State Key Laboratory of Component Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Formulation, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
State Key Laboratory of Component Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Formulation, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
J Ethnopharmacol. 2024 Jan 10;318(Pt B):116996. doi: 10.1016/j.jep.2023.116996. Epub 2023 Aug 19.
The skin is affected by endogenous and exogenous factors, which are the intuitive consequence expression of aging. Aging not only affects the aesthetics of the skin but also causes the decline of skin functions, leading to many skin diseases and even skin cancer. Anti-aging formula (AAF) has various biological effects such as antioxidants, regulation of intestinal flora metabolism, anti-aging, and memory improvement. However, it is not clarified whether it could be anti-aging of the skin and the anti-aging mechanism.
This study aimed to investigate whether AAF could prevent skin from oxidative stress-induced senescence and explore the underlying molecular mechanisms.
A mouse skin oxidative stress aging model was established based on ultraviolet (UV) irradiation, and parameters such as skin water content, melanogenesis, wrinkle production, pathological changes, and aging marker proteins were measured to elucidate whether AAF has an anti-aging effect on the skin. Subsequently, transcriptome sequencing (RNA-Seq) was used to identify target genes. An in vitro cellular senescence model was established to assess the role of AAF against cellular oxidative stress senescence by detecting senescence-related markers, while the specific mechanism of action of AAF in delaying skin senescence was elucidated by silencing or overexpression of targets.
In vivo experiments demonstrated that AAF significantly increased skin water content, reduced skin sensitivity and melanin content, slowed wrinkles, improved UV-induced epidermal thickening, increased collagen fiber content, improved elastic fiber morphology, and reduced the expression of senescence proteins P21 and P16 in skin tissues. The RNA-Seq results identified chemokine receptor 2 (CXCR2) as one of the potential targets for delaying skin senescence. In vitro experiments showed that AAF markedly improved the aging phenotype, and knockdown or overexpression experiments verified the essential role of CXCR2 in the skin senescence process. Mechanistic studies suggested that AAF inhibited the P38/P53 pathway by reducing CXCR2 expression, which improved the aging phenotype, reduced oxidative damage, and ultimately delayed cellular senescence.
The results reveal that AAF protects skin from oxidative stress-induced senescence by regulating the expression of critical target CXCR2, reducing P38 protein phosphorylation, and inhibiting P53 pathway activation. These discoveries implicate the potential of AAF in the protection of skin aging disease.
皮肤受到内源性和外源性因素的影响，这些因素是衰老的直观后果表现。衰老不仅会影响皮肤的美观，还会导致皮肤功能下降，引发许多皮肤疾病，甚至皮肤癌。抗衰老配方（AAF）具有抗氧化、调节肠道菌群代谢、抗衰老和改善记忆等多种生物学效应。然而，目前尚不清楚它是否可以抗衰老皮肤以及抗衰老的机制。
本研究旨在探讨 AAF 是否可以预防皮肤氧化应激诱导的衰老，并探索其潜在的分子机制。
基于紫外线（UV）照射建立了小鼠皮肤氧化应激衰老模型，测量皮肤水分含量、黑色素生成、皱纹生成、病理变化和衰老标志物蛋白等参数，以阐明 AAF 是否对皮肤具有抗衰老作用。随后，进行转录组测序（RNA-Seq）以鉴定靶基因。建立体外细胞衰老模型，通过检测衰老相关标志物来评估 AAF 对抗细胞氧化应激衰老的作用，同时通过沉默或过表达靶基因来阐明 AAF 延缓皮肤衰老的具体作用机制。
体内实验表明，AAF 可显著增加皮肤水分含量，降低皮肤敏感性和黑色素含量，减缓皱纹生成，改善 UV 诱导的表皮增厚，增加胶原纤维含量，改善弹性纤维形态，并降低皮肤组织中衰老蛋白 P21 和 P16 的表达。RNA-Seq 结果鉴定出趋化因子受体 2（CXCR2）是延缓皮肤衰老的潜在靶标之一。体外实验表明，AAF 显著改善了衰老表型，并且敲低或过表达实验验证了 CXCR2 在皮肤衰老过程中的重要作用。机制研究表明，AAF 通过降低 CXCR2 表达抑制 P38/P53 通路，改善衰老表型，减少氧化损伤，最终延缓细胞衰老。
研究结果表明，AAF 通过调节关键靶标 CXCR2 的表达，降低 P38 蛋白磷酸化，抑制 P53 通路激活，保护皮肤免受氧化应激诱导的衰老。这些发现暗示了 AAF 在保护皮肤衰老疾病方面的潜力。
