Tarik Zahra,b,y , Vijay K. Bodac,d,y , Jian Gee,f,y , Lexiang Yua,g , Zhongzhi Wuc,d , Jianwen Quee,f,h, *, Wei Lic,d, *, Li Qianga,g, *

a Naomi Berrie Diabetes Center, Columbia University, New York, NY 10032, USA

b Department of Molecular Pharmacology and Therapeutics, Columbia University, New York, NY 10032, USA

c Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA

d Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA

e Division of Digestive and Liver Diseases, Columbia University, New York, NY 10032, USA

f Center for Human Development, Columbia University, New York, NY 10027, USA

g Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA

h Department of Medicine, Columbia University, New York, NY 10032, USA

*Corresponding authors.

E-mail addresses: 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。 (Jianwen Que), 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。 (Wei Li), 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。 (Li Qiang).

These authors made equal contributions to this work.

Peer review under the responsibility of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Received 22 October 2023; received in revised form 13 December 2023; accepted 5 January 2024

KEY WORDS Estrogen receptor b; Aging; Metabolism; Skin injury; Muscle metabolism; Small molecule conjugates; Regeneration; Adiposity

Hanan Khojah a , Shaima R. Ahmed a,* , Shahad Y. Alharbi a , Kholood K. AlSabeelah a ,

Hatham Y. Alrayyes a , Kadi B. Almusayyab a , Shahad R. Alrawiliy a , Raghad M. Alshammari a ,

Sumera Qasim b

a Department of Pharmacognosy, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia

b Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia

Corresponding author at: College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.

E-mail address: 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.R. Ahmed)

ARTICLE INFO

Keywords:

Launaea procumbens

Anti-aging

ADMET

Docking

ABSTRACT

Aging is a natural process that occurs in all living organisms. Particularly, the skin embodies aging since it serves as a barrier between the body and its surroundings. Previously, we reported the wound healing effect of Launaea procumbens and identified compounds therein. The study aims to explore the skin anti-aging properties of the plant extract. To that effect, the antioxidant potential of L. procumbens methanolic extract (LPM) was assessed using two complementary DPPH and FRAP assays. The enzyme inhibitory effect of the extract on collagenase, elastase, hyaluronidase, and tyrosinase was evaluated to assess the direct skin anti-aging effects. Similarly, the anti-inflammatory activity was evaluated to explore the indirect anti-aging effects via the assessment of extract inhibitory effects on cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). In addition, ADMET and molecular docking studies were performed to explore the interaction mechanisms of identified compounds in LPM with target enzymes. LPM demonstrated significant antioxidant activity in DPPH (IC50 = 29.08 µg/mL) and FRAP (1214.67 µM FeSO4/g extract) assays. Plant extract showed significant inhibition of collagenase, elastase, hyaluronidase, and tyrosinase (IC50 = 52.68, 43.76, 31.031, and 37.13 µg/mL, respectively). The extract demonstrated significant COX-2 and 5-LOX inhibition capacity with IC50 values of 8.635 and 10.851 µg/mL, respectively. The molecular docking study revealed the high potential of the identified compounds to bind to the active sites of enzymes crucially involved in the skin aging process. ADMET analysis of the compounds revealed their good absorption, distribution, and metabolism profiles, and they were found to be safe as well. Study findings suggest L. procumbens as a promising source for the development of natural skin anti-aging and anti oxidant compounds. This, in turn, may facilitate its incorporation into cosmetic formulations after further investigation.

Nahid Amini | Christina Osterlund | Jessen Curpen | Virginie Lafon-Kolb | Thibaud Richard | Lene Visdal-Johnsen Global Research and Development, Oriflame Cosmetics, Stockholm, Sweden

Correspondence: Nahid Amini (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。)

Received: 19 September 2024 | Revised: 15 November 2024 | Accepted: 25 November 2024

Funding: The authors received no specific funding for this work.

Keywords: collagen | data mining | dermal density | Glycyrrhiza uralensis | phytoestrogen

ABSTRACT

Background: The dermal extracellular matrix (ECM) is a dynamic scaffold composed mainly of proteins, with collagen as the key structural component providing resilience and support to the skin. Post-menopause, declining estrogen levels lead to a significant reduction in skin health, notably a 30% decrease in collagen types I and III within 5 years.

Aim: To discover natural extracts that stimulate collagen production.

Methods: We utilized PathwayStudio to analyze protein–protein interactions and identify regulators of essential collagen types. Our study assessed Glycyrrhiza uralensis extract's ability to boost collagen production and enhance dermal density both in vitro and in vivo.

Results: PathwayStudio analysis highlighted phytoestrogens including glycyrrhizin, isoliquiritigenin, liquiritigenin, liquiritin, and glabrol, as potential candidates. Liquorice rhizome (G. uralensis), used in traditional Chinese medicine, is rich in phytoestrogens like liquiritigenin. The G. uralensis extract increased collagen I and III gene expression and pro-collagen I protein levels in human dermal fibroblasts and inhibited UVB and pollution-induced matrix metalloproteinase-1 (MMP1) production. In an in vivo study, a topical formulation containing the extract significantly improved dermal density after 56days, measured by the DUB SkinScanner.

Conclusions: These findings suggest G. uralensis extract as a promising agent for enhancing collagen production and skin health, particularly in postmenopausal women. Further research is needed to explore its mechanisms and long-term effects.

Trung Quang Nguyen 1 , Thinh Van Pham 2 , Yusuf Andriana 3 and Minh Ngoc Truong 4,5,*

1 Institute of Environmental Science and Public Health, 18 Hoang Quoc Viet Street, Cau Giay, Hanoi 11353, Vietnam; 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。

2 Faculty of Tourism and Culinary, Ho Chi Minh City University of Industry and Trade, Ho Chi Minh City 70000, Vietnam; 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。

3 Research Center for Appropriate Technology, Indonesian Institute of Sciences, Subang 41213, Indonesia; 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。

4 Center for High Technology Research and Development, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Street, Cau Giay, Hanoi 100000, Vietnam

5 Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Street, Cau Giay, Hanoi 100000, Vietnam

* 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。

Academic Editor: Shige Wang

Received: 9 December 2024

Revised: 23 December 2024

Accepted: 25 December 2024

Published: 3 January 2025

Citation: Nguyen, T.Q.; Van Pham, T.; Andriana, Y.; Truong, M.N. Cordyceps militaris-Derived Bioactive Gels:

Therapeutic and Anti-Aging Applications in Dermatology. Gels 2025, 11, 33. https://doi.org/ 10.3390/gels11010033

Copyright: © 2025 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: Cordyceps militaris is a medicinal mushroom widely utilized in traditional East Asian medicine, recognized for its diverse therapeutic properties. This review explores the potential of C. militaris-derived bioactive gels for applications in dermatology and skincare, with a particular focus on their therapeutic and anti-aging benefits. In response to the rising incidence of skin cancers and the growing demand for natural bioactive ingredients, C. militaris has emerged as a valuable source of functional compounds, including cordycepin, polysaccharides, and adenosine. These compounds exhibit multiple bioactivities, including apoptosis induction, cell cycle arrest, and anti-inflammatory effects, which have been shown to be particularly effective against melanoma and other skin cancers. Additionally, the antioxidant properties of C. militaris enhance skin resilience by scavenging reactive oxygen species, reducing oxidative stress, and promoting collagen synthesis, thereby addressing skin health and anti-aging requirements. The potential for incorporating C. militaris compounds into gel-based formulations for skincare is also ex amined, either as standalone bioactives or in combination with synergistic ingredients. Emphasis is placed on the necessity of clinical trials and standardization to establish the safety, efficacy, and reproducibility of such applications. By providing a safer alternative to synthetic agents, C. militaris-derived bioactive gels represent a promising advancement in dermatology and skincare.

Keywords: anti-aging; bioactive compounds; Cordyceps militaris; dermatology; skincare; therapeutic properties