Dai Wenyu, Deng Lifeng, He Chenyang, Fu Xiaoxia, Liu Jing, Wang Guo-Cai, Yang Jing, Zhang Yu-Bo, Xiao Fei, Wan Qin-Li
Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China; The College of Life Science and Technology, Jinan University, Guangzhou, 510632, Guangdong, China.
The College of Life Science and Technology, Jinan University, Guangzhou, 510632, Guangdong, China.
J Ethnopharmacol. 2025 Feb 27;342:119399. doi: 10.1016/j.jep.2025.119399. Epub 2025 Jan 30.
The root of Croton crassifolius Geiseler (C. crassifolius), commonly known as "Jiguxiang" in traditional Chinese medicine, is globally recognized for its ethnomedical applications in treating a spectrum of diseases. Crassifolin A (CA), a diterpenoid compound extracted from the roots of C. crassifolius, exhibits anti-herpes simplex virus (HSV), anti-viral and anti-angiogenic properties.
This study aimed to explore the effects of CA on aging and the mechanisms involved.
Utilizing Caenorhabditis elegans (C. elegans) as a model organism, we conducted a comprehensive survival analysis and evaluated aging-related phenotypes, including the period of fast body movement and body bending rates. To elucidate the molecular mechanisms of CA's impact on aging, we employed a multifaceted approach, including reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, and fluorescence quantification of transgenic reporter strains.
Our findings demonstrated that CA significantly prolonged both the lifespan and healthspan of C. elegans. The survival benefits conferred by CA were found to correlate with the activation of several key aging-related signaling pathways, including insulin/insulin-like signaling pathway (IIS), dietary restriction (DR) pathway, and germline signaling pathway. Engagement of these pathways led to the activation of transcription factors DAF-16/FOXO, SKN-1/NRF2, HSF-1 and HLH-30/TFEB, as well as the nuclear receptor DAF-12. Consequently, this activation cascade prompted an upregulation of autophagy, a cellular process associated with the maintenance of cellular homeostasis and longevity.
Our study delineates novel mechanisms underlying anti-aging strategies, establishing a conceptual framework for the exploitation and advancement of traditional Chinese medicinal herbs as potential therapeutic agents in the fight against aging and its associated pathologies.
厚叶巴豆（Croton crassifolius Geiseler）的根，在传统中医中俗称“鸡骨香”，因其在治疗多种疾病的民族医学应用而在全球范围内得到认可。厚叶巴豆素A（CA）是从厚叶巴豆根中提取的一种二萜类化合物，具有抗单纯疱疹病毒（HSV）、抗病毒和抗血管生成特性。
本研究旨在探讨CA对衰老的影响及其相关机制。
以秀丽隐杆线虫（Caenorhabditis elegans，C. elegans）为模式生物，我们进行了全面的生存分析，并评估了与衰老相关的表型，包括快速身体运动期和身体弯曲率。为了阐明CA对衰老影响的分子机制，我们采用了多方面的方法，包括逆转录定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹法和转基因报告菌株的荧光定量分析。
我们的研究结果表明，CA显著延长了秀丽隐杆线虫的寿命和健康寿命。发现CA带来的生存益处与几种关键的衰老相关信号通路的激活有关，包括胰岛素/胰岛素样信号通路（IIS）、饮食限制（DR）通路和生殖系信号通路。这些通路的参与导致转录因子DAF-16/FOXO、SKN-1/NRF2、HSF-1和HLH-30/TFEB以及核受体DAF-12的激活。因此，这种激活级联促使自噬上调，自噬是一种与维持细胞稳态和长寿相关的细胞过程。
我们的研究描绘了抗衰老策略的新机制，为开发和推进传统中草药作为对抗衰老及其相关疾病的潜在治疗药物建立了概念框架。
