Content uploaded by Fumihito Sugihara
Author content
All content in this area was uploaded by Fumihito Sugihara on Jan 13, 2020
Content may be subject to copyright.
Clinical effects of ingesting collagen hydrolysate on facial skin properties: -A randomized, placebo-controlled, double-blind trial-
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.
... The corneometer is widely used in evaluating the effectiveness of topical products and assessing overall skin health by providing valuable insights into the skin's moisture barrier. Therefore, it is considered as a valuable tool in measuring the skin hydration levels and assessing the efficacy of skincare products [18,[26][27][28][29][30][31][32][33]. On the other hand, the measurement of skin elasticity is often conducted using cutometry, a non-invasive technique that provides valuable insights into skin health. ...
... The results of the subgroup analyses are presented in Figure 10. Figure 6. Forest plot for the subgroup analysis of skin hydration expressed as long-term (>8 weeks) and short-term (<8 weeks) in patients supplemented with HC and patients in the placebo group [26][27][28][30][31][32][33][34][35]39,40,43,44,[46][47][48][49][50]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity). ...
... (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity). [26,28,29,31,[33][34][35]37,39,41,43,48,49]. ...
This paper presents a systematic review and meta-analysis of 26 randomized controlled trials (RCTs) involving 1721 patients to assess the effects of hydrolyzed collagen (HC) supplementation on skin hydration and elasticity. The results showed that HC supplementation significantly improved skin hydration (test for overall effect: Z = 4.94, p < 0.00001) and elasticity (test for overall effect: Z = 4.49, p < 0.00001) compared to the placebo group. Subgroup analyses demonstrated that the effects of HC supplementation on skin hydration varied based on the source of collagen and the duration of supplementation. However, there were no significant differences in the effects of different sources (p = 0.21) of collagen or corresponding measurements (p = 0.06) on skin elasticity. The study also identified several biases in the included RCTs. Overall, the findings suggest that HC supplementation can have positive effects on skin health, but further large-scale randomized control trials are necessary to confirm these findings.
... In a study by Proksch et al. [35], consuming 2.5 g of HC daily for 8 weeks enhanced the production of the dermal ECM constituents, including elastin and procollagen type I, leading to a decrease in wrinkles' severity around the eyes. Using similar interventions, Sugihara et al. [36] observed significant improvements in skin roughness, elasticity and hydration, while on the contrary, Proksch et al. [37] did not confirm any significant impact of even a double (5g) HC dose on skin roughness, hydration, or trans-epidermal water loss (TEWL, measure for skin barrier function). In a study conducted by Choi et al. [38] and Koizumi et al. [39], a 12-week supplementation with 3 g of HC enhanced skin elasticity and hydration. ...
... .3% (to 35.16 (95% CI 33.[35][36].97), p < 0.001) increase on average at 16-week follow-up, both significant in comparison to placebo. The observed results for the CPHA group were similar, with the intervention effect reaching an 11.3% significant increase on average (to 33.20 (95% CI 31.65-34.74); ...
Collagen dietary supplements are becoming increasingly popular as a means to reduce signs of skin ageing. The objective of this three-way, randomised, placebo-controlled, double-blind study was to examine and contrast the effects of dietary supplementation with a daily dose of 5 g hydrolysed collagen with 80 mg of vitamin C (CP product) and their combination with 30 mg of hyaluronic acid (CPHA product) over 16 weeks. Validated methods were utilised for the objective evaluation of skin parameters. In total, 87 subjects (women, 40–65 years) completed the entire trial, distributed across the groups as follows: placebo group (n = 29), CPHA group (n = 28), and CP group (n = 30). The results showed beneficial effects of both test products, with notable enhancements in dermis density, skin texture, and a reduction in the severity of wrinkles. In contrast, the administration of either of the products did not yield any significant impacts on skin elasticity or hydration. Observation of the investigated skin parameters did not show superior effects of the addition of hyaluronic acid (HA) to collagen. Therefore, the ability of supplementation with HA to improve the effects on investigated skin parameters beyond the supplementation of collagen alone cannot be confirmed.
... Collagen, the most common type of protein found in skin as well as tendons and bones, assists fibroblasts forming in the dermis, promoting the growth of new cells and replacing dead skin cells. Oral supplement of collagen has been linked to improved firmness, suppleness, moisture, smoothness, and elasticity of skin [91][92][93] , although larger-scale study is needed to determine whether commercially available products are useful for long-term use. Used topically, certain mixtures of amino acids, such as arginine and ornithine, have been proven to promote the disposition of collagen in wounds [94][95][96] . ...
Computational molecular design -- the endeavor to design molecules, with various missions, aided by machine learning and molecular dynamics approaches, has been widely applied to create valuable new molecular entities, from small molecule therapeutics to protein biologics. In the small data regime, physics-based approaches model the interaction between the molecule being designed and proteins of key physiological functions, providing structural insights into the mechanism. When abundant data has been collected, a quantitative structure-activity relationship (QSAR) can be more directly constructed from experimental data, from which machine learning can distill key insights to guide the design of the next round of experiment design. Machine learning methodologies can also facilitate physical modeling, from improving the accuracy of force fields and extending them to unseen chemical spaces, to more directly enhancing the sampling on the conformational spaces. We argue that these techniques are mature enough to be applied to not just extend the longevity of life, but the beauty it manifests. In this perspective, we review the current frontiers in the research \& development of skin care products, as well as the statistical and physical toolbox applicable to addressing the challenges in this industry. Feasible interdisciplinary research projects are proposed to harness the power of machine learning tools to design innovative, effective, and inexpensive skin care products.
... 2 The peptides could be retained at a high level in the rat skin for up to 14 days post-administration. 3 Previous studies have demonstrated that the oral ingestion of collagen peptides from various sources effectively improves stratum corneum (SC) water content, 4 reduces transepidermal water loss (TEWL), 5 and enhances skin elasticity. 6,7 However, there is still a lack of clinical evidence supporting the effectiveness of collagen peptides from tuna skin in promoting human skin health. ...
Background
Collagen peptides from various sources demonstrate benefits in health and well‐being both in vitro and in clinical trials. However, there is a scarce study of collagen peptides from Tuna on skin health.
Aims
To investigate the impact of collagen peptides derived from Tuna (Katsuwonus pelamis and Thunnus albacares) on skin health, utilizing in vitro biological studies and a randomized controlled trial.
Methods
In vitro biological studies on human dermal primary fibroblasts were evaluated in terms of collagen and elastin synthesis and senescent cell inhibition. A randomized, placebo‐controlled, double‐blind clinical trial was conducted on 72 women who were randomly assigned to receive either tuna collagen peptides (n = 36) or a placebo (n = 36) orally for 8 weeks and 2 weeks post‐ingestion by measuring skin hydration, transepidermal water loss (TEWL), skin elasticity, and skin density.
Results
In vitro biological effects demonstrated dose‐dependent positive results in increasing collagen and elastin synthesis and reducing senescent cells. The effects on collagen and senescent cells plateaued at high concentrations. A clinical trial showed that the test group experienced a significant increase in skin hydration, elasticity, and density, along with a decrease in TEWL compared to the baseline. The test and placebo groups showed statistically significant differences at 8 weeks for all parameters except for the TEWL at the face. All positive effects were substantially retained even after 2 weeks of discontinuation.
Conclusions
These findings demonstrate the significant potential of tuna collagen peptides to promote human skin health, warranting further investigation as a potential nutraceutical.
... Subsequently, they are excreted into the urine (Ichikawa et al. 2010;Iwai et al. 2005;Kawaguchi et al. 2012;. CP have various beneficial effects, such as enhancement of bone strength (König et al. 2018;Wu J et al. 2004), improvement of joint (Benito-Ruiz et al. 2009;Kumar et al. 2015;Kimira et al. 2019) and skin conditions (Inoue et al. 2016;Koizumi et al. 2018;Proksch et al. 2014;Sugihara et al. 2015;Himeno et al. 2022), and reduction of blood lipid levels (Saito et al. 2009;Tometsuka et al. 2021;Woo et al. 2018). In addition, CP can improve fasting blood glucose and HbA1c levels and the homeostasis model assessment ratio (HOMA-R; an important indicator for insulin resistance) in patients with type II diabetes (T2D) (Devasia et al. 2018;Devasia et al. 2020). ...
In this randomized, double-blind, placebo-controlled study, we investigated the effects of collagen peptides (CP) containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine on the advanced glycation end products (AGEs) levels in the skin and subcutaneous blood vessel walls. Thirty-one individuals aged 47–87 years were randomly assigned to receive either 5 g/day fish-derived CP or a placebo for 12 weeks. Body and blood compositions and AGEs levels were measured at the beginning and end of the study. No adverse events were observed, and both groups’ blood and body compositions did not change significantly. However, the CP group had significantly lower AGEs levels and a slightly lower insulin resistance index (HOMA-R) than the placebo group. In addition, the % changes in AGEs and HOMA-R levels were positively and strongly correlated in both groups. These findings suggest that fish-derived CP may be effective in reducing AGEs levels and improving insulin resistance.
... 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). ...
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. ...
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.
Collagen is one of the main components of the extracellular matrix of the dermis and articular cartilage and influences the body’s mechanical, organizational, and tissue formation properties. Produced from food industry by-products, it is considered a nutraceutical product widely used as an ingredient or supplement in food, pharmaceutical, and cosmetic industries. This study aimed to conduct a literature review on the scientific evidence regarding the beneficial effects of collagen consumption in the treatment of skin and orthopedic diseases. Literature data have shown that hydrolyzed collagen supplementation promotes skin changes, such as decreased wrinkle formation; increased skin elasticity; increased hydration; increased collagen content, density, and synthesis, which are factors closely associated with aging-related skin damage. Regarding orthopedic changes, collagen supplementation increases bone strength, density, and mass; improves joint stiffness/mobility, and functionality; and reduces pain. These aspects are associated with bone loss due to aging and damage caused by strenuous physical activity. Thus, this review addresses the economic and health potential of this source of amino acids and bioactive peptides extracted from food industry by-products.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.