Seongsu Kang 1 , Jiwon Park 1 , Zhihong Cheng 2 , Sanghyun Ye 1 , Seung-Hyun Jun 1,* and Nae-Gyu Kang 1,*

1 LG Household and Health Care R&D Center, Seoul 07795, Republic of Korea; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (S.K.); 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.P.); 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (S.Y.)

2 Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai 201203, China; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

* Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (S.-H.J.); 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (N.-G.K.); Tel.: +82-2-6980-1239 (S.-H.J.); +82-2-6980-1533 (N.-G.K.)

Citation: Kang, S.; Park, J.; Cheng, Z.; Ye, S.; Jun, S.-H.; Kang, N.-G. Novel Approach to Skin Anti-Aging: Boosting Pharmacological Effects of Exogenous Nicotinamide Adenine Dinucleotide (NAD+ ) by Synergistic Inhibition of CD38 Expression. Cells 2024, 13, 1799.

https://doi.org/10.3390/ cells13211799

Academic Editor: Paweł Kordowitzki

Received: 8 October 2024

Revised: 28 October 2024

Accepted: 28 October 2024

Published: 30 October 2024

Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Abstract: Nicotinamide adenine dinucleotide (NAD+ ) is indispensable for the regulation of biological metabolism. Previous studies have revealed its role in aging and degenerative diseases, while crucially showing that supplementation with NAD+ or its precursors could ameliorate or reverse the progression of aging. Despite extensive evidence for the role and action of NAD+ in aging, its pharmacological activity on the skin, or even its mechanism, has not been elucidated. In this study, we established a novel approach to effectively utilize NAD+ for skin anti-aging by enhancing the pharmacological efficacy of exogenous NAD+ using a phytochemical complex consisting of quercetin, and enoxolone through inhibition of CD38. Through the comprehensive in vitro experiments based on human fibroblasts, we observed that exogenous NAD+ could exert protective effects against both extrinsic aging induced by ultraviolet light exposure and intrinsic aging. Additionally, we found that its effects were significantly boosted by quercetin and enoxolone. In this in-depth study, we demonstrated that these beneficial effects are mediated by improved sirtuin activation, autophagy, and mitochondrial functionality. Our approach is expected to verify the applicability of the topical application of NAD+ and offer more effective solutions for the unmet needs of patients and consumers who demand more effective anti-aging effects.

Keywords: nicotinamide adenine dinucleotide (NAD+ ); quercetin; enoxolone; anti-aging; topical application; CD38