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一种新型注射制剂(结合低分子量和中/高分子量双重量透明质酸与海藻糖)对人体离体皮肤抗糖化治疗特性的评估

Assessment of the Curative Anti-Glycation Properties of a Novel Injectable Formulation Combining Dual-Weight Hyaluronic Acid (Low- and Mid/High-Molecular Weight) with Trehalose on Human Skin Ex Vivo.

作者信息

Chmielewski Robert, Lebiedowska Agata, Barańska-Rybak Wioletta

机构信息

Prime Clinic, Topiel 12, 00-342 Warsaw, Poland.

Positive Pro-Aging Foundation, Topiel 12, 00-342 Warsaw, Poland.

出版信息

Int J Mol Sci. 2025 May 15;26(10):4747. doi: 10.3390/ijms26104747.

Abstract

Glycation influences skin aging through non-enzymatic reactions between reducing sugars and proteins, forming advanced glycation end-products (AGEs) that accelerate skin deterioration. This study evaluates the curative anti-glycation effects of an injectable formulation combining dual-molecular-weight hyaluronic acid (low and mid/high) with trehalose in methylglyoxal-induced glycation in human skin explants. Thirty-six human skin explants were allocated across five experimental groups in a 12-day study. Glycation was induced using methylglyoxal (500 μM) on days 1 and 4, followed by curative product administration on day 5. CML (Nε-(carboxymethyl)lysine) immunohistochemistry was performed to assess glycation levels in the reticular dermis at days 6, 8, and 12, with quantitative analysis conducted through standardized image analysis. The formulation significantly reduced CML formation by 60% on day 6 compared to untreated controls ( < 0.001). Under methylglyoxal-induced glycation stress the product showed sustained curative effects, with CML reductions of 69% on day 6 ( = 0.008), 68% on day 8 ( = 0.012), and 61% on day 12 ( = 0.033) compared to methylglyoxal treatment alone. Cell viability remained unaffected throughout the study period across all experimental conditions. The tested injectable formulation exhibits significant and sustained curative anti-glycation properties in human skin explants for 12 days, effectively counteracting methylglyoxal-induced glycation damage without affecting cell viability. These findings advance anti-aging skin interventions, offering a novel approach to address glycation-induced skin damage with potential applications in clinical dermatology and aesthetic medicine.

摘要

糖基化通过还原糖与蛋白质之间的非酶促反应影响皮肤老化,形成加速皮肤恶化的晚期糖基化终产物(AGEs)。本研究评估了一种可注射制剂(结合了双分子量透明质酸(低分子量和中/高分子量)与海藻糖)对甲基乙二醛诱导的人皮肤外植体糖基化的治疗性抗糖基化作用。在一项为期12天的研究中,将36个人皮肤外植体分配到五个实验组。在第1天和第4天使用甲基乙二醛(500 μM)诱导糖基化,然后在第5天给予治疗产品。在第6天、第8天和第12天进行CML(Nε-(羧甲基)赖氨酸)免疫组织化学,以评估网状真皮中的糖基化水平,并通过标准化图像分析进行定量分析。与未处理的对照组相比,该制剂在第6天显著降低了60%的CML形成(<0.001)。在甲基乙二醛诱导的糖基化应激下,该产品显示出持续的治疗效果,与单独使用甲基乙二醛治疗相比,第6天CML降低69%(=0.008),第8天降低68%(=0.012),第12天降低61%(=0.033)。在所有实验条件下,整个研究期间细胞活力均未受影响。所测试的可注射制剂在人皮肤外植体中表现出显著且持续12天的治疗性抗糖基化特性,有效对抗甲基乙二醛诱导的糖基化损伤,且不影响细胞活力。这些发现推动了抗老化皮肤干预措施的发展,为解决糖基化诱导的皮肤损伤提供了一种新方法,在临床皮肤科和美容医学中具有潜在应用价值。

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