Ye Haicheng, Li Dan, Zhang Lei, Wang Yufei, Wang Cong, Jin Meng, Lin Houwen, Li Peihai, Sun Chen, Li Ning
Shandong Academy of Sciences & Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology, Jinan 250000, China.
Shandong Overseas Fisheries Association, Jinan 250000, China.
Mar Drugs. 2025 Apr 17;23(4):175. doi: 10.3390/md23040175.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, yet effective agents for its prevention and therapy remain highly limited. Epicoccin A, a significant secondary metabolite from sp., demonstrates various biological activities; however, its neuroprotective effects have not been elucidated. Here, we investigated the therapeutic potential of epicoccin A for PD by evaluating its impact on neural phenotype, reactive oxygen species (ROS) generation, and locomotor activity in PD-like zebrafish. Transcriptomic analysis and molecular docking were conducted, with key gene expressions further verified using real-time qPCR. As a result, epicoccin A notably mitigated dopaminergic neuron loss, neural vasculature deficiency, nervous system injury, ROS accumulation, locomotor impairments, and abnormal expressions of hallmark genes associated with PD and oxidative stress. Underlying mechanism investigation indicated epicoccin A may alleviate PD-like symptoms by activating PINK1/Parkin-dependent mitophagy, as evidenced by the reversal of aberrant gene expressions related to the pink1/parkin pathway and its upstream mTOR/FoxO pathway following epicoccin A co-treatments. This finding was further confirmed by the robust interactions between epicoccin A and these mitophagy regulators. Our results suggest that epicoccin A relieves PD symptoms by activating pink1/parkin-dependent mitophagy and inhibiting excessive oxidative stress, highlighting its potential as a therapeutic approach for PD.
帕金森病（PD）是第二常见的神经退行性疾病，但其预防和治疗的有效药物仍然极为有限。表球壳菌素A是一种从[具体菌种]中提取的重要次生代谢产物，具有多种生物活性；然而，其神经保护作用尚未得到阐明。在此，我们通过评估表球壳菌素A对帕金森病样斑马鱼神经表型、活性氧（ROS）生成和运动活性的影响，研究了其对帕金森病的治疗潜力。进行了转录组分析和分子对接，并使用实时定量PCR进一步验证关键基因表达。结果显示，表球壳菌素A显著减轻了多巴胺能神经元损失、神经血管缺陷、神经系统损伤、ROS积累、运动障碍以及与帕金森病和氧化应激相关的标志性基因的异常表达。潜在机制研究表明，表球壳菌素A可能通过激活PINK1/Parkin依赖性线粒体自噬来缓解帕金森病样症状，这在表球壳菌素A联合处理后与pink1/parkin途径及其上游mTOR/FoxO途径相关的异常基因表达的逆转中得到了证实。表球壳菌素A与这些线粒体自噬调节因子之间的强烈相互作用进一步证实了这一发现。我们的结果表明，表球壳菌素A通过激活pink1/parkin依赖性线粒体自噬和抑制过度氧化应激来缓解帕金森病症状，突出了其作为帕金森病治疗方法的潜力。
