背景:作为人体最大的器官,皮肤不断受到紫外线辐射(UVR),导致炎症和变化,反映了时间老化的情况。尽管已经探索了各种小分子药物用于治疗皮肤光老化,它们通常具有低稳定性和高发生率的不良反应。因此,光老化治疗的持续研究,特别是那些使用草药产品的人,仍然是一项关键的临床工作。一种这样的草药产品,Lapagyl,源自拉帕乔树的树皮,具有抗氧化功效,可能有益于对抗皮肤光老化。
目的:本研究旨在评估草药产品Lapagyl对抗UVR诱导的皮肤光老化的功效。此外,它试图揭示Lapagyl促进皮肤细胞外基质再生的机制。
方法:为了研究Lapagyl是否可以缓解皮肤老化和损伤,使用SKH-1无毛小鼠建立UVR辐射模型。评估这些小鼠的背部皮肤的皱纹形成,纹理,水分,经皮水分流失(TEWL),和弹性。进行病理学评估以确定Lapagyl的疗效。此外,采用单细胞测序和光谱分析阐明了Lapagyl在解决UVR诱导的皮肤老化和损伤方面的工作机制和主要成分。
结果:Lapagyl显着减少了UVR引起的皱纹,水分损失,SKH-1小鼠的弹性下降。单细胞测序表明,Lapagyl纠正了UVR引起的细胞比例失衡,UVR诱导的ROS表达降低,保护基底和棘突细胞免受皮肤损伤。此外,Lapagyl通过减少CCL8表达并减少皮肤中UVR诱导的Foxp3调节性T细胞(Tregs)的形成,有效地防止了炎症细胞进入皮肤。病理评估和离体皮肤模型结果均表明Lapagyl有效地减少了UVR诱导的胶原蛋白和弹性蛋白损伤。光谱分析确定红景天苷为Lapagyl治疗后皮肤中残留的主要化合物。一起来看,我们的研究阐明了草药产品Lapagyl在细胞水平上对UVR损伤的皮肤保护机制,揭示了它的免疫调节作用,红景天苷被确定为皮肤的主要活性化合物。
结论:我们的研究全面评估了Lapagyl对皮肤抗紫外线损伤的保护作用,深入研究细胞水平的机制。我们发现Lapagyl通过调节Foxp3+Tregs和CCL途径减轻皮肤炎症和免疫抑制。这些见解表明,Lapagyl具有作为解决皮肤光老化的新型治疗选择的潜力。
BACKGROUND: As the largest organ of the body, the skin is constantly subjected to ultraviolet radiation (UVR), leading to inflammations and changes that mirror those seen in chronological aging. Although various small molecule drugs have been explored for treating skin
photoaging, they typically suffer from low stability and a high incidence of adverse reactions. Consequently, the continued investigation of
photoaging treatments, particularly those utilizing herbal products, remains a critical clinical endeavor. One such herbal product, Lapagyl, is derived from the bark of the lapacho tree and possesses antioxidant efficacies that could be beneficial in combating skin
photoaging.
OBJECTIVE: This research aimed to evaluate the efficacy of the herbal product Lapagyl in combating UVR-induced skin photoaging. Additionally, it sought to unravel the mechanisms by which Lapagyl promotes the regeneration of the skin extracellular matrix.
METHODS: To investigate whether Lapagyl can alleviate skin aging and damage, a UVR radiation model was established using SKH-1 hairless mice. The dorsal skins of these mice were evaluated for wrinkle formation, texture, moisture, transepidermal water loss (TEWL), and elasticity. Pathological assessments were conducted to determine Lapagyl\'s efficacy. Additionally, single-cell sequencing and spectrum analysis were employed to elucidate the working mechanisms and primary components of Lapagyl in addressing UVR-induced skin aging and injury.
RESULTS: Lapagyl markedly reduced UVR-induced wrinkles, moisture loss, and elasticity decrease in SKH-1 mice. Single-cell sequencing demonstrated that Lapagyl corrected the imbalance in cell proportions caused by UVR, decreased UVR-induced ROS expression, and protected basal and spinous cells from skin damage. Additionally, Lapagyl effectively prevented the entry of inflammatory cells into the skin by reducing CCL8 expression and curtailed the UVR-induced formation of Foxp3+ regulatory T cells (Tregs) in the skin. Both pathological assessments and ex vivo skin model results demonstrated that Lapagyl effectively reduced UVR-induced damage to collagen and elastin. Spectrum analysis identified Salidroside as the primary compound remaining in the skin following Lapagyl treatment. Taken together, our
study elucidated the skin protection mechanism of the herbal product Lapagyl against UVR damage at the cellular level, revealing its immunomodulatory effects, with salidroside identified as the primary active compound for skin.
CONCLUSIONS: Our
study provided a thorough evaluation of Lapagyl\'s protective effects on skin against UVR damage, delving into the mechanisms at the cellular level. We discovered that Lapagyl mitigates skin inflammation and immunosuppression by regulating Foxp3+ Tregs and the CCL pathway. These insights indicate that Lapagyl has potential as a novel therapeutic option for addressing skin photoaging.