Skin Depigmenting Agents in Anti-Aging Cosmetics: A Medicinal Perspective on Emerging Ingredients

Round 1

Reviewer 1 Report

Dear Authors,

thanks for preparing such comparison study of depigmenting ingredients found in your market. As your analysis of data is linked to the use of such ingredients in cosmetic products (anti-aging products) it should be mentioned that such use is regulated by the EU Cosmetic Regulation with its specific annexes. Several substances with depigmentation potential are prohibited in cosmetic products in the EU, others are allowed with strict concentration limits. As safety of such "bio-active" compounds in end-user-products like cosmetics is mandatory, it is proposed to refer to the above-mentioned annexes and the need for a proper safety assessment prior to bring them to the market.

Author Response

We thank reviewer 1 for the comments. We’ve clarified these aspects by adding the following sentence to the manuscript, on lines 68-77: “Cosmetic products are governed by the EU Cosmetics Regulation [Regulation (EC) No. 1223/2009]. This  regulation and corresponding annexes establish the safety requirements for cosmetic products and ingredients, and is regularly updated. Several depigmenting agents are prohibited in cosmetic products in the EU (Annex II) while others are allowed with strict concentration limits (Annex III). As an example, hydroquinone is prohibited in cosmetics products, as it is listed in Annex II of Regulation No 1223/2009. Hence, new compounds aimed to be incorporated as skin depigmenting agents in anti-aging cosmetics should comply to this regulation in order to ensure the safety of the consumers which includes a comprehensive safety assessment.”.

Reviewer 2 Report

This paper summarized the skin depigmenting ingredients included in the anti-aging cosmetic products, their synthetic methodologies, and efficacy comparison. There are several points I want to point out:

1. This paper is more like a review rather than a research paper.
2. In the abstract “While tranexamic acid inhibits melanin 25 synthesis through inhibition of the plasminogen/plasmin system, bakuchiol depigmenting efficacy 26 was attributed to the ability of blocking both α-melanocyte-stimulating hormone and tyrosinase 27 activation and the one of 4-butylresorcinol to the inhibition of both tyrosinase and tyrosinase-related 28 protein-1 (TRP-1).”, the description of latter half part is not clear, please correct.

Author Response

We thank reviewer 2 for the comments and understand his/her concern on the similarity of this manuscript with a review paper. However, this work represents a market study, where all the information available in the studied anti-aging product’s labels was collected and analysed. This analysis focused on the top active ingredients with highest usage frequency among the selected products and the novelties were thorough analysed concerning mechanisms of action and available synthetic methodologies.

The referred sentence was changed to “Regarding their mechanisms of action, tranexamic acid inhibits melanin synthesis through inhibition of the plasminogen/plasmin system. Bakuchiol depigmenting efficacy was attributed to the ability of blocking both α-melanocyte-stimulating hormone and tyrosinase activation, while 4-butylresorcinol exerts its action through the inhibition of both tyrosinase and tyrosinase-related protein-1 (TRP-1).”.