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Clinical effects of ingesting collagen hydrolysate on facial skin properties: -A randomized, placebo-controlled, double-blind trial-

Authors:
  • Nitta Gelatin Inc., Osaka, Japan

Abstract

Objectives: The objective of this research was to investigate the effectiveness of daily ingestion of a specific collagen hydrolysate (CH), which contains prolylhydroxyproline (Pro-Hyp) and hydroxyprolylglycine (Hyp-Gly), on facial skin properties. Methods: In this randomized, placebo-controlled, double-blind trial, 56 women aged 30-55 years were randomized to receive 2.5 g of CH or 5 g of placebo once daily for 8 weeks, with 28 subjects assigned to each group. The hydration, elasticity and roughness properties of facial skin were measured at week 0 (baseline), week 4 and week 8. Results: Levels of skin hydration, elasticity and roughness in subjects who received CH significantly improved between baseline and weeks 4 and 8, while there was no significant improvement in subjects who received placebo. Moreover, the levels of skin elasticity, roughness and the net change of skin hydration improved significantly in the CH group compared to the placebo group by both weeks 4 and 8. Conclusion: The present results suggest that daily ingestion of 2.5 g of CH improves facial skin hydration, elasticity and roughness.
... With regard to food or supplements, the effects of collagen have been controversial, as orally ingested native collagen or its partially hydrolyzed form, gelatin, are not efficiently absorbed [21]. However, several lines of evidence revealed the beneficial role of collagen-derived small peptides, which exhibit high absorbability compared with native collagen [21,22], for a wide variety of tissues including bone [23], joint [24], muscle [25], tendon [26], and skin [27][28][29] in humans. Collagen has been isolated from many marine, brackish water and freshwater sources such as fishes [30][31][32] and mollusks [33][34][35]. ...
... The beneficial effects of collagen peptide for skin conditions have been analyzed by several groups both in rodents [39] and humans [27][28][29]45]. However, to our knowledge, the effects of collagen peptide, ornithine or the combined effects of collagen peptide and ornithine (CPO) on the increase of growth hormone and/or IGF-1 levels, and the subsequent improvements of skin conditions have not been investigated. ...
... The effects of collagen peptide on the improvements of skin moisture, elasticity, wrinkles, ultraviolet-induced erythema and ultraviolet-induced pigmented spots were previously revealed by several groups [28,29,45,[47][48][49]. Furthermore, it has been previously reported that oral administration of marine collagen peptide derived from the skin of Nile Tilapia enhanced the process of wound healing [32]. ...
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Aging-associated changes of skin conditions are a major concern for maintaining quality of life. Therefore, the improvement of skin conditions by dietary supplementation is a topic of public interest. In this study, we hypothesized that a composite supplement containing fish derived-collagen peptide and ornithine (CPO) could improve skin conditions by increasing plasma growth hormone and/or insulin-like growth factor-1 (IGF-1) levels. Twenty-two healthy Japanese participants were enrolled in an 8-week double-blind placebo-controlled pilot study. They were assigned to either a CPO group, who were supplemented with a drink containing CPO, or an identical placebo group. We examined skin conditions including elasticity and transepidermal water loss (TEWL), as well as plasma growth hormone and IGF-1 levels. Skin elasticity and TEWL were significantly improved in the CPO group compared with the placebo group. Furthermore, only the CPO group showed increased plasma IGF-1 levels after 8 weeks of supplementation compared with the baseline. Our results might suggest the novel possibility for the use of CPO to improve skin conditions by increasing plasma IGF-1 levels.
... Functional studies have demonstrated the quick absorption of two bioactive peptides, prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly), in the human plasma, and their retention over a long period following oral ingestion of collagen peptide and their subsequent excretion via the urine (1)(2)(3)(4). Orally ingested collagen peptides exhibit various beneficial effects, such as bone strength enhancement (5,6), joint improvement (7-9), skin condition enhancement (10)(11)(12)(13)(14), and blood lipid-level reduction (15)(16)(17). Fish-derived collagen peptide had been reported to improve fasting blood glucose, hemoglobin A1c, and homeostasis model assessment of insulin resistance levels in Indian patients with type II diabetes (18,19). ...
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Oral ingestion of collagen hydrolysate has various benecial effects. We developed a novel fermented collagen peptide (FCP), different from the conventional collagen peptides, by fermenting gelatin with Aspergillus sojae. This study aimed to investigate the effect of FCP in inhibiting fat accumulation under high-fat loading. Male C57BL/6J mice were fed a low- or high-fat diet, or a high-fat diet including 5% FCP for 28 d. Body weight, visceral fat weight, adiponectin levels, leptin concentration, fatty acid synthase (FAS) activity, and carnitine palmitoyltransferase 1A (CPT) activity were determined. FCP supplementation was found to significantly decrease the body weight, visceral fat weight, leptin concentration, and FAS activity, and increase adiponectin levels and CPT activity compared to that in the high-fat diet-fed group. In conclusion, FCP intake reduced visceral fat weight and body weight in high-fat diet-fed mice.
... Banded fibrils are formed by fibril-forming collagens, which are collagen types I, II, III, V, XI, XXIV, and XXVII. Non-collagenous sequences are found attached to the surface of fibril-producing collagens in the second category of collagens, which includes collagens with collagenous domains interrupted by non-collagenous sequences such as types IX, XII, XIV, and maybe XVI, XIX, XX, XXI, XXII, XXIII, and XXVI [25][26][27][28]. The details of the included articles are shown in a Notably, non-fibrillar collagens include networked, beaded, and anchoring fibrils and invertebrate cuticle collagens. ...
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Resorbable collagen has been utilized to treat wounds, close graft, and tooth extraction sites, and enhance recovery. Collagen-based membranes are also used as barriers in periodontal and implant therapy to limit epithelial migration and allow cells with the regenerative capacity to fill the problem area. This systematic review was carried out to analyze the studies focusing on collagen structure, synthesis, and its applications. A detailed and extensive search was performed with the help of the keywords "collagen structure", "collagen synthesis" and "collagen applications". There was extensive literature search in reliable and authentic databases like PubMed, Scopus, Web of Sciences, Ovidsp, and Cochrane library to obtain papers focusing on collagen structure, synthesis, and applications. During the systematic review, data were obtained concerning the following parameters. Type of study, nature of aim of the study, size of the sample in the study, gender and age of the subjects included in the study, prevalence of skin diseases where collagen was used for treatment, dose of collagen used, form in which collagen was used, the origin of collagen used, analysis of different variables, structure, and synthesis of collagen. Twenty-two studies were included in this systematic review. The studies discussed the structure, synthesis, and applications of collagen in treatment. In studies focusing on the application of collagen supplements, most of the study subjects were females (68.3%). The study subjects included both healthy and unhealthy subjects. The study subjects were divided into two categories. One category was the intervention group, while another group was the placebo group. Collagen was administered in hydrolysate form (90%) in some studies, bovine form (2.3%), and porcine form (3.4%) in other studies. Collagen supplementation was found to provide better results in both healthy and unhealthy effects in improving the health of skin, cornea, bone, periodontium, face, etc. It can be concluded that collagen is an integral part of the body. The application of collagen supplements can be pretty effective in maintaining the proper health of several important structures of the body like skin, face, cornea, nails, periodontium, etc. Thus, a detailed study of the molecular structure of collagen and genes associated with each type of collagen is essential for further research and treatment of collagen-associated disorders.
... For centuries, foods enriched in collagen have been favored by Asian people with the expectancy of an anti-aging effect on skin, with no documented scientific proofs [162]. Only in recent years, a small but growing number of evidences have pointed out the role of MC as enhancer of skin hydration and elasticity, minimizer of wrinkles and repairer of photo-damaged collagen and elastic fibers [61,161,162,[192][193][194][195][196][197][198][199]. Human skin is composed of epidermis, dermis, and subcutaneous tissue [200]. ...
Article
In the last two decades, marine collagen has attracted great scientific and industrial interest as a ‘blue resource’, with potential for use in various health-related sectors, such as food, medicine, pharmaceutics and cosmetics. In particular, the large availability of polluting by-products from the fish processing industry has been the key factor driving the research towards the conversion of these low cost by-products (e.g. fish skin and scales) into collagen-based products with high added value and low environmental impact. After addressing the extraction of collagen from aquatic sources and its physicochemical properties, this review focuses on the use of marine collagen and its derivatives (e.g. gelatin and peptides) in different healthcare sectors. Particular attention is given to the bioactive properties of marine collagen that are being explored in preclinical and clinical studies, and pave the way to an increased demand for this biomaterial in the next future. In this context, in addition to the use of native collagen for the development of tissue engineering or wound healing devices, particularly relevant is the use of gelatin and peptides for the development of dietary supplements and nutraceuticals, specifically directed to weight management and glycemic control. The marine collagen market is also briefly discussed to highlight the opportunities and the most profitable areas of interest.
... Improvement of stratum corneum hydration and/or skin elasticity by collagen peptides has been reported in recent years, and this study supports such findings. [7][8][9][10] The ONS used in this study contained three major amino acids involved in collagen synthesis (proline, glycine, and hydroxyproline) and was abundant in antioxidants (vitamins A, C, and E and zinc). Vitamin C is a potent antioxidant that can neutralize and remove oxidants such as those found in environmental pollutants and after exposure to UV radiation. ...
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Objective: The purpose of this randomized open-label study was to investigate the effect of an oral nutrition supplement containing collagen peptides on stratum corneum hydration and skin elasticity. Methods: The study protocol was registered at the UMIN Clinical Trials Registry (UMIN 000027347). Once-a-day oral administration of a nutrition supplement containing collagen peptides (10.0 g) was instituted in 39 inpatients 65 years or older who were assigned to either the intervention or the control group using a block-randomization design. Stratum corneum hydration and skin elasticity were measured at baseline and at 2, 4, 6, and 8 weeks after the start of the intervention. Results: Mean stratum corneum hydration was significantly increased from 43.7 at baseline to 51.7 at postintervention week 8 in the intervention group (P = .001). Differences in skin elasticity from baseline were significant at postintervention week 6 (P = .026) and week 8 (P = .049). Conclusions: Oral nutrition supplements containing collagen peptides may reduce skin vulnerability in older adults and thus prevent conditions such as skin tears.
... Collagen hydrolysate is prepared from skin, bones, and tendons of animals, or the skin and scales of fish. In human trials with placebo controls, ingestion of collagen hydrolysate (2.5-10 g/day) suppresses transepidermal water loss, reduces wrinkle volume, and increases elasticity of skin [1][2][3][4]. Furthermore, ingestion of collagen hydrolysate moderates the symptoms of osteoarthritis [5,6] and enhances healing of pressure ulcers [7][8][9]. ...
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Prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly) appear in human blood after ingestion of collagen hydrolysate and trigger growth of fibroblasts attached on collagen gel, which has been associated with beneficial effects upon ingestion of collagen hydrolysate, such as improvement of skin and joint conditions. In the present study, inconsistent results were obtained by using different lots of fetal bovine serum (FBS). Fibroblasts proliferated in collagen gel without adding Pro-Hyp and Hyp-Gly and did not respond to addition of Pro-Hyp and Hyp-Gly, which raises doubts about conclusions from prior research. Unexpectedly high levels of hydroxyprolyl peptides, including Pro-Hyp, however, were present in the FBS (approximately 100 µM), and also in other commercially available forms of FBS (70–80 µM). After removal of low molecular weight (LMW, < 6000 Da) compounds from the FBS by size exclusion chromatography, Pro-Hyp and Hyp-Gly again triggered growth of fibroblasts attached on collagen and increased the number of fibroblasts migrated from mouse skin. These results indicate the presence of bioactive hydroxyprolyl peptides in commercially available FBS, which can mask effects of Pro-Hyp and Hyp-Gly supplementation; our work confirms that Pro-Hyp and Hyp-Gly do play crucial roles in proliferation of fibroblasts.
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Background: The dietary supplement industry offers many oral cosmetics that purportedly assist in skin moisturization often with unclear evidence supporting efficacy and safety. To update the accessible proofs pertaining to the safety and effectiveness of oral dietary supplements to facilitate skin moisturizing via an all-around review and meta-analysis. Methods: Three on-line databases [Pubmed, Embase, and Cochrane Library (CENTRAL)] were retrieved from January 2000 to November 2021. An overall 66 randomized controlled trials (RCTs) of skin care were recognized. Meta-analysis was performed for dietary supplements with four or more available research. Results: Oral collagen or ceramide resulted in a statistically significant increase in skin hydration and a decrease in transepidermal water loss (TEWL) compared to placebo. No benefits regarding the improvement of skin conditions in terms of water content and TEWL were observed for lactic acid bacteria or Lactobacillus fermented foods. A statistically significant and positive effect on skin hydration was observed for both hyaluronan and procyanidin, with an unknown effect on TEWL due to insufficient RCTs. There was a non-significant improvement in the water content of stratum corneum for astaxanthin based on subgroup analyses. Among the dietary supplements trialed in ≤ 3 RCTs, the judgment regarding their effects on skin moisturizing was prevented by inconsistent conclusions as well as insufficient research. All food supplements were safe throughout the research (normally ≤ 24 weeks). Conclusion: Oral dietary supplements, including collagen, ceramides, hyaluronan, and procyanidin, were proven to be effective for skin moisturization. At present, for skin moisturization, the proofs supporting the recommendation of other dietary supplements, such as lactic acid bacteria and astaxanthin, are insufficient. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/ identifier CRD42021290818.
Article
Introduction: We aimed to investigate the effect of orally ingested collagen peptides (CPs) on skin condition and elucidate their mechanism of action. Methods: A randomized, placebo-controlled, double-blind trial was conducted in 99 healthy Japanese women, aged 35-50 years. The subjects were randomized into 3 groups (33 subjects/group) to receive 1 or 5 g of CP or placebo once daily for 12 weeks. Skin water content, transepidermal water loss (TEWL), skin elasticity, and skin thickness were evaluated before treatment and after 4, 8, and 12 weeks of treatment. The level of natural moisturizing factor (NMF) constituents in the stratum corneum (SC) was quantified before treatment and after 12 weeks of treatment. Results: Oral ingestion of CP increased the water content in the SC and epidermis and decreased TEWL. Furthermore, the NMF level in the SC was increased. However, skin elasticity and skin thickness remained unchanged. Conclusions: The improvement in skin water content following the oral ingestion of CP can be attributed to an increase in the level of NMF in the SC. Trial registration: UMIN000030375 (retrospectively registered).
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Skin aging has become a recurring concern even for younger people, mainly owing to increased life expectancy. In this context, the use of nutricosmetics as supplements has increased in recent years. Moreover, numerous scientific studies have shown the benefits of hydrolyzed collagen supplementation in improving the signs of skin aging. The objective of this study was to summarize the evidence on the effects of hydrolyzed collagen supplementation on human skin through a systematic review followed by a meta‐analysis of clinical trials focusing on the process of skin aging. A literature search was conducted in the Medline, Embase, Cochrane, LILACS (Latin American and Caribbean Health Sciences Literature), and Journal of Negative Results in BioMedicine databases. Eligible studies were randomized, double‐blind, and controlled trials that evaluated oral supplementation with hydrolyzed collagen as an intervention and reported at least one of the following outcomes: skin wrinkles, hydration, elasticity, and firmness. After retrieving articles from the databases, 19 studies were selected, with a total of 1,125 participants aged between 20 and 70 years (95% women). In the meta‐analysis, a grouped analysis of studies showed favorable results of hydrolyzed collagen supplementation compared with placebo in terms of skin hydration, elasticity, and wrinkles. The findings of improved hydration and elasticity were also confirmed in the subgroup meta‐analysis. Based on results, ingestion of hydrolyzed collagen for 90 days is effective in reducing skin aging, as it reduces wrinkles and improves skin elasticity and hydration.
Article
Background Over the last decade, many researchers tried to evaluate the effects of collagen supplements on skin aging and surprisingly revealed that the interventions improved skin aging parameters without any inconsistency. Aim This systematic review assesses the literature regarding the effects of collagen supplements on skin health parameters in healthy and patient subjects, focusing on mechanisms of action. Methods At the first step of search in the databases, 9057 items were obtained. After removal of duplicate items, 6531 publications remained. Further screening by title and/or abstract resulted in removal of 6500 items. Finally, full texts of the 31 remained items were assessed for eligibility and 10 publications were included in this review. Results The evidences obtained from these systematic reviews indicated that oral administration of intact or hydrolyzed collagen improves clinical manifestation of skin health. Almost all of the included studies reported the beneficial effects of collagen supplementation, and no inconsistencies have been seen in this regard between studies. Conclusions In this systematic review, three different mechanisms of action were clarified for the intervention. Direct effects of collagen peptides on fibroblasts, M2‐like macrophages, and oral tolerance‐related mechanisms are the possible mechanisms for the beneficial effects of collagen supplementation.
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Various dietary supplements are claimed to have cutaneous anti-aging properties; however, there are a limited number of research studies supporting these claims. The objective of this research was to study the effectiveness of collagen hydrolysate (CH) composed of specific collagen peptides on skin biophysical parameters related to cutaneous aging. In this double-blind, placebo-controlled trial, 69 women aged 35-55 years were randomized to receive 2.5 g or 5.0 g of CH or placebo once daily for 8 weeks, with 23 subjects being allocated to each treatment group. Skin elasticity, skin moisture, transepidermal water loss and skin roughness were objectively measured before the first oral product application (t0) and after 4 (t1) and 8 weeks (t2) of regular intake. Skin elasticity (primary interest) was also assessed at follow-up 4 weeks after the last intake of CH (t3, 4-week regression phase). At the end of the study, skin elasticity in both CH dosage groups showed a statistically significant improvement in comparison to placebo. After 4 weeks of follow-up treatment, a statistically significantly higher skin elasticity level was determined in elderly women. With regard to skin moisture and skin evaporation, a positive influence of CH treatment could be observed in a subgroup analysis, but data failed to reach a level of statistical significance. No side effects were noted throughout the study. © 2013 S. Karger AG, Basel.
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Several hydroxyproline (Hyp)-containing food-derived collagen peptides were identified in human blood after oral ingestion of gelatin hydrolysates. However, these types of peptides were not quantified in human plasma. In this report, a sensitive LC-MS/MS method was introduced for simultaneous quantitative analysis of Hyp-containing peptides. All peptide concentrations were determined accurately, with all coefficients of determination (r(2)) >0.999. The method achieved detection and quantification limits of 0.01 pmol/ml and 12.5-1,000 pmol/ml in plasma, respectively. Concentrations were quantified for nine Hyp-containing peptides in human plasma by this method, identifying Pro-Hyp (C(max) = 60.65 +/- 5.74 nmol/ml) as the major constituent of food-derived collagen peptides, while the minor components were Ala-Hyp-Gly, Ser-Hyp-Gly, Ala-Hyp, Phe-Hyp, Leu-Hyp, Ile-Hyp, Gly-Pro-Hyp, and Pro-Hyp-Gly (C(max) from 23.84 to 0.67 nmol/ml). Thus a total of nine Hyp-containing peptides in human plasma were successfully quantified by this approach. The concentration of Hyp-containing peptides is substantially higher than that following oral administration of other peptides.
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Peptides in the blood of subjects before and after collagen hydrolysate ingestion were fractionated by ion exchange and size-exclusion chromatographies and then derivatised with phenyl isothiocyanate. The derivatives were characterised by reserved phase (RP)-HPLC. Prolyl-hydroxyproline (Pro-Hyp), which has been identified in the previous studies, was detected as a major food-derived collagen peptide in the blood of all subjects (n=5). Another major peptide was identified as hydroxyprolyl-glycine (Hyp-Gly) in the blood of four subjects, which has not been detected in previous studies. The ratio of Hyp-Gly to Pro-Hyp depended on subjects and ranged from 0.00 to 5.04. Hyp-Gly was less susceptible to human serum peptidase than Pro-Hyp. Hyp-Gly enhanced the growth of mouse primary fibroblasts on collagen gels in a higher extent than Pro-Hyp. These findings suggest that Hyp-Gly plays a significant role in exerting the biological effects by ingestion of collagen hydrolysate.
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We conducted a placebo-controlled, double-blind 4-week study on the oral intake of either 3 doses of scaled collagen hydrolysate (2.5 g, 5g and 10 g), pig skin collagen hydrolysate (10 g) or placebo in 214 healthy female volunteers (mean age, 34.1 pSD 5.9 years). The volunteers were divided randomly into 5 groups and their skin condition was measured before and after ingestion. The moisture content of the stratum corneum of the cheek showed a significant increase after 4 weeks in all the groups taking the hydrolysates, while it showed a dose-dependent improvement in groups taking collagen hydrolysate (2.5g-10g). A stratified statistical analysis of subjects >30 years old showed significant differences in the groups taking 5g or 10g of hydrolysates (P<0.05), compared with the placebo group. There were no significant differences in transepidermal water loss, viscoelasticity or cutaneous findings between any of the groups. These results indicate that the major change following oral intake of collagen hydrolysate is an improvement in the moisture content of the stratum corneum.
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Prolylhydroxyproline (Pro-Hyp), which is derived from collagen hydrolysate, has been shown to be beneficial for skin and joint health. However, little is known about the distribution of Pro-Hyp in these tissues. In the present study, we investigated the biodistribution of orally administered [(14)C]Pro-Hyp in rats. Whole-body autoradiography at 30 min after administration of [(14)C]Pro-Hyp showed that radioactivity is widely distributed in tissues including skin and articular cartilage, with the highest level of radioactivity observed in the gastric and intestinal walls. Incorporation of radioactivity into cells known to respond to Pro-Hyp such as dermal fibroblasts, synovial cells, chondrocytes, osteoblasts, and osteoclasts was observed. The chemical form of [(14)C]Pro-Hyp-derived radioactivity detected in the tissues was investigated by thin layer chromatography. The radioactive constituents in cartilage extract were two proline-modified peptides (56%), intact Pro-Hyp (5%), and two nonpeptide metabolites (28%). Similar results were obtained for skin and bone marrow. Plasma analysis at 3 to 30 min post-dose suggested that the majority of Pro-Hyp is modified in its proline residue by a first-pass effect without peptide bond hydrolysis. In conclusion, we demonstrated that Pro-Hyp is partly distributed in observed tissues including skin and cartilage in its intact form, which might be responsible for its biological functions.
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Dry skin causes pruritus and discomfort in patients with xerosis and atopic dermatitis. General treatment for skin dryness involves the topical application of an emollient. However, more effective, simpler therapies are desired. Collagen tripeptide (CTP) is a highly purified, non-antigenic, low-allergenic collagen fraction that is known to have various biological effects. To clarify the therapeutic effects of CTP for dry skin using acetone-induced dry skin model mice. ICR mice were treated with acetone followed by oral administration of CTP (80 or 500mg/kg/day) for 3 days. Hyaluronic acid production induced by CTP was assessed using human dermal fibroblasts in vitro and in an acetone-induced dry skin model mice in vivo. Transepidermal water loss (TEWL) and scratching behavior were evaluated. Furthermore, the effects of CTP on intraepidermal nerve fibers and expression of semaphorin 3A (Sema3A) and nerve growth factor (NGF) were examined by immunohistochemistry and quantitative RT-PCR. CTP enhanced hyaluronic acid production in human dermal fibroblasts in vitro and in murine skin in vivo. Oral administration of CTP in acetone-induced dry skin model mice significantly decreased TEWL and suppressed scratching behavior. Intraepidermal nerve growth was dramatically inhibited in CTP-treated mice. Quantitative PCR analysis and immunohistochemical study revealed that CTP abolished the increased NGF and decreased Sema3A levels induced by acetone treatment. Oral administration of CTP improves dry skin and normalizes axon-guidance factors in the epidermis in addition to reducing pruritus. CTP may be used in a new therapeutic strategy against dry skin and pruritus.
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Plasma levels of prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly) in healthy volunteers (n=5) after ingestion of collagen hydrolysate were estimated by liquid chromatography-tandem mass spectrometry. The ratio of Hyp-Gly to Pro-Hyp was distributed in the range of 0.063-0.221. This is a first report for quantification of food-derived Hyp-Gly in human plasma.
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To investigate the long-term effects of marine collagen hydrolysate (MCH) from Chum Salmon skin on the aberrant collagen matrix homeostasis in chronological aged skin, Sprague-Dawley male rats of 4-wk-old were orally administrated with MCH at the diet concentrations of 2.25% and 4.5% for 24 mo. Histological and biochemical analysis revealed that MCH had the potential to inhibit the collagen loss and collagen fragmentation in chronological aged skin. Based on immunohistochemistry and western blot analysis, collagen type I and III protein expression levels in MCH-treated groups significantly increased as compared with the aged control group. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed MCH was able to increase the expressions of procollagen type I and III mRNA (COL1A2 and COL3A1) through activating Smad signaling pathway with up-regulated TGF-βRII (TβRII) expression level. Meanwhile, MCH was shown to inhibit the age-related increased collagen degradation through attenuating MMP-1 expression and increasing tissue inhibitor of metalloproteinases-1 expression in a dose-dependent manner. Moreover, MCH could alleviate the oxidative stress in chronological aged skin, which was revealed from the data of superoxide dismutase activity and the thiobarbituric acid reactive substances level in skin homogenates. Therefore, MCH was demonstrated to have the protective effects on chronological skin aging due to the influence on collagen matrix homeostasis. And the antioxidative property of MCH might play an important role in the process.
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Orally ingested collagen undergoes degradation to small di- or tripeptides, which are detected in circulating blood 2 h after ingestion. The influence of collagen-derived peptides on dermal extracellular matrix components and cell proliferation was studied using cultured human dermal fibroblasts. Of the various collagenous peptides tested here, the dipeptide proline-hydroxyproline (Pro-Hyp) enhanced cell proliferation (1.5-fold) and hyaluronic acid synthesis (3.8-fold) at a dose of 200 nmol/mL. This was concomitant with a 2.3-fold elevation of hyaluronan synthase 2 (HAS2) mRNA levels. Small interfering RNA (siRNA)-mediated knockdown of the HAS2 gene in human dermal fibroblasts inhibited Pro-Hyp-induced HAS2 mRNA transcription and cell mitotic activity. Addition of genistein or H7, a protein kinase inhibitor, abolished the Pro-Hyp-induced HAS2 mRNA stimulation. Pro-Hyp elevated phosphorylation of signal transducer and activator of transcription 3 (STAT3) within a short time period (60 min). These results suggest that Pro-Hyp stimulates both cell mitotic activity and hyaluronic acid synthesis, which is mediated by activation of HAS2 transcription.