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一种创新性植物化妆品制剂(费菜和阿拉伯咖啡)对人成纤维细胞自噬的调控及其在一项临床随机安慰剂对照试验中的作用。

Modulation of autophagy by an innovative phytocosmetic preparation (Myrothamnus flabelifolia and Coffea arabica) in human fibroblasts and its effects in a clinical randomized placebo-controlled trial.

机构信息

Research and Development Department, Chemyunion Química Ltda, Sorocaba, Brazil.

Department of Biophysics and Pharmacology, Laboratory of Phytomedicines, Pharmacology, and Biotechnology (PhytoPharmaTech), Institute of Biosciences, São Paulo State University (Unesp), Botucatu, Brazil.

出版信息

J Cosmet Dermatol. 2022 Oct;21(10):4901-4912. doi: 10.1111/jocd.14888. Epub 2022 Mar 12.

DOI:10.1111/jocd.14888
PMID:35220641
Abstract

BACKGROUND

Autophagy is a natural and evolutionary mechanism that reduces cell toxic components and reutilizes metabolites to provide energy and renew cell function, which is linked to a wide range of age-related diseases, including those that affect the skin. Positive modulation of autophagy is useful to treat skin disorders and new active herbal products are potential candidates as autophagy modulators.

AIMS

The present study aimed to evaluate the effects of a phytocosmetic formulation containing Myrothamnus flabellifolia leaf and Coffea arabica seed plant extracts (MflCas) on the ubiquitin-proteasome and autophagy markers in human dermal fibroblasts, and investigate its topical skin effects in a randomized, simple-blind, and placebo-controlled trial.

METHODS

Human dermal fibroblasts were used to determine proteasome activity, protein carbonylation, LC3B protein, and lipofuscin production by luminescence and immune-enzymatic assays, and to determinate gene expression of autophagy biomarkers (Atg5, Atg7, EI24, EIF2A, Park2, foxo1, and mTOR) by RT-PCR. A clinical trial was conducted to evaluate the effects of MflCas on the hand, face, and forearms skin features after treatment by 56 days.

RESULTS

Topical treatment with MflCas improved several skin features of volunteers, mainly skin aging and pigmentation signals. On the hand skin, MflCas 2% after 56 days of treatment, reduced the spots length (30.8%), skin contrast (42.2%), and increased skin homogeneity (63.2%) and skin lightening effect (1.4%). On the face skin, topical treatment after 56 days reduced the spots length (21.5%), wrinkles area (8.1%), and wrinkles volume (5.6%) with an increment in face skin homogeneity (59.5%). These effects were related to the ability of MflCas to reduce proteasome activity protein carbonylation, and lipofuscin level, increase LC3B production, downregulate Atg7 and mTOR genes, and upregulate Park2 gene expressions.

CONCLUSIONS

The phytocosmetic preparation containing Myrothamnus flabellifolia leaf and Coffea arabica seed modulated ubiquitin-proteasome and autophagy process, representing an innovative and safe herbal preparation to improve skin features, mainly acting as skin anti-aging and lightening agent.

摘要

背景

自噬是一种自然和进化的机制,可减少细胞毒性成分并重新利用代谢物提供能量和更新细胞功能,与广泛的与年龄相关的疾病有关,包括影响皮肤的疾病。自噬的正向调节可用于治疗皮肤疾病,新的活性植物产品是作为自噬调节剂的潜在候选药物。

目的

本研究旨在评估含有 Myrothamnus flabellifolia 叶和咖啡种子植物提取物(MflCas)的植物化妆品配方对人真皮成纤维细胞中泛素蛋白酶体和自噬标志物的影响,并在一项随机、简单盲法和安慰剂对照临床试验中研究其局部皮肤作用。

方法

用人真皮成纤维细胞通过发光和免疫酶测定法测定蛋白酶体活性、蛋白质羰基化、LC3B 蛋白和脂褐素的产生,并通过 RT-PCR 测定自噬生物标志物(Atg5、Atg7、EI24、EIF2A、Park2、foxo1 和 mTOR)的基因表达。一项临床试验评估了 MflCas 对面部、手部和前臂皮肤特征的影响,治疗时间为 56 天。

结果

MflCas 的局部治疗改善了志愿者的多项皮肤特征,主要是皮肤老化和色素沉着信号。在手皮肤上,MflCas 2%在 56 天的治疗后,减少了斑点长度(30.8%)、皮肤对比(42.2%),增加了皮肤均匀度(63.2%)和皮肤增白效果(1.4%)。在面部皮肤中,56 天后的局部治疗减少了斑点长度(21.5%)、皱纹面积(8.1%)和皱纹体积(5.6%),同时增加了面部皮肤均匀度(59.5%)。这些效果与 MflCas 降低蛋白酶体活性、蛋白质羰基化和脂褐素水平、增加 LC3B 产生、下调 Atg7 和 mTOR 基因以及上调 Park2 基因表达的能力有关。

结论

含有 Myrothamnus flabellifolia 叶和咖啡种子的植物化妆品制剂调节了泛素蛋白酶体和自噬过程,代表了一种创新和安全的草药制剂,可改善皮肤特征,主要作为皮肤抗衰老和增白剂。

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