School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
Biomed Pharmacother. 2024 Nov;180:117522. doi: 10.1016/j.biopha.2024.117522. Epub 2024 Oct 10.
The potential therapeutic effects of carnosic acid (CA) on postinflammatory hyperpigmentation (PIH) were evaluated, including its effects on melanin deposition in zebrafish, melanogenesis and melanosome transfer in skin cells and skin wound healing in mice. Our results demonstrated that CA dose-dependently decreased melanin deposition in the skin of juvenile zebrafishes. It also inhibited melanogenesis in melanoma cells and melanosome transfer to keratinocytes. Next, CA was loaded in a liposome-hydrogel system (LP-GEL) to treat skin wounds in mice. The results showed that CA-LP-GEL, as well as LP-GEL, could accelerate skin wound healing and repair the structure of healing skins in mice. Comparatively, the levels of inflammatory factors (IL-1β and TNF-a) in healing skins were significantly increased by LP-GEL, but reduced by CA-LP-GEL. In addition, Fontana-Masson staining analysis of healing skin showed that the melanoma cells were restored by the treatment of LP-GEL and CA-LP-GEL, while the melanin content was significantly increased only by LP-GEL. Real-time PCR data showed that CA decreased the gene expression related with melanogenesis (MITF, TYR and TRP-1), melanosome transfer (MLPH, Myova and Rab27a) and inflammatory cytokines (IL-1β and TNF-α) in vitro and in vivo. In conclusion, CA could reduce melanin deposition in the skin by inhibiting melanogenesis and melanosome transfer. CA-LP-GEL was found to accelerate skin wound healing and suppress inflammation and hyperpigmentation in mice. These results suggest that CA has a big developing potentiality for PIH treatment.
评估了没食子酸（CA）对炎症后色素沉着（PIH）的潜在治疗作用，包括其对斑马鱼皮肤中黑色素沉积、皮肤细胞中黑色素生成和黑素小体转移以及小鼠皮肤伤口愈合的影响。我们的结果表明，CA 呈剂量依赖性地减少了幼年斑马鱼皮肤中的黑色素沉积。它还抑制了黑色素瘤细胞中的黑色素生成和黑素小体向角质形成细胞的转移。接下来，CA 被装载在脂质体-水凝胶系统（LP-GEL）中以治疗小鼠皮肤伤口。结果表明，CA-LP-GEL 以及 LP-GEL 均可加速皮肤伤口愈合并修复小鼠皮肤的愈合结构。相比之下，LP-GEL 可显著增加愈合皮肤中炎症因子（IL-1β和 TNF-α）的水平，但 CA-LP-GEL 可降低其水平。此外，愈合皮肤的 Fontana-Masson 染色分析表明，LP-GEL 和 CA-LP-GEL 处理可恢复黑色素瘤细胞，而仅 LP-GEL 可显著增加黑色素含量。实时 PCR 数据表明，CA 降低了与黑色素生成（MITF、TYR 和 TRP-1）、黑素小体转移（MLPH、Myova 和 Rab27a）和炎症细胞因子（IL-1β和 TNF-α）相关的基因表达，无论是在体外还是体内。总之，CA 可通过抑制黑色素生成和黑素小体转移来减少皮肤中的黑色素沉积。CA-LP-GEL 被发现可加速皮肤伤口愈合并抑制小鼠的炎症和色素沉着过度。这些结果表明 CA 在治疗 PIH 方面具有很大的发展潜力。
