Juewon Kim1,

*, Hyeryung Kim2 , Woo-Young Seo3 , Eunji Lee3 and Donghyun Cho4

1 Department of Physiology, Konkuk University College of Medicine, Chungju 27478,

2 GENINUS Inc., Seoul 05836,

3 ABIOTECH Co., Ltd., Suwon 16675,

4 HEM pharma, Suwon 16229, Republic of Korea

Abstract

Longevity genes and senescence-related signaling proteins are crucial targets in aging research, which aims to enhance the healthy period and quality of life. Identifying these target proteins remains challenging because of the need for precise categorization and validation methods. Our multifaceted approach combined bioinformatics with transcriptomic data to identify collagen as a key element associated with the lifespan of the model organism, Caenorhabditis elegans. By analyzing transcriptomic data from long-lived mutants that involved mechanisms such as antioxidation, dietary restriction, and genetic background, we identified collagen as a common longevity-associated gene. We validated these findings by confirming that collagen peptides positively affect lifespan, thereby strengthening the validity of the target. Further verification through healthspan factors in C. elegans and functional assays in skin fibroblasts provided additional evidence of the role of collagen in organismal aging. Specifically, our study revealed that collagen type VII is a significant target protein for mitigating age-related decline. By validating these findings across different aging models and cell-based studies, we present compelling evidence for the anti-aging effects of collagen type VII, highlighting its potential as a target for promoting healthy aging. This study proposes that collagen not only serves as an indicative marker of organismal longevity across various senescence-related signaling pathways, but also offers a mechanistic understanding of skin degeneration. Consequently, collagen is an effective target for interventions aimed at mitigating skin aging. This study underscores the potential of collagen type VII (bonding collagen T7) as a therapeutic target for enhancing skin health and overall longevity.

Key Words: Collagen VII, Healthspan, C. elegans, Skin aging, Bonding collagen

https://doi.org/10.4062/biomolther.2024.127

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received Aug 1, 2024 Revised Sep 10, 2024 Accepted Sep 30, 2024

Published Online Oct 21, 2024

*

Corresponding Author

E-mail: 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。

Tel: +82-43-840-3728, Fax: +82-2-2049-6195

Yajing Li , Lan Xiang and Jianhua Qi *

College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, 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。 (Y.L.); 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。 (L.X.)

* 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 Editors: Marina Garcia-Macia and Álvaro F. Fernández

Received: 18 February 2025

Revised: 5 March 2025

Accepted: 5 March 2025

Published: 7 March 2025

Citation: Li, Y.; Xiang, L.; Qi, J. Procyanidin A1 from Peanut Skin Exerts Anti-Aging Effects and Attenuates Senescence via Antioxidative Stress and Autophagy Induction. Antioxidants 2025, 14, 322.

https://doi.org/10.3390/ antiox14030322

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: The aging population is steadily increasing, with aging and age-related diseases serving as major risk factors for morbidity, mortality, and economic burden. Peanuts, known as the “longevity nut” in China, have been shown to offer various health benefits, with peanut skin extract (PSE) emerging as a key compound of interest. This study investigates the bioactive compound in PSE with anti-aging potential and explores its underlying mechanisms of action. Procyanidin A1 (PC A1) was isolated from PSE, guided by the K6001 yeast replicative lifespan model. PC A1 prolonged the replicative lifespan of yeast and the yeast-like chronological lifespan of PC12 cells. To further confirm its anti-aging effect, cellular senescence, a hallmark of aging, was assessed. In senescent cells induced by etoposide (Etop), PC A1 alleviated senescence by reducing ROS levels, decreasing the percentage of senescent cells, and restoring proliferative capacity. Transcriptomics analysis revealed that PC A1 induced apoptosis, reduced senescence-associated secretory phenotype (SASP) factors, and modulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. The antioxidative capacity of PC A1 was also evaluated, showing enhanced resistance to oxidative stress in PC12 cells by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) activity. Moreover, PC A1 induced autophagy, as evidenced by an increase in fluorescence-labeled autophagic compartments and confirmation via Western blot analysis of autophagy-related proteins. In addition, the treatment of an autophagy inhibitor abolished the antioxidative stress and senescence-alleviating effects of PC A1. These findings reveal that PC A1 extended lifespans and alleviated cellular senescence by enhancing oxidative stress resistance and inducing autophagy, positioning it as a promising candidate for further exploration as a geroprotective agent.

Keywords: aging; peanut skin; procyanidin A1; cell senescence; antioxidative stress; autophagy; PI3K/Akt signaling pathway

Chaiyawat Aonsri 1,2 , Sompop Kuljarusnont 3

and Duangjai Tungmunnithum 4,5,*

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand; 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 Unit of Compounds Library for Drug Discovery, Mahidol University, Bangkok 10400, Thailand

3 Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; 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 Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand

5 Le Studium Institute for Advanced Studies, 1 Rue Dupanloup, 45000 Orléans, France 

* 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。; Tel./Fax: +66-26448696

Academic Editors: Lina Raudone,˙ Mindaugas Liaudanskas and Sonata Trumbeckaite

Received: 8 January 2025

Revised: 20 February 2025

Accepted: 24 February 2025

Published: 26 February 2025

Citation: Aonsri, C.; Kuljarusnont, S.; Tungmunnithum, D. Discovering Skin Anti-Aging Potentials of the Most Abundant Flavone Phytochemical Compound Reported in Siam Violet Pearl, a Medicinal Plant from Thailand by In Silico and In Vitro Assessments. Antioxidants 2025, 14, 272. https://doi.org/10.3390/ antiox14030272

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: Currently, nutraceuticals and functional food/cosmeceutical sectors are seeking natural molecules to develop various types of phytopharmaceutical products. Flavonoids have been reported in antioxidant and many medical/pharmacological activities. Monochoria angustifolia or Siam violet pearl medicinal plant is the newest species of the genus Monochoria C. Presl, which have long been consumed as food and herbal medicines. Though previous work showed that apigenin-7-O-glucoside is the most abundant antioxidant phytochemical found in this medicinal plant, the report on anti-aging activity is still lacking and needs to be filled in. The objective of this work is to explore anti-aging capacities of the most abundant antioxidant phytochemical reported in this plant using both in silico and in vitro assessments. In addition, pharmacokinetic properties were predicted. Interestingly, the results from both in silico and in vitro analysis showed a similar trend that apigenin-7- O-glucoside is a potential anti-aging agent against three enzymes. The pharmacokinetic properties, such as adsorption, distribution, metabolism, excretion and toxicity (ADMET), of this compound are also provided in this work. The current study is also the first report on anti-aging properties of this Thai medicinal plant. However, the safety and efficacy of future developed products from this compound and clinical study should be determined in the future.

Keywords: flavone; Monochoria angustifolia; flavonoids; medicinal plants; anti-aging; molecular modeling; pharmacological activity; medical benefits

Yijia Zhang1 | Xueer Wang1 | Jianyuan Huang1 | Xinyue Zhang1 | Lingwei Bu1 |

Yarui Zhang1 | Fengting Liang1 | Shenhua Wu1 | Min Zhang1 | Lu Zhang2 |

Lin Zhang1

1 GDMPA Key Laboratory of key Technologies for Cosmetics Safety and Efficacy Evaluation, NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

2 Guangdong Provincial Key Laboratory of Proteomics, Department of Pathophysiology, Key Laboratory of Mental Health of the Ministry of Education, School of Basic Medical Sciences, Center for Orthopaedic Surgery of the Third Affiliated Hospital, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, China

Correspondence

Lu Zhang, Guangdong Provincial Key Laboratory of Proteomics, Department of Pathophysiology, Key Laboratory of Mental Health of the Ministry of Education, School of Basic Medical Sciences, Center for Orthopaedic Surgery of the Third Affiliated Hospital, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, China.

Email: 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。 Lin Zhang, GDMPA Key Laboratory of key Technologies for Cosmetics Safety and Efficacy Evaluation, NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Email: 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。

Funding information

National Natural Science Foundation of China, Grant/Award Number: 82073417, 81872514 and 81971297; GDMPA Key Laboratory Project of Scientific and Technological Innovation, Grant/Award

Number: 2023ZDZ12; Guangdong Basic and Applied Basic Research Foundation, Grant/Award Number: 2022A1515010768, 2023A1515012480 and 2024A121301233

Abstract

Skin aging has been associated with the onset of various skin issues, and recent studies have identified an increase in Cdc42 activity in naturally aging mice. While previous literature has suggested that CASIN, a specific inhibitor of Cdc42 activity, may possess anti-aging properties, its specific effects on the epidermis and dermis, as well as the underlying mechanisms in naturally aging mice, remain unclear. Our study revealed that CASIN demonstrated the ability to increase epidermal and dermal thickness, enhance dermal-epidermal junction, and stimulate collagen and elastic fiber synthesis in 9-, 15-, and 24-month-old C57BL/6 mice in vivo. Moreover, CASIN was found to enhance the proliferation, differentiation, and colony formation and restore the cytoskeletal morphology of primary keratinocytes in naturally aging skin in vitro. Furthermore, the anti-aging properties of CASIN on primary fibroblasts in aging mice were mediated by the ribosomal protein RPL4 using proteomic sequencing, influencing collagen synthesis and cytoskeletal morphology both in vitro and in vivo. Meanwhile, both subcutaneous injection and topical application exhibited anti-aging effects for a duration of 21 days. Additionally, CASIN exhibited anti-inflammatory properties, while reduced expression of RPL4 was associated with increased inflammation in the skin of naturally aging mice. Taken together, our results unveil a novel function of RPL4 in skin aging, providing a foundational basis for future investigations into ribosomal proteins. And CASIN shows promise as a potential anti-aging agent for naturally aging mouse skin, suggesting potential applications in the field.

KEYWORDS

CASIN, Cdc42, fibroblast, keratinocyte, ribosome, skin aging