Kim Hyemin, Lee Saebyeol, Kim Hak Kyun, Park Sang-Kyu
Department of Medical Sciences, General Graduate School, Soonchunhyang University, Asan, Republic of Korea.
Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
Anim Cells Syst (Seoul). 2025 Aug 22;29(1):544-555. doi: 10.1080/19768354.2025.2549756. eCollection 2025.
Xanthoxyline, a plant-derived phytochemical, has anti-bacterial, anti-fungal, and anti-cancer activities. We intended to investigate the effect of xanthoxyline on the response to oxidative stress, aging, and Parkinson's disease. The effects of dietary supplementation with xanthoxyline on stress response and aging were examined using as a model system. Genetic analysis using mutants, RNAi, and quantitative RT-PCR was performed to identify underlying mechanism involved in xanthoxyline-induced longevity. Animal disease models were employed to examine the effect of xanthoxyline on Parkinson's disease. Xanthoxyline increased resistance to the oxidative stress induced by HO. The mean lifespan of worms was significantly increased by supplementation with xanthoxyline. The lifespan-extending activity of xanthoxyline was not accompanied by reduced fertility. Xanthoxyline delayed the age-related decline in motility. Interestingly, the expression of two longevity-assuring genes, , and , was increased by xanthoxyline supplementation. Genetic analysis suggested that lifespan extension by xanthoxyline was mediated by activation of autophagy and required DAF-16. In a model of Parkinson's disease, degeneration of dopaminergic neurons was prevented by supplementation with xanthoxyline, in a manner dependent on DAF-16. Taken together, we concluded that xanthoxyline exerts an anti-aging activity, possibly by activating the DAF-16-dependent stress response, and reduces the risk of Parkinson's disease, in a manner mediated by DAF-16. Xanthoxyline shows promise for the development of novel nutraceuticals against aging and Parkinson's disease.
花椒碱是一种植物源植物化学物质，具有抗菌、抗真菌和抗癌活性。我们旨在研究花椒碱对氧化应激反应、衰老和帕金森病的影响。以其作为模型系统，研究了膳食补充花椒碱对应激反应和衰老的影响。利用突变体、RNA干扰和定量逆转录聚合酶链反应进行基因分析，以确定花椒碱诱导长寿的潜在机制。采用动物疾病模型研究花椒碱对帕金森病的影响。花椒碱增强了对过氧化氢诱导的氧化应激的抵抗力。补充花椒碱显著延长了线虫的平均寿命。花椒碱的寿命延长活性并未伴随着生育力的降低。花椒碱延缓了与年龄相关的运动能力下降。有趣的是，补充花椒碱可增加两个长寿保障基因（此处基因名称缺失）的表达。基因分析表明，花椒碱延长寿命是通过自噬激活介导的，且需要DAF-16。在帕金森病模型中，补充花椒碱可预防多巴胺能神经元的退化，其方式依赖于DAF-16。综上所述，我们得出结论，花椒碱可能通过激活DAF-16依赖性应激反应发挥抗衰老活性，并以DAF-16介导的方式降低帕金森病的风险。花椒碱在开发抗衰老和帕金森病的新型营养保健品方面具有前景。
