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丹皮和川赤芍花提取物通过 cAMP-CREB 相关黑色素生成信号通路抑制小鼠 B16 黑素瘤细胞中的黑色素合成。

Flower extracts from Paeonia decomposita and Paeonia ostii inhibit melanin synthesis via cAMP-CREB-associated melanogenesis signaling pathways in murine B16 melanoma cells.

机构信息

Chongqing Key Lab of Natural Medicine Research, Research Centre of Waste Oil Recovery Technology and Equipment of Chinese Ministry of Education, Chongqing Technology and Business University, Chongqing, China.

College of Communication Engineering, Chongqing University, Chongqing, China.

出版信息

J Food Biochem. 2019 Apr;43(4):e12777. doi: 10.1111/jfbc.12777. Epub 2019 Jan 24.

Abstract

This investigation seeks to identify the effects of the EtOAc fractions of different flower parts of Paeonia decomposita (Pd) and Paeonia ostii (Po) on melanogenesis and their mechanisms of action in B16 melanoma cells. Cell viability assay showed that Pd-1, Po-1 (the petals of Pd or Po), Pd-3 and Po-3 (the stamens of Pd or Po) at 25 μg/ml produced lower toxic activities in B16 cells. Pd-1 and Po-1 extracts considerably reduced the melanin content and inhibited tyrosinase and DOPA oxidase activity. Moreover, Pd-1 and Po-1 down-regulated the expressions of MC1R, MITF, TRP-1, TRP-2, and tyrosinase. These extracts also reduce cAMP levels and inhibited the phosphorylation of CREB, which might be due to the presence of high concentrations of phenolic compounds and flavonoids. Our results suggested that Pd-1 and Po-1 are able to modulate the cAMP-CREB signaling pathway and down-regulate the melanogenesis-related proteins resulting in the observed anti-melanogenic effects. PRACTICAL APPLICATIONS: In China, the flower of Paeonia is often consumed as a dietary supplement and as an additive in skin whitening products. In November 2013, the National Health and Family Planning Commission of the People's Republic of China has approved the flower of Paeonia ostii as a novel food resource. The current study firstly demonstrated that the effects of EtOAc fractions of the petals of Paeonia decomposita (Pd) and Paeonia ostii (Po) considerably reduced the melanin content in B16 cells, which is due to the modulation of the cAMP-CREB signaling pathway followed by the down-regulation of melanogenesis-related proteins. Pd and Po extracts, as natural tyrosinase inhibitors, may serve as good candidates in food additives, cosmetic materials, or even in treating hyperpigmentation diseases.

摘要

本研究旨在探讨芍药属植物牡丹(Pd)和芍药(Po)不同花部分的 EtOAc 部位对黑色素生成的影响及其在 B16 黑素瘤细胞中的作用机制。细胞活力测定表明,Pd-1、Po-1(Pd 或 Po 的花瓣)、Pd-3 和 Po-3(Pd 或 Po 的雄蕊)在 25μg/ml 时对 B16 细胞的毒性活性较低。Pd-1 和 Po-1 提取物显著降低了黑色素含量,并抑制了酪氨酸酶和多巴氧化酶的活性。此外,Pd-1 和 Po-1 下调了 MC1R、MITF、TRP-1、TRP-2 和酪氨酸酶的表达。这些提取物还降低了 cAMP 水平,并抑制了 CREB 的磷酸化,这可能是由于高浓度酚类化合物和类黄酮的存在。我们的结果表明,Pd-1 和 Po-1 能够调节 cAMP-CREB 信号通路,并下调黑色素生成相关蛋白,从而产生观察到的抗黑色素生成作用。实际应用:在中国,芍药的花常作为膳食补充剂和皮肤美白产品的添加剂。2013 年 11 月,中国国家卫生和计划生育委员会批准芍药花作为一种新型食品资源。本研究首次表明,芍药属植物牡丹(Pd)和芍药(Po)花瓣的 EtOAc 部位提取物可显著降低 B16 细胞中的黑色素含量,这是由于 cAMP-CREB 信号通路的调节,随后下调了黑色素生成相关蛋白。Pd 和 Po 提取物作为天然酪氨酸酶抑制剂,可作为食品添加剂、化妆品材料,甚至在治疗色素沉着疾病方面的良好候选物。

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