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生物碱百部胺可增加klotho和核纤层蛋白B1的表达,在体外和体内均能延缓皮肤衰老的发生。

The alkaloid centcyamine increases expression of klotho and lamin B1, slowing the onset of skin ageing in vitro and in vivo.

作者信息

Abadie Sophie, Leduc Claire, Lintner Karl, Bedos Philippe

机构信息

Syntivia, Toulouse, France.

KAL'IDEES, Paris, France.

出版信息

Int J Cosmet Sci. 2021 Oct;43(5):561-572. doi: 10.1111/ics.12731. Epub 2021 Sep 13.

DOI:10.1111/ics.12731
PMID:34403147
Abstract

BACKGROUND

Klotho is a protein known for its beneficial effects on longevity. Centcyamine is an alkaloid present in certain plants whose extracts have an anti-inflammatory effect. Skin fibroblasts are essential to the formation and structure of the dermis.

OBJECTIVE

Centcyamine is an indole-based alkaloid composed of coumaric acid, a resveratrol precursor and methoxytryptamine, which can be both a precursor, or a derivative, of melatonin. Given these building blocks and their well-known bioactivities, it was of interest to explore the potential benefits of using this aryl-alkaloid, in cosmetic skincare applications.

METHODS

We tested cultured normal human dermal fibroblasts (NHDF) in vitro to observe how supplementation with centcyamine improves properties of the cells to counteract the effect of ageing. The expression of genes and proteins of interest was quantified. The effect on doubling time and cell function was evaluated following treatment of the cells over several replication cycles. Skin firmness, red spot index and skin isotropy were measured with Dynaskin , Visia and Primos equipment, respectively, and compared over two months in a vehicle-controlled clinical trial on 60 persons.

RESULTS

Centcyamine activates the expression of the gene KL and the related protein Klotho in dermal fibroblasts. Moreover, centcyamine slows the replicative ageing process of fibroblasts in culture. These cells retain cellular functions identical to those of young cells: the synthesis of lamin B1, a crucial regulatory protein of proliferation, as well as of collagen I and elastin is retained in aged cells. The clinical data are shown to improve skin isotropy in a majority of subjects, to reduce the red spot intensity and to maintain skin firmness in the treated group vs. the vehicle.

CONCLUSION

The alkaloid centcyamine induces changes in the metabolism of the ageing process of human dermal fibroblasts. The up-to-now unobserved implication of both Klotho and lamin B1 to maintain homeostasis of the skin opens new venues for the prevention of age-related changes in skin structure. The in vitro and clinical data, while not demonstrated to be causally related, converge towards a common goal of skin repair and slower ageing processes.

摘要

背景

α-klotho蛋白以其对长寿的有益作用而闻名。百部胺是某些植物中存在的一种生物碱,其提取物具有抗炎作用。皮肤成纤维细胞对真皮的形成和结构至关重要。

目的

百部胺是一种基于吲哚的生物碱,由香豆酸、白藜芦醇前体和甲氧基色胺组成,甲氧基色胺既可以是褪黑素的前体,也可以是其衍生物。鉴于这些组成成分及其众所周知的生物活性,探索在美容护肤应用中使用这种芳基生物碱的潜在益处具有重要意义。

方法

我们在体外测试培养的正常人皮肤成纤维细胞(NHDF),以观察补充百部胺如何改善细胞特性以抵消衰老的影响。对感兴趣的基因和蛋白质表达进行定量。在几个复制周期中对细胞进行处理后,评估对倍增时间和细胞功能的影响。分别使用Dynaskin、Visia和Primos设备测量皮肤紧致度、红斑指数和皮肤各向同性,并在一项针对60人的赋形剂对照临床试验中进行了两个月的比较。

结果

百部胺可激活真皮成纤维细胞中KL基因及相关蛋白α-klotho的表达。此外,百部胺减缓了培养的成纤维细胞的复制性衰老过程。这些细胞保留了与年轻细胞相同的细胞功能:衰老细胞中保留了增殖关键调节蛋白层粘连蛋白B1以及I型胶原蛋白和弹性蛋白的合成。临床数据显示,与赋形剂相比,治疗组中大多数受试者的皮肤各向同性得到改善,红斑强度降低,皮肤紧致度得以维持。

结论

生物碱百部胺可诱导人真皮成纤维细胞衰老过程中的代谢变化。α-klotho和层粘连蛋白B1在维持皮肤稳态方面迄今未被观察到的作用,为预防皮肤结构的年龄相关变化开辟了新途径。体外和临床数据虽然未证明存在因果关系,但都朝着皮肤修复和延缓衰老过程这一共同目标汇聚。

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