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Wasabi leaf supplementation had antioxidant, anti-glycation, and improved skin melanin, spot and moisture
Abstract
The beauty of nature led to the rise of the human medical cosmetic industry, which gave a breed between beauty care products and pharmaceutical, medical-stressed skin care and beauty care products. However, the current clinical research on wasabi leaves and skin is still unclear. The purpose of this study was to investigate the wasabi by-product-wasabi leaves, for antioxidant, anti-glycation and whitening effects. This study used wasabi leaf extract treated in melanocytes, and examined melanin, inflammatory factors, advanced glycation end products (AGEs), and recruited subjects to take wasabi leaf extract beverage labeled 50 mL or a placebo drink daily for 8 weeks. The results showed that wasabi leaf extract can significantly inhibit tyrosinase activity by 24 %, decrease melanin content by 21 %, decrease IL-8 gene expression by 74.2 % and inhibit the AGEs formation by 59 % compared to the control group in vitro. In clinical trial, wasabi leaf extract significantly increased total antioxidant capacity by 7.9 %, and decreased AGEs by 5.6 %, and decreased skin melanin, spots, deep spots by 4.0 %, 3.2 %, 4.2 %, increased skin moisture by 6.6 % compared to placebo group. The wasabi leaf extract decreased tyrosinase activity, melanin content, AGEs formation in vitro, and improved skin condition in clinical trial. The wasabi leaves could be regarded as an unexplored natural source of bioactive ingredients and applied for the development of related value-added products.
... 10 A recent clinical trial report showed that the wasabi extract decreased tyrosinase activity and melanin content and suppressed in vitro AGEs formation while improving skin conditions. 31 BG has the potential to serve as an alternative solvent for plant extracts, as it is widely used in cosmetic and pharmaceutical preparations without being removed from the final extract. In addition, it is categorized as a safe chemical by the United States FDA. ...
In this study, gold nanoparticles with Eutrema japonicum (AuNPs-E.j.) were synthesized using the butylene glycol extract of the plant’s grated stem and Au(III) chloride trihydrate solution. The primary characterization of...
... Experimental and clinical studies have demonstrated the effects of wasabi leaves on the skin. For example, wasabi leaf extract was shown to decrease tyrosinase activity, melanin content, and formation of advanced glycation end products in vitro and to improve skin condition in a clinical trial [23]. ...
Hexaraphane (6-methylsulfinylhexyl isothiocyanate; 6-MSITC) is an isothiocyanate present in the rhizomes and roots of wasabi (Eutrema japonicum (Miq.) Kiudz.). It is known to induce detoxifying and antioxidant enzymes by activating the Keap1-Nrf2 system, ameliorating oxidative damage in the body. Hexaraphane was shown to inhibit brain damage and improve dementia symptoms in Alzheimer’s model mice. Moreover, in two randomized controlled trials conducted on middle-aged and elderly subjects, the extract powder “Wasabi sulfinyl™” containing 0.8% hexaraphane improved memory, attention, and judgment. In a clinical study of fifteen patients with chronic fatigue syndrome, treatment with Wasabi sulfinyl ™ for 3 months improved brain fog and other symptoms.
The use of biomass in cosmetics is a growing trend, driven by an increasing demand for sustainable and environmentally friendly products. Biomass, derived from a range of renewable resources, offers numerous benefits for skin care due to its natural properties. This review highlights recent research advancements, current applications, and future prospects of biomass‐based cosmetics. While these products are gaining popularity for their eco‐friendly nature, the industry faces several challenges. One key issue is ensuring the sustainability of biomass sourcing, as overharvesting could lead to environmental degradation. Additionally, the lack of standard regulations and certifications for biomass‐based products poses a challenge to consumer confidence and product transparency. Despite these promising developments, safety and toxicity considerations must be addressed, particularly regarding the long‐term use of natural substances in cosmetics. Notably, this review provides a comparative examination of plant‐, wood‐, and waste‐sourced biomass, spotlighting novel extraction and formulation strategies that balance efficacy with environmental stewardship, an approach that distinguishes it from prior reviews focused on single‐source biomass. By linking fundamental research findings to emerging standards, the review offers fresh insights into how sustainability, regulatory measures, and consumer trust can jointly shape a more robust future for eco‐conscious beauty solutions.
The present study aimed to investigate the effects of (R)-(−)-1-isothiocyanato-6-(methylsulfinyl)-hexane [(R)-6-HITC], the major isothiocyanate present in wasabi, in an ex vivo model of inflammation using lipopolysaccharide-stimulated murine peritoneal macrophages. (R)-6-HITC improved the immune response and mitigated oxidative stress, which involved suppression of reactive oxygen species, nitric oxide, and pro-inflammatory cytokines (IL-1β, IL-6, IL-17, IL-18, and TNF-α) production and downregulation of pro-inflammatory enzymes such as inducible nitric oxide synthase, COX-2, and mPGES-1. In addition, (R)-6-HITC was able to activate the Nrf2/HO-1 axis while simultaneously inhibiting key signaling pathways, including JAK2/STAT3, mitogen-activated protein kinases, and canonical and noncanonical inflammasome pathways, orchestrating its potent immunomodulatory effects. Collectively, these findings demonstrate the potential of (R)-6-HITC as a promising nutraceutical for the management of immuno-inflammatory diseases and justify the need for further in vivo validation studies.
Natural plant extracts have gained significant attention in research due to their low toxicity, and potent antioxidant, and anti-aging properties. The present study investigated the phytochemical composition of a fermented rose extract (FRE), and evaluated its antioxidant, skin whitening, and anti-aging activities in vitro. The results showed that the FRE was rich in polyphenols and flavonoids. A total of 13 major compounds were identified by Liquid Chromatography-Mass Spectrometry (LC-MS), with astragalin as the primary component. In vitro, analysis of antioxidant activity showed that FRE effectively eliminated 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals and dose-dependent reduced intracellular reactive oxygen species (ROS) levels. The FRE dose-dependent inhibited tyrosinase, collagenase, and hyaluronidase activity, reduced intracellular melanin synthesis, up-regulated the expression of collagen type I alpha 1 (COL1A1) and collagen type III alpha 1 (COL3A1), and down-regulated matrix metalloproteinases (MMPs) expression. Additionally, treatment with FRE significantly downregulated the expression of mitogen-activated protein kinase 1 (MAPK1), suggesting that FRE may modulate MAPK signaling pathways for skin anti-aging.
In clinical settings, although Psoriasis Area and Severity Index (PASI) scoring system can provide a quick visual assessment of the severity of psoriasis vulgaris, there is still a strong demand for higher efficiency and accuracy in quantifying the inflammation status of psoriatic lesions. Currently, there are already commercial systems, such as the Courage + Khazaka Corneometer and Mexameter that measure skin capacitance and optical reflectance, for conveniently quantifying the status of skin barrier function and erythema of skin. Despite numerous comparisons of the Courage + Khazaka system with the PASI scoring system, they are rarely compared on parity with diffuse reflectance spectroscopy (DRS) based systems. In this study, we employed a custom-built DRS system shown to be able to determine the skin water-protein binding status and the hemoglobin concentration, and we performed cross-validation of the DRS measurement results with the readings derived from the Corneometer and Mexameter as well as a portion of the PASI scores. Our results revealed that the erythema readings from the Mexameter were a good representation of skin oxygenated hemoglobin but not the deoxygenated hemoglobin. On the other hand, the dermatologists recruited in this study were inclined to rate higher scores on the “erythema” category as skin’s deoxygenated hemoglobin level was higher. Thus, the Mexameter derived erythema readings may not be coherent with the PASI erythema scores. Further, the Corneometer derived skin capacitance readings were well correlated to the PASI “desquamation” and “thickness” scores, while the PASI “desquamation” evaluation was a dominating factor contributing to the DRS deduced water-protein binding status. We conclude that the DRS method could be a valuable addition to existing skin capacitance/reflectance measurement systems and the PASI scoring system toward achieving a more efficient and objective clinical psoriasis vulgaris severity evaluation.
Nowadays, much attention is paid to issues such as ecology and sustainability. Many consumers choose "green cosmetics", which are environmentally friendly creams, makeup, and beauty products, hoping that they are not harmful to health and reduce pollution. Moreover, the repeated mini-lock downs during the COVID-19 pandemic have fueled the awareness that body beauty is linked to well-being, both external and internal. As a result, consumer preferences for makeup have declined, while those for skincare products have increased. Nutricosmetics, which combines the benefits derived from food supplementation with the advantages of cosmetic treatments to improve the beauty of our body, respond to the new market demands. Food chemistry and cosmetic chemistry come together to promote both inside and outside well-being. A nutricosmetic optimizes the intake of nutritional microelements to meet the needs of the skin and skin appendages, improving their conditions and delaying aging, thus helping to protect the skin from the aging action of environmental factors. Numerous studies in the literature show a significant correlation between the adequate intake of these supplements, improved skin quality (both aesthetic and histological), and the acceleration of wound-healing. This review revised the main foods and bioactive molecules used in nutricosmetic formulations, their cosmetic effects, and the analytical techniques that allow the dosage of the active ingredients in the food.
Skin aging is a natural, unavoidable, and complex process caused by oxidative stress. As a consequence, it leads to an increase in the activation of extracellular matrix disruption enzymes and DNA damage. The search for natural sources that inhibit these mechanisms can be a good approach to prevent skin aging. The purpose of our study was to evaluate the composition of flavonoids and phenolic acids in the extracts obtained from the flowers, roots, and leaves of Eutrema japonicum cultivated in Poland. Then, the resultant extracts were subjected to an assessment of antioxidant, anti-collagenase, anti-elastase, anti-hyaluronidase, antibacterial, and cytotoxic properties. It was demonstrated that the extract from the flowers had the highest content of flavonoid glycosides (17.15 mg/g DE). This extract showed the greatest antioxidant, anti-collagenase, anti-elastase, and anti-hyaluronidase activities compared to the other samples. Importantly, the collagenase inhibitory activity of this extract (93.34% ± 0.77%) was better than that of positive control epigallocatechin gallate (88.49% ± 0.45%). An undeniable advantage of this extract was also to possess moderate antibacterial properties and no cytotoxicity towards normal human skin fibroblasts. Our results suggest that extracts from E. japonicum flowers may be considered as a promising antiaging compound for applications in cosmetic formulations.
Chronic wounds are a public health problem worldwide, especially those related to diabetes. Besides being an enormous burden to patients, it challenges wound care professionals and causes a great financial cost to health system. Considering the absence of effective treatments for chronic wounds, our aim was to better understand the pathophysiology of tissue repair in diabetes in order to find alternative strategies to accelerate wound healing. Nucleotides have been described as extracellular signaling molecules in different inflammatory processes, including tissue repair. Adenosine-5’-diphosphate (ADP) plays important roles in vascular and cellular response and is immediately released after tissue injury, mainly from platelets. However, despite the well described effect on platelet aggregation during inflammation and injury, little is known about the role of ADP on the multiple steps of tissue repair, particularly in skin wounds. Therefore, we used the full-thickness excisional wound model to evaluate the effect of local ADP application in wounds of diabetic mice. ADP accelerated cutaneous wound healing, improved new tissue formation, and increased both collagen deposition and transforming growth factor-β (TGF-β) production in the wound. These effects were mediated by P2Y12 receptor activation since they were inhibited by Clopidogrel (Clop) treatment, a P2Y12 receptor antagonist. Furthermore, P2Y1 receptor antagonist also blocked ADP-induced wound closure until day 7, suggesting its involvement early in repair process. Interestingly, ADP treatment increased the expression of P2Y12 and P2Y1 receptors in the wound. In parallel, ADP reduced reactive oxygen species (ROS) formation and tumor necrosis factor-α (TNF-α) levels, while increased IL-13 levels in the skin. Also, ADP increased the counts of neutrophils, eosinophils, mast cells, and gamma delta (γδ) T cells (Vγ4⁺ and Vγ5⁺ cells subtypes of γδ⁺ T cells), although reduced regulatory T (Tregs) cells in the lesion. In accordance, ADP increased fibroblast proliferation and migration, myofibroblast differentiation, and keratinocyte proliferation. In conclusion, we provide strong evidence that ADP acts as a pro-resolution mediator in diabetes-associated skin wounds and is a promising intervention target for this worldwide problem.
Aims
Non-invasively assessed skin autofluorescence (SAF) measures advanced glycation endproducts (AGEs) in the dermis. SAF correlates with dermal AGEs in Caucasians and Asians, but studies in dark-skinned subjects are lacking. In this pilot we aimed to assess whether SAF signal is representative of intrinsic fluorescence (IF) and AGE accumulation in dark skin.
Methods
Skin biopsies were obtained in 12 dark-skinned subjects (6 healthy subjects, median age 22 years; 6 diabetes mellitus (DM) subjects, 65 years). SAF was measured with the AGE Reader, IF using confocal microscopy, and AGE distribution with specific antibodies. CML and MG-H1 were quantified with UPLC-MS/MS and pentosidine with HPLC and fluorescent detection.
Results
SAF correlated with IF from the dermis (405nm, r = 0.58, p < 0.05), but not with CML (r = 0.54, p = 0.07). CML correlated with IF from the dermis (405nm, r = 0.90, p < 0.01). UV reflectance and the coefficient of variation of SAF were negatively correlated (r = -0.80, p < 0.01). CML and MG-H1 were predominantly present around blood vessels, in collagen and fibroblasts in the dermis.
Conclusion
This proof of concept study is the first to compare non-invasive SAF with AGE levels measured in skin biopsies in dark-skinned subjects. SAF did not correlate with individual AGEs from biopsies, but was associated with IF. However, the intra-individual variance was high, limiting its application in dark-skinned subjects on an individual basis.
Background
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to ALT ratio (AST/ALT ratio) have been shown to be related to non-alcoholic fatty liver disease or insulin resistance, which was associated with chronic kidney disease (CKD). However, it is unclear whether ALT and AST/ALT ratio are associated with CKD. In this study, we examined the relationship of ALT and AST/ALT ratio to CKD among middle-aged females in Japan.
Methods
The present study included 29,133 women aged 40 to 64 years who had an annual health checkup in Japan during April 2013 to March 2014. Venous blood samples were collected to measure ALT, AST, gamma-glutamyltransferase (GGT), and creatinine levels. In accordance with previous studies, ALT > 40 U/L and GGT > 50 U/L were determined as elevated, AST/ALT ratio < 1 was regarded as low, and CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m² and/or proteinuria. Logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for CKD.
Results
“Elevated ALT and elevated GGT” and “elevated ALT and non-elevated GGT” significantly increased the OR for CKD when compared with “non-elevated ALT and non-elevated GGT” (OR: 2.56, 95% CI: 2.10–3.12 and OR: 2.24, 95% CI: 1.81–2.77). Compared with “AST/ALT ratio ≥ 1 and non-elevated GGT”, “AST/ALT ratio < 1 and elevated GGT” and “AST/ALT ratio < 1 and non-elevated GGT” significantly increased the OR for CKD (OR: 2.73, 95% CI: 2.36–3.15 and OR: 1.68, 95% CI: 1.52–1.87). These findings still remained after adjustment for confounders.
Conclusions
Elevated ALT was associated with CKD regardless of GGT elevation. Moreover, low AST/ALT ratio was also associated with CKD independent of GGT elevation.
N ⁶ -methyladenosine is the most prominent RNA modification in mammals. Here we study mouse skin embryogenesis to tackle m6A’s functions and physiological importance. We first landscape the m6A modifications on skin epithelial progenitor mRNAs. Contrasting with in vivo ribosomal profiling, we unearth a correlation between m6A-modification in coding sequences and enhanced translation, particularly of key morphogenetic signaling pathways. Tapping physiological relevance, we show that m6A loss profoundly alters these cues and perturbs cellular fate choices and tissue architecture in all skin lineages. By single-cell transcriptomics and bioinformatics, both signaling and canonical translation pathways show significant downregulation after m6A loss. Interestingly, however, many highly m6A-modified mRNAs are markedly upregulated upon m6A loss, and they encode RNA-methylation, RNA-processing and RNA-metabolism factors. Together, our findings suggest that m6A functions to enhance translation of key morphogenetic regulators, while also destabilizing sentinel mRNAs that are primed to activate rescue pathways when m6A levels drop.
Glucosinolates (GSLs) are sulfur-containing defense metabolites produced in the Brassicales, including the model plant Arabidopsis (Arabidopsis thaliana). Previous work suggests that specific GSLs may function as signals to provide direct feedback regulation within the plant to calibrate defense and growth, including allyl-GSL, a defense metabolite and one of the most widespread GSLs in Brassicaceae that has also been associated with growth inhibition. Here we show that at least three separate potential catabolic products of allyl-GSL or closely related compounds affect growth and development by altering different mechanisms influencing plant development. Two of the catabolites, raphanusamic acid and 3-butenoic acid, differentially affect processes downstream of the auxin signaling cascade. Another catabolite, acrylic acid, affects meristem development by influencing the progression of the cell cycle. These independent signaling events propagated by the different catabolites enable the plant to execute a specific response that is optimal to any given environment.
Dietary intake and obesity can alter the composition of the gut microbiota thereby affecting the health of the host. It is unclear if intake of glucosinolate-containing cruciferous vegetables alters the composition of the gut microbiota in obesity. The aim of this study was to compare the gut microbiota composition between six diet-induced obese rats receiving Wasabia japonica (wasabi) supplementation (5% (w/w)) for eight weeks and six control diet-induced obese rats by 16S rRNA amplicon sequencing. Supplementation with wasabi reduced beta but not alpha diversity in obese rats and was associated with increased abundance of the bacterial genera Allobaculum, Bifidobacterium and Unclassified S24-7 and decreased abundance of Unclassified Enterobacteriaceae, Unclassified Ruminococcaceae, Unclassified Lachnospiraceae and Unclassified Desulfovibrionaceae. Supplementation with wasabi is predicted to result in less bacterial biosynthesis of fatty acids and phospholipids, which may lead to improved host lipid markers in diet-induced obese rats.
Purpose
The oxidative stress plays a key role in the initiation, propagation, and development of the complications of type 2 diabetes mellitus (T2DM). This trial aimed to evaluate the effects of resistant dextrin as a prebiotic on the cardiometabolic risk factors and the status of oxidative stress in patients with T2DM.
Methods
Sixty-five female subjects with T2DM were assigned to either the intervention (n = 33) or control (n = 32) groups receiving 10 g/day of resistant dextrin or placebo, respectively, for 8 weeks. Fasting blood samples were collected at baseline and post-intervention to determine the serum levels of glycemic indices, lipid profile, atherogenic indices, and soluble receptor for AGEs (sRAGE), carboxymethyl lysine (CML), pentosidine, malondialdehyde (MDA), 8-iso-prostaglandin F2α (8-iso-PGF2α), total antioxidant capacity (TAC), antioxidant enzymes activity, and uric acid. Data were analyzed using SPSS software 17. Paired, unpaired Student’s t tests, and analysis of covariance were used to compare the quantitative variables.
Results
Resistant dextrin caused a significant decrease in FPG (− 17.43 mg/dl, 9.80%), TG (− 40.25 mg/dl, 23.01%), TC/HDL (− 0.80, 21.87%), LDL-c/HDL-c (− 0.80, 17.85%), Atherogenic index (− 0.40, 15.80%), LPS (− 6.5 EU/ml, 23.40%) and hs-CRP (− 8.02 ng/ml, 54.00%), MDA (− 1.21 nmol/mL, 25.58%), CML (− 93.40 ng/ml, 26.30%), 8-iso-PGF2α (− 4.65 pg/ml, 15.00%), and a significant increase in TAC (0.33 mmol/L, 36.25%) and s-RAGE (2.10 ng/ml, 28.90%) in the intervention group compared with the control group. No significant changes were observed in glycosylated hemoglobin, total cholesterol, LDL-c, HDL-c, superoxide dismutase, glutathione peroxidase and catalase, pentosidine, and uric acid in the intervention group compared with the control group.
Conclusions
Supplementation with resistant dextrin may improve the advanced glycation end-products, sRAGE, and cardiometabolic risk factors in women with type 2 diabetes mellitus.
The skin is the main barrier that protects us against environmental stressors (physical, chemical, and biological). These stressors, combined with internal factors, are responsible for cutaneous aging. Furthermore, they negatively affect the skin and increase the risk of cutaneous diseases, particularly skin cancer. This review addresses the impact of environmental stressors on skin aging, especially those related to general and specific external factors (lifestyle, occupation, pollutants, and light exposure). More specifically, we have evaluated ambient air pollution, household air pollutants from non-combustion sources, and exposure to light (ultraviolet radiation and blue and red light). We approach the molecular pathways involved in skin aging and pathology as a result of exposure to these external environmental stressors. Finally, we reflect on how components of environmental stress can interact with ultraviolet radiation to cause cell damage and the critical importance of knowing the mechanisms to develop new therapies to maintain the skin without damage in old age and to repair its diseases.
Purpose
Current pharmacotherapy for persistent pain related to neuropathy or articular diseases is unsatisfactory, due to the large number of unresponsive patients and side effects. Isothiocyanates (ITCs) are a class of natural or synthetic compounds characterized by the general formula R–NCS. ITCs show antihyperalgesic effects in models of central and peripheral nervous tissue injury and anti-inflammatory properties. The pharmacodynamics are strictly related to the release of the gasotransmitter hydrogen sulfide (H2S) from their moiety. In particular, phenyl ITC (PITC) and 3-carboxyphenyl ITC (3C-PITC) exhibit interesting slow H2S-release properties suitable for treating painful pathology. The aim of the present work was to evaluate the efficacy of PITC and 3C-PITC against mechanical hyperalgesia and spontaneous pain induced by nerve injury and osteoarthritis.
Methods
Nerve injury and osteoarthritis were induced in rats by ligation of the sciatic nerve (chronic constriction injury) and intra-articular injection of monoiodoacetate, respectively. Behavioral tests were performed 14 days after damage induction.
Results
Single subcutaneous administrations of PITC, 3C-PITC (4.43 and 13.31 µmol kg⁻¹, respectively) were able to completely reverse hypersensitivity to noxious stimuli in both models of neuropathic and osteoarticular pain. The effect of ITCs was compared with that of NaHS, the prototypical H2S donor, showing similar efficacy and higher potency. ITCs and NaHS also reduced spontaneous pain.
Conclusion
ITCs offer a promising novel approach to counteract persistent, drug-resistant painful pathology.
ABSTRACT
Background and Objectives: Coronary artery disease (CAD) is a major cause of death
worldwide. Chronic stable angina (CSA) is the primary sign of CAD. Oxidative stress and
inflammation play a substantial role in pathogenesis and progression of CAD. The aim of
this study was to investigate the effects of oral administration of powdered Melissa
officinalis (MO) on biomarkers of oxidative stress, inflammation, and lipid profile in
patients with CSA. Methods and Study Design: A randomized, double-blind,
placebo-controlled clinical trial was performed in 80 patients with CSA. The subjects were
randomly assigned to obtain either oral MO 3 g/d (n=40) or placebo (n=40) for eight weeks.
Anthropometric indices, biomarkers of oxidative stress, inflammation, and lipid profile
were evaluated at baseline and post-intervention. Results: The mean serum concentrations
of triglycerides, total-cholesterol, LDL-cholesterol, and malondialdehyde (MDA), and high
sensitive C-Reactive Protein (hs-CRP) were lower in the intervention group compared with
placebo (p<0.01) post intervention. Moreover, the mean serum concentration of
paraxonase 1 (PNO1) and HDL-c were higher (p<0.001) in the intervention group
compared with the control group. Conclusion: Oral MO supplementation improves the
lipid profile, MDA, hs-CRP, and PNO1 in patients with CSA.
Key Words: Melissa officinalis, coronary artery disease, oxidative stress, paraxonase
1, lipid profile
The demand for rapid methods for the quantification of pathogens is increasing. Among these methods, those based on nucleic acids amplification (quantitative PCRs) are the most widespread worldwide. Together with the qPCR, a new approach named digital PCR (dPCR), has rapidly gained importance. The aim of our study was to compare the results obtained using two different dPCR systems and one qPCR in the quantification of three different bacterial pathogens: Listeria monocytogenes, Francisella tularensis, and Mycobacterium avium subsp. paratuberculosis. For this purpose, three pre-existing qPCRs were used, while the same primers and probes, as well as PCR conditions, were transferred to two different dPCR systems: the QX200 (Bio-Rad) and the Quant Studio 3D (Applied Biosystems). The limits of detection and limits of quantification for all pathogens, and all PCR approaches applied, were determined using genomic pure DNAs. The quantification of unknown decimal suspensions of the three bacteria obtained by the three different PCR approaches was compared through the Linear Regression and Bland and Altman analyses. Our results suggest that, both dPCRs are able to quantify the same amount of bacteria, while the comparison among dPCRs and qPCRs, showed both over and under-estimation of the bacteria present in the unknown suspensions. Our results showed qPCR over-estimated the amount of M. avium subsp. paratuberculosis and F. tularensis cells. On the contrary, qPCR, compared to QX200 dPCR, under-estimated the amount of L. monocytogenes cells. However, the maximum difference among PCRs approaches was <0.5 Log10, while cultural methods underestimated the number of bacteria by one to two Log10 for Francisella tularensis and Mycobacterium avium subsp. paratuberculosis. On the other hand, cultural and PCRs methods quantified the same amount of bacteria for L. monocytogenes, suggesting for this last pathogen, PCRs approaches can be considered as a valid alternative to the cultural ones.
The relationship between Helicobacter pylori infection and gastric cancer associated with stomach lesions has been reported. Improvement of the adverse effects induced by H. pylori is required for human health. It has been reported that wasabi (Wasabia japonica Matsum) leaves have various effects on bacteria and mammals. In this study, the effect was examined of wasabi leaf extract and allyl isothiocyanate (AIT), which is a main functional component of wasabi, on stomach lesions in Mongolian gerbils infected with H. pylori. After the gerbils infected with H. pylori were orally administrated with wasabi leaf extract and AIT for two weeks, colony forming units (CFU) of H. pylori, the degree of gastric mucosal erosion, and petechial hemorrhage in the stomachs of the gerbils were evaluated. Wasabi leaf extract and AIT exhibited a decreasing tendency of CFU in the stomachs. The degree of gastric mucosal erosion and petechial hemorrhage were significantly decreased by the intake of wasabi leaf extract and AIT. Wasabi leaf extract and AIT did not affect body weight, dietary intake, water intake, and the pH of the stomach. From these results, wasabi leaves and AIT may provide a natural remedy for stomach lesions induced by H. pylori.
Melanogenesis is a process to synthesize melanin, which is a primary responsible for the pigmentation of human skin, eye and hair. Although numerous enzymatic catalyzed and chemical reactions are involved in melanogenesis process, the enzymes such as tyrosinase and tyrosinase-related protein-1 (TRP-1) and TRP-2 played a major role in melanin synthesis. Specifically, tyrosinase is a key enzyme, which catalyzes a rate-limiting step of the melanin synthesis, and the downregulation of tyrosinase is the most prominent approach for the development of melanogenesis inhibitors. Therefore, numerous inhibitors that target tyrosinase have been developed in recent years. The review focuses on the recent discovery of tyrosinase inhibitors that are directly involved in the inhibition of tyrosinase catalytic activity and functionality from all sources, including laboratory synthetic methods, natural products, virtual screening and structure-based molecular docking studies.
Background
The aims of this paper are: 1) to present the My Skin questionnaire, 2) to report the preliminary results of a study on the emotional-cognitive skin representation, and 3) to encourage dermatologists and other specialists to use the My Skin questionnaire in their research. The inspiration for a new tool measuring the emotional and cognitive representation of skin was the psychological conception of the ‘skin ego’.
Participants and procedure
My Skin, a self-questionnaire (MSQ), was used to measure the emotional and cognitive representation of an individual’s skin. It consists of two main scales: satisfaction with the skin condition (AB) and awareness of the biopsychosocial functions of the skin (C). The Body Esteem Scale, Body Self Questionnaire and Self-Esteem Scale were used to validate the MSQ. The participants were: healthy individuals (n = 343) and dermatology patients (psoriasis, vitiligo, juvenile acne, n = 84).
Results
The psychometric parameters are presented in this article. The internal consistency reliabilities for subscales are in the range of .75 and .95. This article also presents preliminary basic statistics for the skin representation of dermatology patients and healthy people.
Conclusions
My Skin questionnaire is a valid tool for assessing cognitive and emotional representation of skin and may be used in psychodermatology and esthetic dermatology to assess satisfaction with and awareness of skin.
The Cordyceps species have been widely used for treating various cancer diseases. Although the Cordyceps species have been widely known as an alternative anticancer remedy, which compounds are responsible for their anticancer activity is not fully understood. In this study, therefore, we examined the anticancer activity of 5 isolated compounds derived from the butanol fraction (Cb-BF) of Cordyceps bassiana. For this purpose, several cancer cell lines such as C6 glioma, MDA-MB-231, and A549 cells were employed and details of anticancer mechanism were further investigated. Of 5 compounds isolated by activity-guided fractionation from BF of Cb-EE, KTH-13, and 4-isopropyl-2,6-bis(1-phenylethyl)phenol, Cb-BF was found to be the most potent antiproliferative inhibitor of C6 glioma and MDA-MB-231 cell growth. KTH-13 treatment increased DNA laddering, upregulated the level of Annexin V positive cells, and altered morphological changes of C6 glioma and MDA-MB-231 cells. In addition, KTH-13 increased the levels of caspase 3, caspase 7, and caspase 9 cleaved forms as well as the protein level of Bax but not Bcl-2. It was also found that the phosphorylation of AKT and p85/PI3K was also clearly reduced by KTH-13 exposure. Therefore, our results suggest KTH-13 can act as a potent antiproliferative and apoptosis-inducing component from Cordyceps bassiana, contributing to the anticancer activity of this mushroom.
Type 2 diabetes mellitus (T2DM) is a very complex and multifactorial metabolic disease characterized by insulin resistance and β cell failure leading to elevated blood glucose levels. Hyperglycemia is suggested to be the main cause of diabetic complications, which not only decrease life quality and expectancy, but are also becoming a problem regarding the financial burden for health care systems. Therefore, and to counteract the continually increasing prevalence of diabetes, understanding the pathogenesis, the main risk factors, and the underlying molecular mechanisms may establish a basis for prevention and therapy. In this regard, research was performed revealing further evidence that oxidative stress has an important role in hyperglycemia-induced tissue injury as well as in early events relevant for the development of T2DM. The formation of advanced glycation end products (AGEs), a group of modified proteins and/or lipids with damaging potential, is one contributing factor. On the one hand it has been reported that AGEs increase reactive oxygen species formation and impair antioxidant systems, on the other hand the formation of some AGEs is induced per se under oxidative conditions. Thus, AGEs contribute at least partly to chronic stress conditions in diabetes. As AGEs are not only formed endogenously, but also derive from exogenous sources, i.e., food, they have been assumed as risk factors for T2DM. However, the role of AGEs in the pathogenesis of T2DM and diabetic complications-if they are causal or simply an effect-is only partly understood. This review will highlight the involvement of AGEs in the development and progression of T2DM and their role in diabetic complications.
The anti-obesity effects of a hot water extract from wasabi (Wasabia japonica Matsum.) leaves (WLE), without its specific pungent constituents, such as allyl-isothiocyanate, were investigated in high fat-diet induced mice. C57J/BL mice were fed a high-fat diet (control group) or a high-fat diet supplemented with 5% WLE (WLE group). Physical parameters and blood profiles were determined. Gene expression associated with lipid metabolism in liver and white adipose tissue were analyzed. After 120 days of feeding, significantly lower body weight gain, liver weight and epididymal white adipose tissue weight was observed in the WLE group compared to the control group. In liver gene expression within the WLE group, PPARα was significantly enhanced and SREBP-1c was significantly suppressed. Subsequent downstream genes controlled by these regulators were significantly suppressed. In epididymal white adipose tissue of the WLE group, expression of leptin, PPARγ, and C/EBPα were significantly suppressed and adiponectin was significantly enhanced. Acox, related to fatty acid oxidization in adipocytes, was also enhanced. Our results demonstrate that the WLE dietary supplement induces mild suppression of obesity in a high-fat diet induced mice, possibly due to suppression of lipid accumulation in liver and white adipose tissue.
UV radiation (UV) is classified as a "complete carcinogen" because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and molecularly linked to the three most common types of skin cancer, basal cell carcinoma, squamous cell carcinoma and malignant melanoma, which together affect more than a million Americans annually. Genetic factors also influence risk of UV-mediated skin disease. Polymorphisms of the melanocortin 1 receptor (MC1R) gene, in particular, correlate with fairness of skin, UV sensitivity, and enhanced cancer risk. We are interested in developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance.
6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously reported that 6-MSITC strongly suppresses cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokines, which are important factors that mediate inflammatory processes. Moreover, molecular analysis demonstrated that 6-MSITC blocks the expressions of these factors by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. Structure-activity relationships of 6-MSITC and its analogues containing an isothiocyanate group revealed that methylsulfinyl group and the length of alkyl chain of 6-MSITC might be related to high inhibitory potency. In this paper, we review the anti-inflammatory properties of 6-MSITC and discuss potential molecular mechanisms focusing on inflammatory responses by macrophages.
The peptide glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal L cells in response to food intake. GLP-1 has been proposed as the basis of emerging therapy for patients with type 2 diabetes. However, the effects of GLP-1 on vascular injury in diabetes have not been identified. Advanced glycation end products (AGEs) induce endothelial cell apoptosis and have been implicated in the process of vascular complications from diabetes.
The aim of this work was to investigate whether and how GLP-1 protects endothelial cells from apoptosis induced by AGEs. Human umbilical vein endothelial cells (HUVECs) were treated with AGEs (200 µg/mL) for 48 h in the presence or absence of GLP-1. Cell morphology, viability, apoptosis, ratio of Bcl-2 protein to Bax protein, cytochrome c release, and activity of caspase-9 and -3 were determined.
Treatment of cells with AGEs led to cell morphology changes and decreased cell viability, resulting in apoptosis. GLP-1 alone increased cell viability in a concentration-dependent manner. GLP-1 partially inhibited AGEs-induced apoptosis in HUVECs. GLP-1 increased Bcl-2/Bax ratio, reduced cytochrome c levels in the cytoplasm, and reduced the activity of caspase-9 and -3 in AGEs-treated HUVECs.
AGEs induces apoptosis via the mitochondrion-cytochrome c-caspase protease pathway, and GLP-1 protects endothelial cells by interfering with this mechanism. GLP-1 may represent an anti-apoptotic agent in the treatment of vascular complications arising from diabetes.
In recent years, there has been a great deal of attention toward the field of free radical chemistry. Free radicals reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body's ability to regulate them, a condition known as oxidative stress ensues. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Hence application of external source of antioxidants can assist in coping this oxidative stress. Synthetic antioxidants such as butylated hydroxytoluene and butylated hydroxyanisole have recently been reported to be dangerous for human health. Thus, the search for effective, nontoxic natural compounds with antioxidative activity has been intensified in recent years. The present review provides a brief overview on oxidative stress mediated cellular damages and role of dietary antioxidants as functional foods in the management of human diseases.
While several tools are already available for the separate measurement of the oxidant and antioxidant pools, a single, quick and easy method for determining total oxidative stress would be advantageous. In the present study, we compare the plasma of untreated patients with leukemia/solid gynecological tumors (n = 50) and current regular smokers (n = 50) with a smoking history of >or=10 cigarettes per day to the plasma of healthy blood donors. Standard tools were used to measure total oxidant status, ceruloplasmin activity, total antioxidant capacity, uric acid content and oxidative stress index. Oxidative stress was also evaluated using the controversial d-ROMs test, a commercial method of reactive oxygen species detection. Statistically significant differences between the smokers and the control group were detected for all of the biochemical parameters. Conversely, the differences in the cancer patients were not statistically significant for oxidative stress.
The effects of Wasabia japonica (WJ) were investigated in vitro and in vivo for their anti-oxidant and anti-hypercholesterolemic activities. It was found that the aqueous extracts of WJ leaves (WJL) had strong scavenging activities towards 1,1-Diphenyl-2-picryhydrazyl (DPPH) and nitric oxide (NO) free radicals in cell free systems. WJL also inhibited NO production and the expressions of inducible NO synthase (iNOS) mRNA and enzyme protein, determined by Griess reactions, RT-PCR or Western blotting respectively in Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages cells. The anti-hypercholesterolemic effects of WJ diet were investigated in hypercholesterolemia rats. Sprague-Dawley rats were divided into four groups and were fed with either normal diet (Group 1), or diet containing 1%(w/w) cholesterol (Groups 2, 3 and 4). After 4 weeks, Group 2 was changed to normal diet, Groups 3 and 4 were changed to the diet containing 5% WJ leaf and or 5% WJ root, respectively. 3 weeks after WJ diets, Serum HDL-cholesterol levels were significantly increased in WJ diet groups compared with the normal diet hypercholesterolemia rats. In contrast, the serum LDL-cholesterol levels and liver xanthine oxidase (XO) activity in WJ diet groups were significantly decreased. The results indicate that the WJ extracts have significant anti-oxidant activities, and the WJ diet exhibited anti-hypercholesterolemic action in high cholesterol diet rats, which was companied with modulations of cholesterol metabolism and decrease in liver XO activity.
Wasabi leaf has been reported to show human health benefits without assessment of its safety. This study aims to investigate the mutagenicity, acute and sub-acute toxicity and human trial safety of wasabi leaf extract (WLE). The Ames test was used to assess mutagenicity, while acute and sub-acute toxicity were assessed by oral administration in five-week-old Slc:ICR mice (SPF) and five-week-old Sprague-Dawley (SD) rats, respectively. Human trial safety was further determined in a clinical trial. Twelve healthy subjects, aged 20–64 years and mildly obese (BMI 23.0 to 30.0 kg/m²), were enrolled in the clinical trial, and participants ingested 200 mg WLE daily for 12 weeks. The effect of WLE on fat metabolism was evaluated by visceral fat area (VFA), subcutaneous fat area (SFA), VFA/SFA(V/S) area ratio, body weight, BMI, TG, T-Cho, HDL-C, LDL-C, waist circumference, and body fat percentage. In the Ames test, WLE did not show mutagenicity in the range of 1.2–5000 µg/plate. No acute toxicity was observed in Slc:ICR mice (SPF) administered 5000 mg/kg/day WLE, and no sub-acute toxicity was observed in Crl:CD (SD) rats administered 2500 mg/kg/day WLE. In the human clinical trial, there were no significant differences between the WLE and placebo groups for any outcome measure assessed. Thus, ingestion of 200 mg/day of WLE was demonstrated for the first time to be safe. Taken together, our data on the mutagenicity, acute and sub-acute toxicity and human trial safety of WLE provide the first standard references for wasabi leaf supplement application.
Wasabi (Wasabia japonica Matsumura) is a perennial plant, and its rhizome is widely used as a pungent spice. Wasabi rhizome has been reported to have various physiological activities, but the flower has not been studied in depth. The aim of the present study was to isolate compounds from wasabi flowers and clarify their antioxidant and anti-inflammatory activities. Three phenylpropanoids, one alkaloid and seven flavonoids were isolated from wasabi flowers. Among them, 2″-O-trans sinapoyl isovitexin was identified as a novel compound. Five compounds inhibited 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, with IC50 values of less than 100 µM. Luteolin isolated in this study was found to inhibit nitric oxide production in macrophage-like J774.1 cells, with an IC50 value of 24.1 ± 4.4 µM. Our results indicate that the phenolic compounds in wasabi flowers are effective ingredients for antioxidant and anti-inflammatory activities. For these reasons, wasabi flowers are expected to be used effectively as a functional food.
Objective
Although dissolving microneedle patches have been widely studied in the cosmetics field, no comparisons have been drawn with the topical applications available for routine use. In this study, two wrinkle‐improving products, adenosine‐loaded dissolving microneedle patches and an adenosine cream, were evaluated for efficacy, with respect to skin wrinkling, dermal density, elasticity, and hydration, and safety in a clinical test on the crow's feet area.
Methods
Clinical efficacy and safety tests were performed for 10 weeks on 22 female subjects with wrinkles around their eyes. The adenosine‐loaded dissolving microneedle patch was applied once every 3 days, in the evening, for 8 weeks to the designated crow's feet area. The adenosine cream was applied two times per day, in the morning and evening, for 8 weeks to the other crow's feet area. Skin wrinkling, dermal density, elasticity, and hydration were measured by using PRIMOS® premium, Dermascan® C, Cutometer® MPA580, and Corneometer® CM 825, respectively. In addition, subjective skin irritation was evaluated by self‐observation, and objective skin irritation was assessed through expert interviews.
Results
The adenosine‐loaded dissolving microneedle patches had a similar or better efficacy than the adenosine cream. Both groups showed statistically significant efficacy for almost all parameters (P < 0.05). The dissolving microneedle patches had a long‐lasting effect on the average wrinkle depth (P < 0.05), only showed efficacy in dermal density (P < 0.05), had an early improving effect on elasticity (P < 0.05), and demonstrated better hydration efficacy (P < 0.001). No adverse effects were observed in either group during the test period.
Conclusions
In the clinical efficacy test of four skin‐improvement parameters, adenosine‐loaded dissolving microneedle patches showed the same or better effect than the adenosine cream, although the weekly adenosine dose was 140 times lower. The dissolving microneedle patches caused no adverse reactions. These adenosine‐loaded dissolving microneedle patches are expected to be safe, effective, and novel cosmetics for skin improvement.
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Melanoma is the deadliest form of skin cancer and its incidence is rising, creating a costly and significant clinical problem. Exposure to ultraviolet (UV) radiation, namely UVA (315-400 nm) and UVB (280-315 nm), is a major risk factor for melanoma development. Cumulative UV radiation exposure from sunlight or tanning beds contributes to UV-induced DNA damage, oxidative stress, and inflammation in the skin. A number of factors, including hair color, skin type, genetic background, location, and history of tanning, determine the skin's response to UV radiation. In melanocytes, dysregulation of this UV radiation response can lead to melanoma. Given the complex origins of melanoma, it is difficult to develop curative therapies and universally effective preventative strategies. Here, we describe and discuss the mechanisms of UV-induced skin damage responsible for inducing melanomagenesis, and explore options for therapeutic and preventative interventions. This article is protected by copyright. All rights reserved.
The finding of hydrogen peroxide (947 nmol/100 g) in the paste of wasabi (Wasabia japonica Matsum) stems led us to restrain oxidation of 6-methylthiohexyl isothiocyanate by eliminating hydrogen peroxide. The effects of addition of catalase or peroxidase and sodium ascorbate were examined. When we added catalase or peroxidase and sodium ascorbate, this substance remained a twice and quadruple amount, respectively. Some enzymatic inhibitors were tested for inhibiting 6-methylthiohexyl isothiocyanate oxidation. When EDTA was added, about twice as much 6-methylthiohexyl isothiocyanate as that in the control remained. In the addition of EGCG, 6-methylthiohexyl isothiocyanate was not reduced. But the addition of EDTA or EGCG had no effect on the stabilization of allyl isothiocyanate.
Tyrosinase is a key enzyme that catalyzes melanogenesis in human skin. It oxidizes tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) and subsequently to dopachrome, which further polymerizes to melanin pigments. Therefore finding an effective tyrosinase inhibitor, either from synthetic or natural sources, is not only useful as skin whitening agents in cosmetic application, but also beneficial in treating melanin-related disorders. The present study reports of the optimized and validated results of a cell-based tyrosinase assay using B16F10 murine melanoma cell line, which produces melanin pigments and has been used extensively in antimelanogenesis studies. The optimization studies involved 3 parameters (1) optimal seeding cell number per well for total protein extraction; (2) optimal dopachrome formation from enzymatic reaction between total protein (tyrosinase source) and L-DOPA (substrate); and (3) optimal incubation period after the addition of substrate. The present study demonstrates that using seeding cell number of 2 × 105 cells/well, total protein of 40 μg, L-Dopa of 5 mM,and at an incubation period of 1 hour at 37°C provided the optimal response on cultured melanoma cells. Kojic acid, a standard tyrosinase inhibitor, was used as a positive control in the optimized cell-based tyrosinase assay to validate the usefulness of the assay. CONCLUSION: The use of the mentioned protocol is sensitive to determine changes in melanoma cells as the result of tyrosine inhibitors.
The methanol extracts of wasabi leaves (Wasabia japonica Matsumura) from Shizuoka, Japan have been found to inhibit the production of nitric oxide (NO) in an in vitro assay using murine macrophage J774.1 cells stimulated with lipopolysaccharide. Fourteen known compounds, including five phenylpropanoid glycosides (1 -4 and 9), three phenylpropanoids (5 -7), a phenolic glycoside (8), two flavonoid glycosides (10 and 11), two terpenoids (12 and 13) and a carotenoid (14), were isolated from wasabi leaves collected from Shizuoka and their structures elucidated using spectroscopic methods. This study therefore represents the first reported isolation of compounds 8, 9, 12, 13 and 14 from wasabi leaves. 5-Hydroxy ferulic acid methyl ester (5) and all-trans-lutein (14) were found to inhibit NO production in J774.1 cells with IC50 values of 22 and 25 μM, respectively. The results therefore suggested that these compounds are the active components of wasabi leaves.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Increased oxidative stress has been shown to be a prominent and early feature in AD. Medicinal plants with antioxidant activities have been used traditionally in the treatment of several human diseases. The present study aims to investigate the effect of Salvia triloba and Piper nigrum plant extracts on the oxidative stress status in Alzheimer's disease induced in rats.
70 male rats were enrolled in this study and were classified into 7 groups (ten each). Group 1: control group, group 2: AD-induced rats by aluminum chloride, and served as positive control; group 3: AD group treated with Rivastigmine in a dose of 0.3 mg/kg b. wt. daily for three months; group 4 & 5: AD group treated with total extract of Salvia triloba in a dose of 750 or 375 mg/kg b. wt. respectively, daily for three months; group 6 & 7: AD group treated with total extract Piper nigrum in a dose of 187.5 or 93.75 mg/kg b. wt. respectively, daily for three months. After three months of treatment animals' sera and brain samples were collected. Malondialdehyde (MDA), nitric oxide (NO) and total antioxidant capacity (TAC) were determined in serum while superoxide dismutase (SOD) in erythrocyte. Brain samples were divided sagitally into two portions, the first portion was separated for determination of acetylcholine (Ach) and acetycholinesterase (AchE). The second portion was used for histopathological investigation.
The results indicated that extracts of Salvia triloba and Piper nigrum as well as Rivastigmine showed significant increase in brain Ach, serum TAC and SOD and significant decreases in brain AchE, MDA and NO in AD-induced rats. Moreover, histological investigation of brain sections showing nearly normal histological structure of hippocampus. Treatment with Salvia triloba in a dose of 750 mg/kg b. wt. was more powerful in protection from Alzheimer's disease than Piper nigrum, as indicated by both biochemical and histopathological findings.
This study revealed that the treatment of AD-induced rats with Salvia triloba and Piper nigrum, total plant extracts significantly reduced the oxidative stress status and ameliorates the neurodegeneration characteristic of Alzheimer's diseases in rats. Noteworthy, Salvia triloba extract showed more interest in improvement Alzheimer's disease in rats.
Accumulation of degenerated elastic fibers in the sun-exposed skin designated as actinic elastosis is a histological hallmark of photodamaged skin. Previous studies have indicated that the elastic fibers of actinic elastosis interact with lysozyme and are modified by N(ɛ)-(carboxymethyl)lysine (CML), one of the major advanced glycation end products (AGEs). We studied here how CML modification of elastin is involved in the pathogenesis of actinic elastosis. The CML-modified insoluble elastin became resistant to neutrophil elastase digestion, which was reversed by treatment with aminoguanidine, a potent inhibitor of AGE formation. In a temperature-dependent aggregation assay, CML-modified elastin rapidly formed self-aggregates, the size of which was larger than unmodified elastin. The elastic fiber sheets prepared from CML-modified α-elastin showed 3D wider diameter, tortuous appearance, and decreased elasticity on tensile tests. The CML-modified α-elastin, but not unmodified α-elastin, was found to bind to lysozyme in vitro, supporting the immunohistochemical findings that the antibodies for lysozyme and CML reacted simultaneously with the elastic fibers of actinic elastosis and UV-irradiated skin. The glycated elastin is likely to cause the accumulation of abnormally aggregated elastic fibers and unusual interaction with lysozyme in actinic elastosis.
Advanced glycation end products (AGEs) evoke oxidative stress generation and inflammatory reactions, thus being involved in vascular complications in diabetes. Since oxidative stress and inflammation impair insulin actions as well, it is conceivable that AGEs may play some role in insulin resistance. However, there is no clinical study to examine the relationship between serum levels of AGEs and insulin resistance. This study investigated whether serum AGE levels were independent correlates of insulin resistance in humans.
Three hundred twenty-two nondiabetic Japanese subjects (216 male and 106 female; mean age 61.5 ± 9.1 years) underwent a complete history and physical examination, determinations of blood chemistries, anthropometric and metabolic variables, including AGEs. Serum AGE levels were examined with an enzyme-linked immunosorbent assay.
Mean serum AGE levels were 8.96 ± 2.57 U/mL. In univariate analysis, waist circumference, diastolic blood pressure (BP), mean BP, AGEs, low-density lipoprotein (LDL) cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol (inversely), hemoglobin A1c (GHb), creatinine clearance, uric acid, and high sensitivity C-reactive protein were significantly associated with insulin resistance evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) index. After performing multiple regression analysis, waist circumference (P < 0.001), GHb (P < 0.001), triglycerides (P < 0.001), and AGEs (P < 0.01) still remained significant independently. When age-adjusted HOMA-IR levels stratified by AGE tertiles were compared using ANCOVA, a significant trend was demonstrated in both males and females.
The present study demonstrated for the first time that serum AGE levels were one of the independent correlates of HOMA-IR index, thus suggesting that AGEs may play some pathological role in insulin resistance in humans.
Infection with Helicobacter pylori (H. pylori) can induce gastric disorders, and though its presence cannot explain disease pathogenesis and does not have associations with other factors, it is well known that H. pylori infection causes stomach inflammation following oxidative stress. We examined the suppressive effects of a leaf extract of Wasabia japonica on H. pylori infection and on stress loading in Mongolian gerbils. Following oral administration of wasabi extract of 50 and 200 mg/kg B.W./d for 10 d, the animals were exposed to restraint stress for 90 and 270 min. As for the results, the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in the stomach and oxidative DNA damage in peripheral erythrocytes at 270 min significantly increased. That elevation was significantly suppressed by the addition of the leaf extract. We concluded that the simultaneous loading of H. pylori infection and physical stress loading might induce oxidative DNA damage additively, while a leaf extract attenuated this DNA damage in the stomach as well as the peripheral erythrocytes.
Wasabi has been used as an important spice in Japanese foods. The wasabi leaves were used as a cosmetic material, but its biological activities have not yet been examined. We investigated the effect of isosaponarin derived from wasabi leaf on collagen synthesis in human fibroblasts. The production of type I collagen in human fibroblasts was increased with treatment of wasabi leaf extract. Isosaponarin isolated from wasabi leaves belonged to the group of flavone glycoside, and was the key compound in collagen synthesis from the wasabi leaf ingredients. Isosaponarin increased the type I collagen production at the mRNA gene level. The treatment of isosaponarin did not influence the production of transforming growth factor-beta (TGF-beta) protein, but increased the production of TGF-beta type II receptor (TbetaR-II) protein and TbetaR-II mRNA. Prolyl 4-hydroxylase (P4H) protein and P4H mRNA were increased by treatment with isosaponarin. Heat shock protein 47 (HSP47) was not increased by treatment with isosaponarin. These results suggested that isosaponarin increased collagen synthesis in human fibroblasts, caused by up-regulated TbetaR-II and P4H production.
Although one clinical sign of aging and/or photoaging is a yellowish discoloration of the facial skin, little is known about the cause of this change. In addition to the increase in the epidermal melanin content, it has been suggested that advanced glycation end products (AGEs), which are known to accumulate in photoaged skin, may affect this discoloration.
The objective of this pilot study was to non-invasively investigate the roles of melanin and AGEs in this yellowish discoloration of the facial skin.
We examined the spectral reflectance at the cheek in 40 healthy Japanese women of various ages (mean age, 38.1 years) using a reflectance spectrophotometer and a spectrofluorimeter. The degree of yellowish tint was evaluated in terms of b(*). The amount of melanin in the skin was evaluated by calculating the melanin index (MI) A(640)-A(670) [A(lambda): log(10) (1/reflectance) at a wavelength of lambda]. The amount of AGEs was roughly evaluated using the AGEs index, which is thought to linearly correlate with the amount of intrinsic fluorescence markers irrespective of the concentration of melanin and is defined as follows: AGEs index=I(5)/SQR (I(1)xI(2)). In this equation, the intensities of reflectance are I(1) at an excitation wavelength of 335 nm, I(2) at an emission wavelength of 390 nm and I(5) at 390 nm under an excitation wavelength of 335 nm.
Both b(*) and the AGEs index were significantly correlated with subject age (r=0.34, P<0.05 and r=0.68, P<0.0001, respectively). Significant correlations were also observed between MI and b(*) (r=0.63, P<0.0001) and between the AGEs index and b(*) (r=0.53, P<0.0005). However, no significant correlations were seen between MI and the AGEs index.
The AGEs index does not appear to be influenced by the amount of melanin and may be utilized as an indicator of the amount of AGEs in the skin. AGEs are likely to play a role in the yellowish discoloration of skin with aging.
Cell culture conditions for the selective growth and serial propagation of normal human melanocytes from epidermal tissue are described. In addition to the presence of 2% fetal bovine serum, the human melanocyte cell culture environment contains the following growth factor supplements: epidermal growth factor (10 ng/ml), triiodothyronine (10(-9) M), hydrocortisone, (5 X 10(-5) M), insulin (10 micrograms/ml), transferrin (10 micrograms/ml), 7S nerve growth factor (100 ng/ml) cholera toxin (10(-10) M), and bovine brain extract (150 micrograms/ml). The ability to establish selectively the human melanocyte in vitro has been attributed to the contrast between human epidermal keratinocytes and melanocytes for attachment to fibronectin, while the growth of the human melanocyte has been attributed to the mitogenic activity of the growth factor-supplemented medium. Human melanocytes can be cultivated for at least 15 cumulative population doublings and are capable of [3H]-Dopa incorporation. The growth factor-supplemented medium contains a neutral extract from bovine brain that is a potent source of a human melanocyte mitogen. The biological activity of melanocyte growth factor is described as a heat and alkaline-labile mitogen with an estimated molecular weight of 30,000 by gel exclusion chromatography and a weakly cationic isoelectric point. The mitogen is capable of stimulating the growth of quiescent populations of human melanocytes in vitro. The ability to isolate and propagate normal human melanocytes in vitro permitted an examination of the expression of fibronectin and tissue plasminogen activator. Human epidermal melanocytes established in culture do not contain either tissue plasminogen activator or fibronectin. In contrast, human melanoma cell lines contain immunologically detectable fibronectin and tissue plasminogen activator. The absence of tissue plasminogen activator and fibronectin in normal human melanocytes also occurs under conditions of co-cultivation with human melanoma cells. These contrasts between normal human melanocytes and human melanoma cells may be relevant to the metastatic capabilities of human melanoma.
Estimation of skin diseases in the community is challenging because we do not easily have access to the nonhealthcare-seeking population. A potential tool is a questionnaire asking for self-reported skin complaints. Such an instrument has not yet been developed.
To validate a simple instrument assessing skin morbidity in the general adult population, to predict clinical skin morbidity from self-reported skin complaints.
A questionnaire was drawn up in Norwegian and validated against clinical signs in two samples of an urban population, 100 healthcare-seeking adults in a dermatological clinic, and 100 nonhealthcare-seeking adults. A total self-reported score was calculated and validated against severity of clinical signs (no sign, trivial, moderate or severe). The inter-rater agreement was assessed in a small study including 16 patients from a dermatological clinic.
The participation rate was 98%. The sensitivity was 61%, the specificity 69% and the positive predictive value 82% when the caseness criterion was any clinical sign of skin disease. The agreement was good between the two observers for clinical skin morbidity, with kappa = 0.67.
This questionnaire is a simple tool to evaluate skin morbidity in an adult population. The use of self-reported complaints to predict clinical morbidity may be of value in quantifying and exploring skin diseases at the population level. Further studies are needed to improve the instrument. It is our intention to demonstrate the potential usefulness of this questionnaire in a forthcoming population survey in Norway.
Human skin is repeatedly exposed to UVR that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, as melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UVR on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention.
Advanced Glycation End Products in the Skin: Molecular Mechanisms
- Chen
Arbutin: Mechanism of its depigmenting action in human melanocyte culture
- Maeda