/gas chromatographic-mass spectrometry. Antioxidant activity assays were measured by using stable free radical diphenylpicrylhydrazyl, radical cation 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonate, ferric reducing/antioxidant power, and ferric thiocyanate assay. Inhibition of enzymes involving skin aging and whitening process was investigated. Linoleic acid was a major component of all pumpkin seed oils. Additionally, there was also a significant amount of oleic acid, palmitic acid, and stearic acid detected. PSO2 possessed the highest antioxidant activities compared to PSO1 and commercial pumpkin seed oils (COM1 and COM2). Both PSO1 and PSO2 exhibited higher inhibitory effects on hyaluronidase, collagenase, and tyrosinase than the commercials. Therefore, aqueous enzymatic extraction could yield pumpkin seed oils with higher antioxidant, anti-aging, and whitening activities. This is beneficial for further pharmacological studies and can be used as a functional food for skin benefits.
... Some major lipid classes in the skin are free fatty acids (FFAs), ceramides, and cholesterol [10]. FFAs [11] and ceramides [12] show active metabolism in the skin and plays a crucial role in maintaining homeostasis [13]. In addition, cholesterol and its sulfated product, cholesterol sulfate (CS), have essential functions in the skin barrier [14]. ...
Article
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Background The vermilion of the human lip presents characteristic features and undergoes aging faster than the skin. Therefore, knowledge of the vermilion surface-specific functional molecules is important to understand lip aging and formulate lip care products. Previously, we analyzed the free fatty acid distributions and showed that docosahexaenoic acid highly accumulated in the vermilion's epithelium than in the skin. Objective We aimed to explore the functional molecules other than the free fatty acids on the vermilion's surface. Methods Human lip tissues from children and tape-stripped samples from smooth and rough lips of adults were measured by desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Results DESI-MSI of children's lip sections revealed a major distribution of five phospholipid species in the viable layer, but not in the superficial area, of both the vermilion and the skin than that in the underlying tissue. Interestingly, a remarkably higher distribution of cholesterol sulfate was observed in the vermilion's superficial area compared to that in the skin in all subjects under this study. Furthermore, the tape-stripped lip sample showed an overall higher accumulation of cholesterol sulfate in the stratum corneum of the rough lip than that in the smooth lip. Conclusion Our study concluded that cholesterol sulfate has a characteristic distribution to the vermilion's surface and showed an association with the roughness of the lip.
... Due to a lack of the required enzymes, the skin has limited conversion of LA to AA [18]. Fatty acids can be delivered to the epidermis by cellular uptake through lipoprotein receptors, and subsequently they may act to protect the function and appearance of the skin and to modulate the inflammatory response [19,20]. Different PUFAs may relieve symptoms associated with inflammatory skin disorders (e.g., atopic dermatitis (AD)/eczema; psoriasis), most likely through changes in the ratio of pro-and anti-inflammatory eicosanoids [18,21,22]. ...
Article
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Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose–response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy. <br/
... This observation revealed that both fish oil and the anti-LT medicines were objectively influential in mitigating inflammation and hyperpnoea-persuaded bronchoconstriction [43]. Conversely, dietary supplementation of PUFA for continuously 6 weeks (approximately 120 mg/day) led to an improvement in infant bronchial asthma's lung functioning [44]. Particularly, ω-3 and ω-6 PUFAs are useful against exercise-stimulated bronchoconstriction that acts as key limiting factor in the performance of athletes. ...
Article
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Purpose of Review Polyunsaturated fatty acids (PUFAs) are obtained from various sources, which can be incorporated in the routine diet to maintain the health. They provide protection from several diseases like osteoarthritis, cancer, and autoimmune disorders. Major focus is given to the PUFAs omega-3 (ω-3) and omega-6 (ω-6) fatty acids which are available in both terrestrial and in the marine environment. The main concern of this article is to review the key scientific reports in context with the human health consequences and advantages of the food sources of ω-3 and ω-6 fatty acids. Recent Findings ω-3 and ω-6 fatty acids are consumed by the population globally in the form of foods that are rich in fatty acids. Their nutritional effects have the capability to improve the physical functioning and metabolic rate of the body. Summary These PUFAs contribute in various cellular activities like cell signaling, structural integrity and fluidity of cell membrane, the regulation of blood pressure, glucose level, the nervous system, inflammatory reactions, and hematic clotting. Animal and cell-based models represent that ω-3 and ω-6 PUFAs can regulate the skeletal muscle metabolism. The main concern of this article is to review the key scientific reports in context with the human health consequences and advantages of the food sources of ω-3 and ω-6 fatty acids.
Article
Background The serum levels of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (AA) under the state of pressure ulcers (PUs) are still unclear. Introduction: In order to investigate serum levels of DHA, EPA, and AA in PUs rats, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) method was developed and validated. Methods Chromatographic separation of DHA, EPA, AA was carried out on a BEH C18 column and gradient elute consisted of 5 mM ammonium acetate-0.1% formic acid and acetonitrile. Subsequently, fifty rats were divided into five groups (n=10), four PU groups (A-D) underwent various pressure and release time protocols, with group E as the control. The concentrations of DHA, EPA, AA from five groups were determination using validated method. Results The results showed there was good linearity for DHA (327.3/283.4), EPA (301.2/257.0), and AA (303.1/258.9) within 0.05-6.4 μg/mL. In control group, the levels of DHA, AA and EPA were 1.16±0.68, 0.59±0.19 and 0.78±0.21 μg/mL. At the end of modeling, concentrations of DHA, EPA and AA were increased after long and persistent pressure (>8 h). Especially, the level of DHA was significantly higher (P<0.01) than that of control group. Conclusion A stable, reliable and accurate UPLC-MS/MS for determination of DHA, EPA, AA in blood was developed. Serum concentrations of DHA, EPA and AA were altered differently after long and persistent pressure (>8 h), and DHA is a remarkable one.
Article
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The skin exposome is defined as the totality of environmental exposures over the life course that can induce or modify various skin conditions. Here, we review the impact on the skin of solar exposure, air pollution, hormones, nutrition and psychological factors. Photoageing, photocarcinogenesis and pigmentary changes are well‐established consequences of chronic exposure of the skin to solar radiation. Exposure to traffic‐related air pollution contributes to skin ageing. Particulate matter and nitrogen dioxide cause skin pigmentation/lentigines, while ozone causes wrinkles and has an impact on atopic eczema. Human skin is a major target of hormones, and they exhibit a wide range of biological activities on the skin. Hormones decline with advancing age influencing skin ageing. Nutrition has an impact on numerous biochemical processes, including oxidation, inflammation and glycation, which may result in clinical effects, including modification of the course of skin ageing and photoageing. Stress and lack of sleep are known to contribute to a pro‐inflammatory state, which, in turn, affects the integrity of extracellular matrix proteins, in particular collagen. Hormone dysregulation, malnutrition and stress may contribute to inflammatory skin disorders, such as atopic dermatitis, psoriasis, acne and rosacea.
Chapter
The skin is the interfacing barrier to the external environment. Its integrity is required for protection and health. The cells are continuously being replaced in response to both intrinsic and extrinsic forces. Diet and lifestyle affect the skin health. Genetic makeup, including microRNA, also impacts the degree of skin disease. The incorporation of adequate protein, essential fatty acids, low-glycemic carbohydrates, fermented foods, water, minerals, vitamins, and phytonutrient-rich vegetables modulate the endocrine and immunologic systems of the skin, providing the best opportunity for health. Nutritional requirements for this organ system vary widely depending on its state of health or condition. Common skin ailments are impacted by medical nutrition therapies that can alter the severity of the condition. The application of food and dietary choices, the modified elimination diet, and nutrient or bioactive supplementation may impact the root causes of the skin condition. Dermatologic conditions are common in clinical practice. Common conditions may be a result of underlying metabolic dysfunction (acanthosis nigricans); immunologic epigenetic perturbations (psoriasis and pemphigus); the gut-brain-skin axis dysfunction (acne vulgaris and acne rosacea); genetic or acquired deficiency (zinc and acrodermatitis enteropathica, follicular hyperkeratosis); food-triggered hypersensitivity (dermatitis herpetiformis); a multifactorial imbalance of genetic, environmental, innate, and acquired immune dysfunction (atopic dermatitis); and frank deficiency (pellagra, scurvy). These conditions may respond to targeted medical nutrition therapy. The therapeutic opportunities for each common condition are reviewed.
Article
Background: Fatty acids increase ATP-binding cassette ABC transporter A12 (ABCA12) levels via an increase in peroxisome proliferator-activated receptor β/δ (PPAR β/δ). Promoting lipid transport to lamellar granules has been suggested to improve epidermal barrier function in patients with dry skin. Objective: We investigated whether mevalonolactone (MVL) produced by Saccharomycopsis fibuligera improves dry skin by promoting ABCA12 expression and the amount of free fatty acids in epidermal keratinocytes. Methods: We examined whether MVL increases ABCA12 mRNA and protein levels and the amount of Nile red-positive lipids in cultured epidermal keratinocytes and in a three-dimensional epidermal model by cell staining. Promotion of fatty acid production by MVL was analyzed by liquid chromatography-mass spectrometry. We also evaluated whether MVL addition increases PPAR β/δ mRNA expression in cultured keratinocytes. Based on the results, a randomized controlled trial was conducted in which milky lotions containing MVL and placebo were applied to dry facial skin of healthy female volunteers in winter. Results: MVL increased ABCA12 mRNA and protein levels and lamellar granule number and size. Fatty acid analysis revealed that MVL elevated myristic acid, palmitic acid, and palmitoleic acid levels as well as PPAR β/δ mRNA expression. In human tests, milky lotions containing MVL were shown to significantly improve transepidermal water loss (TEWL) in the stratum corneum compared to placebo. Conclusion: The results suggest that MVL increases fatty acid uptake and ABCA12, promotes fatty acid transport to lamellar granules, and improves epidermal barrier function in dry skin through increased expression of PPAR β/δ.
Article
PurposeThe pharmaceutical industry has been searching for drugs that aim at the prevention, the protection, and the recovery of the skin. Thus, the aim of this study was to evaluate the anti-inflammatory and anti-edematogenic activities of a topical emulsion containing Helianthus annuus oil (5%), glycerin (30%), and vitamin B3 (5%).Methods The aim was verified through chronic inflammatory responses and edema that were induced by irritant croton oil in the ears of mice, followed by histological and leukocyte infiltration. The study also affirmed the stability and the cytotoxicity of the emulsion.ResultsA stable, homogeneous, shiny, slightly-white, and gelatinous emulsion was obtained. The cytotoxicity evaluation allowed for the verification that only in high concentrations were unsatisfactory results presented. The treatment was effective in reversing the inflammatory parameters that were induced by croton oil, such as edema, neutrophil migration, and cell hyperproliferation.Conclusion The developed emulsion containing sunflower oil, glycerin, and vitamin B3 had parameters of stability and presented anti-inflammatory activities. The researchers’ findings suggest that the topical use of this formulation is a new and novel strategy for the treatment of inflammatory conditions of the skin.
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At the beginning of the twenty- first century, the science of human nutrition has been considered as a way for improving life quality and wellness. The role of food in human health and the awareness of consumers for healthy food directed research towards the production of food that has specific health effects on disease prevention and treatment. These foods are satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond adequate nutrition. These foods are termed functional foods. Production of omega-3 table eggs as functional food is a new paradigm in poultry for. The ability of monogastric animals to deposited dietary fatty acids in their tissues without significant modifications on the sensory value of these products was the foundation stone and the starting point to produce omega-3 eggs. Several research activities have been conducted to increase the level of omega-3 polyunsaturated fatty acids in poultry products. The working knowledge of current literature concerning this topic made the strong foundation to produce this type of functional foods. The dietary sources of omega-3 fatty acids used for feeding laying hens modified the fatty acid content of the egg yolk. Some sources deposited amounts of fatty acids made those eggs suitable to be served as functional food. Increasing omega-3 polyunsaturated fatty acid content of eggs could be achieved either by enrichment of the diet with alpha-linolenic rich sources such as flaxseed, linseed or by EPA and DHA rich fish oil and fish meal.
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Insulin Resistance Associated Acne alludes to a subset of acne vulgaris that is driven by exaggerated insulin/IGF-1 signalling. It has a distinctive clinical profile defined by attendant companion morphologies, notably, acanthosis nigricans and benign cutaneous hyperplasias. It has comorbidities derived from hormonal disturbances (PCOS), immune dysfunction, hypovitaminoses, and features of evolving metabolic syndrome. It begins earlier than acne vulgaris, commonly as preadolescent acne, and can be predicted to persist as adult acne, even beyond menopause. It is a spectral entity with complex pathogenesis with mTORC1 overactivity as the most important aberration. It demands additional therapeutic interventions such as insulin-sensitizing agents and mTORC1 inhibitors.
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Purpose: Unlike eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the relationship between eicosatetraenoic acid (ETA) and psoriasis remains unclear. Therefore, We performed a cross-sectional study in the general American population to investigate the association between daily dietary ETA, EPA, and DHA intake and the risk of psoriasis. Participants and methods: This study applied data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2009-2014. Dietary n3 polyunsaturated fatty acids (PUFA) were calculated based on two 24-hour dietary recall interviews. We defined psoriasis by responding to the question "Have you ever been told by a doctor or other health care professional that you had psoriasis?". Multivariable logistic regression analysis, trend tests, subgroup analysis, and interaction tests were used to evaluate the associations of ETA, EPA, and DHA intake with the risk of psoriasis, respectively. Results: A total of 15,733 participants were included in this study. In our optimal multivariate-adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of psoriasis were 0.30 (0.12, 0.88), 1.92 (0.78, 4.74), 1.28 (0.72, 2.27) for daily dietary ETA, EPA, and DHA intake, respectively. Trend tests showed a dose-effect relationship between daily dietary ETA intake and the lower risk of psoriasis. Subgroup analysis and tests for interaction showed that the association was stable in different subgroups. Conclusion: Our study revealed that there might be a dose-effect association of daily dietary ETA intake with the lower risk of psoriasis in American adults.
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Nutraceuticals are considered as a safe alternative to allopathic medicine and therefore are widely used for wound healing as well as part of antiaging cosmetics. In this chapter, we describe the anatomy and physiology of skin followed by the current understanding of the wound healing process. Finally, we describe some well-known nutraceuticals that have shown wound healing potential and antiaging properties on the skin. As skin nutraceuticals are an upcoming market, knowledge about phytoconstituents, their mechanisms of action, and therapeutic uses are essential.
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Recent studies suggest: that the epidermis and pilosebaceous epithelium are important sites of de novo sterol synthesis, and that the rate of cutaneous cholesterol synthesis does not change with alterations in circulating sterol levels. Since cutaneous sterols may be important for permeability barrier function, we studied the effect of experimentally altered barrier function on de novo sterologenesis in the epidermal and dermal layers of the skin. Epidermal sterologenesis appeared to be modulated by the skin's barrier requirements because topical detergent and acetone treatment stimulated de novo synthesis of nonsaponifiable lipids in the epidermis, but not in the dermis. Synthetic activity paralleled both the return of barrier function toward normal and the extent of prior damage to the barrier. Moreover, plastic-wrap occlusion of solvent-treated sites simultaneously corrected both the barrier abnormality and normalized sterol synthesis, further linking increased epidermal sterologenesis to barrier requirements. Whereas topical applications of a variety of other topical lipids did not down-regulate synthesis, epicutaneously applied 25-hydroxycholesterol appeared to diminish synthesis. These results suggest that maintenance of barrier function is one purpose of epidermal de novo nonsaponifiable lipid synthesis, and demonstrate further that, despite a lack of low density lipoprotein receptors, epidermis can regulate its lipid-synthetic apparatus in response to certain specific requirements.
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The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors that is predominantly expressed in adipose tissue, adrenal gland and spleen. PPAR-gamma has been demonstrated to regulate adipocyte differentiation and glucose homeostasis in response to several structurally distinct compounds, including thiazolidinediones and fibrates. Naturally occurring compounds such as fatty acids and the prostaglandin D2 metabolite 15-deoxy-delta prostaglandin J2 (15d-PGJ2) bind to PPAR-gamma and stimulate transcription of target genes. Prostaglandin D2 metabolites have not yet been identified in adipose tissue, but are major products of arachidonic-acid metabolism in macrophages, raising the possibility that they might serve as endogenous PPAR-gamma ligands in this cell type. Here we show that PPAR-gamma is markedly upregulated in activated macrophages and inhibits the expression of the inducible nitric oxide synthase, gelatinase B and scavenger receptor A genes in response to 15d-PGJ2 and synthetic PPAR-gamma ligands. PPAR-gamma inhibits gene expression in part by antagonizing the activities of the transcription factors AP-1, STAT and NF-kappaB. These observations suggest that PPAR-gamma and locally produced prostaglandin D2 metabolites are involved in the regulation of inflammatory responses, and raise the possibility that synthetic PPAR-gamma ligands may be of therapeutic value in human diseases such as atherosclerosis and rheumatoid arthritis in which activated macrophages exert pathogenic effects.
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Ligands and activators of the nuclear hormone receptor superfamily are important in the regulation of epidermal development and differentiation. Previously, we showed that naturally occurring fatty acids, as well as synthetic ligands for the peroxisome proliferator-activated receptor, induce keratinocyte differentiation in vitro. Here we asked whether oxysterols, another class of lipids formed de novo in the epidermis and that activate liver X-activated receptor, regulate keratinocyte differentiation, mRNA and protein levels of involucrin and transglutaminase 1, markers of differentiation, increased 2- to 3-fold in normal human keratinocytes incubated in the presence of 25- or 22R-hydroxycholesterol in low calcium. In high calcium, which alone induces differentiation, mRNA levels were further increased by oxysterols. Rates of cornified envelope formation, an indicator of terminal differentiation, also increased 2-fold with oxysterol treatment. In contrast, the rate of DNA synthesis was inhibited approximately 50% by oxysterols. Transcriptional regulation was assessed in keratinocytes transfected with either transglutaminase 1 or involucrin promoter-luciferase constructs. 22R-hydroxycholesterol increased transglutaminase 1 and involucrin promoter activity 2- to 3-fold. Either deletion of the -2452 bp to -1880 bp region of the involucrin promoter, or mutation of the AP-1 site within this region, abolished oxysterol responsiveness. Moreover, increased AP-1 DNA binding was observed in oxysterol-treated keratinocytes by gel shift analyses. Finally, we demonstrated the presence of liver X-activated receptor α and β mRNAs, and showed that oxysterols stimulate a liver X-activated receptor response element transfected into keratinocytes. These data suggest that oxysterols induce keratinocyte differentiation, in part through increased AP-1-dependent transcription of the involucrin gene, an effect that may be mediated by liver X-activated receptor.
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Peroxisome proliferator-activated receptors, PPARalpha, PPARbeta/delta and PPARgamma, are fatty acid activated transcription factors that belong to the nuclear hormone receptor family. While they are best known as transcriptional regulators of lipid and glucose metabolism, evidence has also accumulated for their importance in skin homeostasis. The three PPAR isotypes are expressed in rodent and human skin. Various cell culture and in vivo approaches suggest that PPARalpha contributes to fetal skin development, to epidermal barrier maturation and to sebocyte activity. PPARbeta/delta regulates sebocyte differentiation, promotes hair follicle growth and has pro-differentiating effects in keratinocytes in normal and inflammatory conditions. In contrast, the role of PPARgamma appears to be rather minor in keratinocytes, whereas its activity is required for sebaceous gland differentiation. Importantly, PPARalpha and beta/delta are instrumental in skin repair after an injury, each of them playing specific roles. Due to their collective diverse functions in skin biology, PPARs represent a major research target for the understanding and treatment of many skin diseases, such as benign epidermal tumors, papillomas, acne vulgaris and psoriasis.
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Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by a defective skin barrier function. Recent studies have reported mutations of the skin barrier gene encoding filaggrin in a subset of patients with AD. We investigated whether reduced filaggrin expression was found in patients with AD who were not carriers of known filaggrin mutations and whether filaggrin expression was modulated by the atopic inflammatory response. Filaggrin expression was measured in skin biopsies and cultured keratinocytes using real-time RT-PCR and immunohistochemistry. Filaggrin loss-of-function mutations were screened in a total of 69 subjects. Compared with normal skin, filaggrin expression was significantly reduced (P < .05) in acute AD skin, with further reduction seen in acute lesions from 3 European American subjects with AD who were heterozygous for the 2282del4 mutation. This was confirmed by using immunohistochemistry. AD skin is characterized by the overexpression of IL-4 and IL-13. Keratinocytes differentiated in the presence of IL-4 and IL-13 exhibited significantly reduced filaggrin gene expression (0.04 +/- 0.01 ng filaggrin/ng glyceraldehyde 3-phosphate dehydrogenase; P < .05) compared with media alone (0.16 +/- 0.03). Patients with AD have an acquired defect in filaggrin expression that can be modulated by the atopic inflammatory response. The atopic immune response contributes to the skin barrier defect in AD; therefore, neutralization of IL-4 and IL-13 could improve skin barrier integrity.
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Several studies have suggested that the n-3 fatty acids Docosahexaenoic (DHA) and Eicosapentaenoic (EPA) have an important protective effect on colorectal cancer, and this could be at least partly due to their proapoptotic activity. It is unclear, however, how this phenomenon is triggered and what mechanisms are implicated. Here, we show that both DHA and EPA have an important proapoptotic effect on colorectal cancer cells with different molecular phenotypes but not in noncancerous cells. Apoptosis is caspase dependent, and both intrinsic and extrinsic pathways are implicated. The dimerization of Bax and Bak, the depolarization of the mitochondrial membrane, and the subsequent release of cytochrome c and Smac/Diablo to the cytosol evidence the activation of the intrinsic pathway. The implication of the extrinsic pathway is shown by the activation of caspase-8, along with the down-regulation of FLIP. The timing of caspase-8 activation, and the oligomerization of Bid with Bax, suggest a cross-talk with the intrinsic pathway. None of the death receptors that commonly initiate the extrinsic pathway: FAS, TNF-R1, and TRAIL-R2 are found to be responsible for triggering the apoptosis cascade induced by DHA and EPA. Neither PPARgamma nor cyclooxygenase-2, two likely candidates to regulate this process, play a significant role. Our findings suggest that the down-regulation of two key regulatory elements of the extrinsic and intrinsic pathways, FLIP and XIAP, respectively, is determinant in the induction of apoptosis by DHA and EPA. These fatty acids could potentially be useful adjuvant anticancer agents in combination with other chemotherapeutic elements.
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The strong bactericidal properties of lauric acid (C12:0), a middle chain-free fatty acid commonly found in natural products, have been shown in a number of studies. However, it has not been demonstrated whether lauric acid can be used for acne treatment as a natural antibiotic against Propionibacterium acnes (P. acnes), which promotes follicular inflammation (inflammatory acne). This study evaluated the antimicrobial property of lauric acid against P. acnes both in vitro and in vivo. Incubation of the skin bacteria P. acnes, Staphylococcus aureus (S. aureus), and Staphylococcus epidermidis (S. epidermidis) with lauric acid yielded minimal inhibitory concentration (MIC) values against the bacterial growth over 15 times lower than those of benzoyl peroxide (BPO). The lower MIC values of lauric acid indicate stronger antimicrobial properties than that of BPO. The detected values of half maximal effective concentration (EC(50)) of lauric acid on P. acnes, S. aureus, and S. epidermidis growth indicate that P. acnes is the most sensitive to lauric acid among these bacteria. In addition, lauric acid did not induce cytotoxicity to human sebocytes. Notably, both intradermal injection and epicutaneous application of lauric acid effectively decreased the number of P. acnes colonized with mouse ears, thereby relieving P. acnes-induced ear swelling and granulomatous inflammation. The obtained data highlight the potential of using lauric acid as an alternative treatment for antibiotic therapy of acne vulgaris.
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Three novel members of the Xenopus nuclear hormone receptor superfamily have been cloned. They are related to each other and similar to the group of receptors that includes those for thyroid hormones, retinoids, and vitamin D3. Their transcriptional activity is regulated by agents causing peroxisome proliferation and carcinogenesis in rodent liver. All three Xenopus receptors activate the promoter of the acyl coenzyme A oxidase gene, which encodes the key enzyme of peroxisomal fatty acid beta-oxidation, via a cognate response element that has been identified. Therefore, peroxisome proliferators may exert their hypolipidemic effects through these receptors, which stimulate the peroxisomal degradation of fatty acids. Finally, the multiplicity of these receptors suggests the existence of hitherto unknown cellular signaling pathways for xenobiotics and putative endogenous ligands.
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Disruption of the permeability barrier results in an increase in cholesterol synthesis in the epidermis. Inhibition of cholesterol synthesis impairs the repair and maintenance of barrier function. The increase in epidermal cholesterol synthesis after barrier disruption is due to an increase in the activity of epidermal HMG-CoA (3-hydroxy-3-methylglutaryl CoA) reductase. To determine the mechanism for this increase in enzyme activity, in the present study we have shown by Western blot analysis that there is a 1.5-fold increase in the mass of HMG-CoA reductase after acute disruption of the barrier with acetone. In a chronic model of barrier disruption, essential fatty acid deficiency, there is a 3-fold increase in the mass of HMG-CoA reductase. Northern blot analysis demonstrated that after acute barrier disruption with acetone or tape-stripping, epidermal HMG-CoA reductase mRNA levels are increased. In essential fatty acid deficiency, epidermal HMG-CoA reductase mRNA levels are increased 3-fold. Thus, both acute and chronic barrier disruption result in increases in epidermal HMG-CoA reductase mRNA levels which could account for the increase in HMG-CoA reductase mass and activity. Additionally, both acute and chronic barrier disruption increase the number of low density lipoprotein (LDL) receptors and LDL receptor mRNA levels in the epidermis. Moreover, epidermal apolipoprotein E mRNA levels are increased by both acute and chronic perturbations in the barrier. Increases in these proteins in response to barrier disruption may allow for increased lipid synthesis and transport between cells and facilitate barrier repair.
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Although the lipids of mammalian stratum corneum are known to be important for the cutaneous permeability barrier, the factors that regulate epidermal lipid biosynthesis are poorly understood. Recent studies suggest that cutaneous sterol synthesis is regulated by cutaneous barrier requirements, while the levels of circulating sterols do not play a role. Whether cutaneous barrier requirements regulate epidermal lipogenesis in general and the nature of the signal that activates the lipid biosynthetic apparatus are unknown. We determined whether alterations of the cutaneous permeability barrier, induced by treatment with a solvent (acetone), a surfactant, sodium dodecyl sulfate (SDS), or essential fatty acid deficiency (EFAD), provoked a discrete versus global stimulation of epidermal and dermal lipid biosynthesis. Acetone treatment increased epidermal, but not dermal, sterol and fatty acid biosynthesis approximately threefold over controls at 1-4 hr, which returned to normal after 12 hr. SDS treatment likewise stimulated epidermal sterol and fatty acid biosynthesis, but the increase was less dramatic than in acetone-treated animals. Since plastic occlusion blocked the expected increase in de novo lipid biosynthesis in acetone-treated animals, it is possible that water flux provides the molecular signal for de novo synthesis. Finally, EFAD mice also demonstrated enhanced epidermal sterol and fatty acid biosynthesis in comparison to normals, an effect that also was abolished when transepidermal water loss was normalized by occlusion, despite the presence of ongoing EFAD. These results demonstrate that disruption of the cutaneous permeability barrier stimulates a parallel, global boost in both sterol and fatty acid biosynthesis that is limited to the epidermis. Since such stimulation is reversed by restoration of barrier function, transcutaneous water gradients may regulate epidermal lipogenesis.
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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily. They are divided into three subtypes (α, β or δ, and γ) and are involved in lipid and glucose homeostasis and in the control of inflammation. In this study, we analyzed the expression of PPARs in murine dendritic cells (DCs), the most potent antigen presenting cells. We find that immature as well as mature spleen-derived DCs express PPARγ, but not PPARα, mRNA and protein. We also show that the PPARγ activator rosiglitazone does not interfere with the maturation of DCs in vitro nor modifies their ability to activate naive T lymphocytes in vivo. Finally, we present evidence that PPARγ activators down-modulate the CD40-induced secretion of interleukin-12, a potent Th1-driving factor. These data suggest a possible role for PPARγ in the regulation of immune responses.
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Background: Ligands of nuclear hormone receptors such as glucocorticoid, retinoid and vitamin D are useful antipsoriatic drugs. Peroxisome proliferator-activated receptors (PPARs), which also belong to the nuclear hormone receptor superfamily, are pleiotropic regulators of growth and differentiation in many cell types, including the keratinocytes. Recent reports have dealt with the involvement of PPARα in epidermal processes such as barrier development, proliferation and differentiation. In a pilot study of topical clofibrate, a PPARα ligand, we did not find any antipsoriatic activity. No study on the effect of topical application of other PPAR subtype ligands (PPARβ/δ and γ) has been published. Objectives: The purpose of this pilot study is to explore the clinical efficacy of the topical application of potent PPARβ/δ and γ agonists on plaque psoriasis, tetradecylthioacetic acid (TTA) and rosiglitazone, respectively. Methods: In a pilot study on psoriatic patients, 8 individuals (5 male/3 female) were treated twice daily for 30 days with vehicle (n = 14 plaques), rosiglitazone 0.5&percnt; (n = 18) and TTA 0.5&percnt; (n = 18). Assessments of the PASI plaque score were carried out on days 0, 4, 7, 11, 14 and 30. Results: No statistically significant difference was found at any of the examination times, between vehicle, rosiglitazone and TTA in terms of reduction of the PASI plaque score for total, scale and infiltration scores. Treatments were well tolerated, and skin irritation, adverse drug-related symptoms and dropouts did not occur. Conclusions: With the reservations due to the limited nature of this pilot trial, it seems that these topical PPARβ/δ and γ agonists do not exert a strong antipsoriatic effect when used alone at 0.5&percnt;.
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In previous studies we have shown that experimental permeability barrier disruption leads to an increase in epidermal lipid and DNA synthesis. Here we investigate whether barrier disruption also influences keratins and cornified envelope proteins as major structural keratinocyte proteins. Cutaneous barrier disruption was achieved in hairless mouse skin by treatments with acetone occlusion, sodium dodecyl sulfate, or tape-stripping. As a chronic model for barrier disruption, we used essential fatty acid deficient mice. Epidermal keratins were determined by one- and two-dimensional gel electrophoresis, immunoblots, and anti-keratin antibodies in biopsy samples. In addition, the expression of the cornified envelope proteins loricrin and involucrin after barrier disruption was determined by specific antibodies in human skin. Acute as well as chronic barrier disruption resulted in the induction of the expression of keratins K6, K16, and K17. Occlusion after acute disruption led to a slight reduction of keratin K6 and K16 expression. Expression of basal keratins K5 and K14 was reduced after both methods of barrier disruption. Suprabasal keratin K10 expression was increased after acute barrier disruption and K1 as well as K10 expression was increased after chronic barrier disruption. Loricrin expression in mouse and in human skin was unchanged after barrier disruption. In contrast, involucrin expression, which was restricted to the granular and upper spinous layers in normal human skin, showed an extension to the lower spinous layers 24 h after acetone treatment. In summary, our results document that acute or chronic barrier disruption leads to expression of keratins K6, K16, and K17 and to a premature expression of involucrin. We suggest that the coordinated regulation of lipid, DNA, keratin, and involucrin synthesis is critical for epidermal permeability barrier function.Keywords: loricrin
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Peroxisome proliferator-activated receptors (PPARs) are pleiotropic regulators of growth and differentiation of many cell types. We have performed a comprehensive analysis of the expression of PPARs, transcriptional cofactors, and marker genes during differentiation of normal human keratinocytes using a combination of reverse transcriptase polymerase chain reaction, Northern and Western blotting, and immunohistochemistry. PPAR was the predominant PPAR subtype in human keratinocytes and highly expressed in basal cells and suprabasal cells. Induction of PPAR and PPAR expression was linked to differentiation, and accordingly, expression of PPAR and PPAR was in essence confined to suprabasal cells. Differentiation was not accompanied by significant changes in the expression of the coactivators CREB-binding protein, p300, steroid receptor coactivator 1, or the corepressors nuclear receptor corepressor and silence mediator for retinoid and thyroid hormone receptors. We critically evaluated the effects of selective PPAR ligands and a synthetic fatty acid analog, tetradecylthioacetic acid. Tetradecylthioacetic acid activated all human PPAR subtypes in the ranking order PPAR >> PPAR > PPAR. All selective PPAR ligands marginally induced transglutaminase-1 expression with the PPAR-selective ligand L165041 being the most potent. The PPAR- and PPAR-selective ligands Wy14643 and BRL49653 had negligible effect on involucrin expression, whereas a dose-dependent induction was observed with L165041. Simultaneous addition of L165041 and BRL49653 synergistically induced strong involucrin expression. Additionally, L165041 potently induced CD36 mRNA expression. Administration of tetradecylthioacetic acid resulted in a dramatic decrease in proliferation and a robust upregulation of the expression of involucrin and transglutaminase. Our results indicate that tetradecylthioacetic acid may affect keratinocyte gene expression and differentiation via PPAR-dependent and PPAR-independent pathways, and that the latter play an important role.Keywords: CD36, FAT, involucrin, MAPK, PPARs, transglutaminase-1
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The recently reported cases of skin lesions discussed here were produced under conditions which indicate a lack of some growth factor. In no case were conditions such that uncomplicated fat-deficiency could result. It would be impossible, therefore, for these rats to respond to small doses of unsaturated fats. An adequate supply of all water soluble growth factors must be fed if the typical fat deficiency results are to be obtained. Growth should approximate that given by the daily consumption of 0.65 gm. or more of high grade dried yeast.
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The purpose of this study was to investigate whether fish oil and/or corn oil had a beneficial effect on the clinical state of atopic dermatitis, and to evaluate the dietary intake of nutrients in this group of patients. In a double-blind, multicentre study lasting 4 months, during wintertime, 145 patients with moderate to severe atopic dermatitis were randomly assigned to receive either 6 g/day of concentrated n-3 fatty acids, or an isoenergetic amount of corn oil. As local treatment, only an emollient cream or hydrocortisone cream was allowed. The fatty acid pattern in serum phospholipids, and the dietary intake of nutrients were monitored in a subgroup of patients, and the results were compared with a group of patients with psoriasis. The overall clinical score, as evaluated by the physicians, improved during the trial by 30% in the fish oil (P < 0.001) and 24% in the corn oil group (P < 0.001). This was also consistent with the results from a selected skin area, and it was further confirmed by the total subjective clinical score reported by the patients. There were no significant differences in the clinical scores between the two groups at baseline, and at the end of the study. In the fish oil group, the amount of n-3 fatty acids in serum phospholipids was significantly increased at the end of the trial, compared with pretreatment values (P < 0.001), whereas the level of n-6 fatty acids was decreased (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The family of transcription factors termed peroxisome proliferator-activated receptors (PPARs) has recently been the focus of much interest for their possible role in the regulation of inflammation and immune responses. PPARalpha and PPARgamma have been implicated in the regulation of macrophage and endothelial cell inflammatory responses. Although PPAR activation has generally been shown to have anti-inflammatory effects, opposite effects have been noted, and results often appear to depend on the ligands being used and the inflammatory parameters being measured. Recently, my laboratory and others have described a role for PPARgamma in the responses of T lymphocytes. Ligands for PPARgamma have been found to inhibit proliferation of activated T cells, and this appears to involve inhibition of IL-2 secretion and/or the induction of apoptosis. However, one problem in the interpretation of many of the studies of PPARgamma, inflammation, and immunity is that ligands thought to be specific for PPARgamma may have regulatory effects on inflammatory parameters that are PPARgamma-independent. Future studies of the role of the PPARs in inflammatory and immune responses should include further studies of T cells, T-cell subsets, and dendritic cells but will have to re-examine the issue of PPAR specificity of the ligands being used. This may require further knockout studies and technology, together with the identification of endogenous and perhaps more specific synthetic PPAR ligands
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The epidermal sphingolipids from rats maintained on either a rat stock diet or a fat-free diet have been analyzed. Thin-layer Chromatographic analyses have revealed glucosylceramides, acylglucosylceramides and four fractions of ceramides, one of which proved to be an acylceramide. The relative amounts of the glucosylceramides, acylglucosylceramides and acylceramides were increased in the essential fatty acid-deficient epidermis while one ceramide fraction was diminished. The other two ceramide fractions remained unchanged. The acylceramides and acylglucosylceramides from normal rat epidermis both contained long-chain ω-hydroxy acids in amide linkage to sphingosine bases and high proportions of linoleic acid in ester linkage. The linoleate, which is known to be crucial for the formation and maintenance of the epidermal water barrier, was replaced by oleate in the essential fatty acid-deficient rats.
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Linoleate-rich O-acylglucosylceramides and acylceramides are thought to be of major significance for the physical structure and function of the epidermal permeability barrier. In the present investigation, the effects of a linoleate-free diet on O-acylsphingolipids and their associated functions were investigated. Starting at 5 days of age, male pigs were fed diets containing 12% of either lard or hydrogenated coconut oil. Transepidermal water loss was measured with an electrolytic water analyzer at weekly intervals. Pigs were killed at intervals, and epidermal lipids were isolated and analyzed. Fatty acid compositions were determined by gas-liquid chromatography (GLC). Within 2–3 weeks, pigs on the diet containing coconut oil began to display biochemical and physiological symptoms of essential fatty acid deficiency. Within 2 months, this group had extremely scaly skin and transepidermal water loss was elevated to five times that of controls. The progressive increase in transepidermal water loss correlated with replacement of linoleate by oleate in both acylceramide and acylglucosylceramide. The formation of lamellar granules and intercellular lipid sheets in the stratum corneum was not impaired in essential fatty acid deficiency as judged by electron microscopy. These results suggest that the linoleic acid normally found in the O-acylsphingolipids is not essential for formation of the epidermal membrane system. Rather, it appears that the nature of the ester-linked fatty acid in the O-acylsphingolipids regulates the permeability of this membrane system.
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To review the current reproductive advances in insulin-sensitizing agents for treatment of polycystic ovary syndrome patients. To date, among insulin-sensitizing drugs, only metformin should be used to improve reproductive function in well selected polycystic ovary syndrome patients. Preliminary data seem to show beneficial effects of thiazolidinediones in improving metabolic and hormonal patterns and in restoring regular menses. The use of insulin-sensitizing drugs offers a new perspective for the treatment of polycystic ovary syndrome-related reproductive disorders. However, further data are needed before we can draw definitive conclusions regarding their clinical role.
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Research from the 1930s to the 1950s established that a deficit of n-6 essential fatty acids (EFAs) leads to an inflammatory skin condition in both animals and humans. In a common inherited skin condition, atopic dermatitis (eczema), there was evidence of low blood EFA concentrations and of a therapeutic response to exceptionally high doses of linoleic acid. More recently, it has been established that there is no deficit of linoleic acid in atopic eczema. Concentrations of linoleic acid instead tend to be elevated in blood, milk, and adipose tissue of patients with atopic eczema, whereas concentrations of linoleic acid metabolites are substantially reduced. This suggests reduced conversion of linoleic acid to gamma-linolenic acid (GLA). In most but not all studies, administration of GLA has been found to improve the clinically assessed skin condition, the objectively assessed skin roughness, and the elevated blood catecholamine concentrations of patients with atopic eczema. Atopic eczema may be a minor inherited abnormality of EFA metabolism.
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Peroxisome proliferator activated receptor gamma (PPARγ) is a ligand-dependent transcription factor and a member of the nuclear receptor superfamily. Acting as sensors of hormones, vitamins, endogenous metabolites and xenobiotic compounds, the nuclear receptors control the expression of a very large number of genes. PPARγ has been known for some time to regulate adipocyte differentiation, fatty acid storage and glucose metabolism, and is a target of anti-diabetic drugs. More recently, PPARγ has been recognized as playing a fundamentally important role in the immune response through its ability to inhibit the expression of inflammatory cytokines and to direct the differentiation of immune cells towards anti-inflammatory phenotypes. A feature of PPARγ is the structural diversity of its ligands, which encompass endogenous metabolites, dietary compounds and synthetic drugs. The high and increasing incidence of inflammatory and allergic disease, coupled with encouraging results from recent clinical trials, suggest that natural PPARγ agonists found in foods may be beneficial to human health by acting as anti-inflammatory molecules. PPARγ is therefore not only a target of the pharmaceutical industry, but also of great potential interest to the food industry, since it is activated by several natural dietary constituents. The prospects for dietary intervention in inflammatory disease have improved somewhat over the last few years, and are reviewed here.
Article
The authors assessed the efficacy of a ceramide-dominant, triple-lipid barrier repair formulation (EpiCeram), which designed to correct the lipid-biochemical abnormalities in atopic dermatitis (AD) in comparison to fluticasone propionate cream. In a five-center, investigator-blinded, randomized trial, EpiCeram was compared to fluticasone (Cutivate) cream in 121 patients with moderate-to-severe AD. Primary outcome measures were: 1) reduction in disease severity, assessed as SCORAD (Severity Scoring for Atopic Dermatitis) scores; 2) improvement in pruritus; and 3) improvements in sleep habits. EpiCeram reduced clinical disease severity, decreased pruritus and improved sleep habits both 14 and 28 days after initiation of therapy. Although the fluticasone-treated group showed significantly greater improvement at 14 days, SCORAD, pruritus and sleep habit scores for EpiCeram did not differ significantly from the fluticasone-treated group by 28 days. The ceramide-dominant, physiological-lipid based formulation could represent an effective stand-alone or ancillary therapy for many pediatric patients with AD.
Article
To evaluate the efficacy and safety of combination therapy with acitretin and pioglitazone hydrochloride in patients with moderate to severe chronic plaque-type psoriasis. Randomized, double-blind, placebo-controlled clinical trial. A tertiary care referral hospital. Patients The study included patients of either sex (age range, 18-65 years) with moderate to severe chronic plaque-type psoriasis. Patients were excluded if they were of child-bearing potential or if they had impaired liver or renal function, hyperlipidemia, diabetes mellitus, coronary artery disease, or a body mass index greater than 30 (calculated as weight in kilograms divided by height in meters squared). Of the 62 patients screened, 41 were randomly assigned to 2 groups: 22 to an acitretin (25 mg) plus placebo group and 19 to an acitretin (25 mg) plus pioglitazone hydrochloride (15 mg) group. Main Outcome Measure Change in Psoriasis Area and Severity Index score between the 2 groups from baseline to 12 weeks. After 12 weeks of therapy, the percentage of reduction in the Psoriasis Area and Severity Index score was 64.2% in the acitretin plus pioglitazone group and 51.7% in the acitretin plus placebo group. The majority of the adverse events were mild to moderate except for 1 possibly unrelated episode of acute myocardial infarction in a 49-year-old woman in the acitretin plus placebo group. Pioglitazone has a potential beneficial antipsoriatic effect and may provide a convenient, efficacious, and relatively safe option to combine with acitretin, although further studies are needed. Trial Registration clinicaltrials.gov Identifier: NCT00395941.
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Peroxisome proliferator-activated receptors (PPARs) are drug targets for several perturbations of metabolic syndrome, defined as the coexistence of obesity, hyperglycemia, hypertension, and hyper/dyslipidemia. In this study, PPAR activation by oregano (e.g., Origanum vulgare) and its components was tested. Oregano extracts bind but do not transactivate PPARgamma, and binding affinity differs among different oregano extracts. The extracts contain PPARgamma antagonists (e.g., quer