Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
UNISKIN Research Institute on Skin Aging, Inertia Shanghai Biotechnology Co., Ltd., Shanghai, China.
J Cosmet Dermatol. 2023 Jul;22(7):2040-2049. doi: 10.1111/jocd.15662. Epub 2023 Feb 10.
BACKGROUND: Aging is responsible for the majority of skin and soft tissue remolding in humans. Retinol and its derivatives or retinoids effectively intervene skin aging process. Nevertheless, retinoids usually induce skin intolerance, especially among the Chinese, and thus, their application to prevent skin aging is yet to be well accepted. The study of optimal composition and concentration of retinoids is necessary to offer strong antiaging efficacies with minimum irritations. Therefore, a better understanding of retinol and its derivatives is acutely needed to develop strategies to combat skin aging. OBJECTIVE: In this study, we aimed to determine the optimal ratio of two retinol derivatives-hydroxypinacolone retinoate (HPR) and retinyl propionate (RP) in terms of dermal remodeling and skin aging prevention-and to investigate their synergistic antiaging effects both in vitro and in vivo. METHODS: An in vitro human foreskin fibroblast (HFF-1) cell model was established to evaluate the cell viability of HPR and/or RP treatment. In addition, the antiaging and retinol receptor genes expressions in HFF-1 cells cotreated with HPR and RP were quantified. The in vivo adverse reaction evaluation of skincare serums containing various levels of retinol or the optimal HPR and RP combination termed Gravi-A was performed by 24 h patch tests in 33 subjects prior to the clinical research. Last but not the least, clinical research with 42 Chinese urban women was conducted to assess the in vivo antiaging efficacy of the skincare serum containing this optimal retinoid combination. RESULTS: The combination of HPR and RP at the weight ratio of 5:9 was shown to achieve the optimal in vitro antiaging performance. Coadministration of 5 μg/mL HPR and 9 μg/mL RP to HFF-1 cells promoted their proliferation at 24 h and synergistically enhanced the expressions of type IV collagen, CRBP-I, and RARB genes. In addition, the skincare serum containing HPR and RP combination at 5:9 weight ratio demonstrated superior in vivo anti-wrinkle and skin elasticity improvement benefits without any adverse reactions, while retinol in the same concentration exerted much higher adverse effect. Skin wrinkles, skin smoothness, TEWL, skin elasticity R2 and R5 were improved by 8.3%, 11.9%, 25.7%, 14.5%, and 22.6%, respectively, after 8-week use. CONCLUSION: Our results indicated the advanced antiaging effect of HPR and RP combination both in vitro and in vivo. In addition, little adverse effect was observed in this study, in comparison with retinol. This combination named as Gravi-A is a potential therapeutic strategy to prevent skin aging, especially for Chinese women.
背景：衰老导致人类皮肤和软组织重塑。视黄醇及其衍生物或类视黄醇可有效干预皮肤衰老过程。然而，类视黄醇通常会引起皮肤不耐受，尤其是在中国人群中，因此，其在预防皮肤衰老方面的应用尚未被广泛接受。需要研究类视黄醇的最佳组成和浓度，以提供最小刺激的强抗衰老功效。因此，迫切需要更好地了解视黄醇及其衍生物，以制定对抗皮肤衰老的策略。
目的：本研究旨在确定两种视黄醇衍生物-羟频哪酮视黄酸酯（HPR）和视黄醇丙酸酯（RP）在皮肤重塑和预防皮肤衰老方面的最佳比例，并在体外和体内研究其协同抗衰老作用。
方法：建立体外人包皮成纤维细胞（HFF-1）细胞模型，以评估 HPR 和/或 RP 处理的细胞活力。此外，还定量检测了 HFF-1 细胞共处理 HPR 和 RP 后抗衰老和视黄醇受体基因的表达。在进行临床研究之前，通过 24 小时斑贴试验，对含有不同水平视黄醇或最佳 HPR 和 RP 组合的护肤品血清（称为 Gravi-A）在 33 名受试者中的皮肤进行了体内不良反应评价。最后但并非最不重要的是，对 42 名中国城市女性进行了临床研究，以评估含有这种最佳类视黄醇组合的护肤品血清的体内抗衰老功效。
结果：HPR 和 RP 的重量比为 5:9 时，显示出最佳的体外抗衰老性能。将 5μg/mL HPR 和 9μg/mL RP 共给药至 HFF-1 细胞可促进其在 24 小时时的增殖，并协同增强 IV 型胶原、CRBP-I 和 RARB 基因的表达。此外，含有 HPR 和 RP 组合（重量比为 5:9）的护肤品血清显示出优越的体内抗皱和皮肤弹性改善效果，没有任何不良反应，而相同浓度的视黄醇则表现出更高的不良反应。使用 8 周后，皮肤皱纹、皮肤光滑度、TEWL、皮肤弹性 R2 和 R5 分别改善了 8.3%、11.9%、25.7%、14.5%和 22.6%。
结论：我们的结果表明，HPR 和 RP 联合应用具有体外和体内的抗衰老作用。此外，与视黄醇相比，本研究观察到的不良反应较小。这种名为 Gravi-A 的组合是预防皮肤衰老的一种有潜力的治疗策略，特别是对中国女性。
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