Epicoccin A Ameliorates PD-like Symptoms in Zebrafish: Enhancement of PINK1/Parkin-Dependent Mitophagy and Inhibition of Excessive Oxidative Stress
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 <i>Exserohilum</i> sp., demonstrates various biological activities; however, i...
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2025-04-01
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| author | Haicheng Ye Dan Li Lei Zhang Yufei Wang Cong Wang Meng Jin Houwen Lin Peihai Li Chen Sun Ning Li |
| author_facet | Haicheng Ye Dan Li Lei Zhang Yufei Wang Cong Wang Meng Jin Houwen Lin Peihai Li Chen Sun Ning Li |
| author_sort | Haicheng Ye |
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| description | 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 <i>Exserohilum</i> 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. |
| format | Article |
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| institution | DOAJ |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Marine Drugs |
| spelling | doaj-art-fb2aa3fd50a94cae904acbe784cc1ad32025-08-20T03:13:55ZengMDPI AGMarine Drugs1660-33972025-04-0123417510.3390/md23040175Epicoccin A Ameliorates PD-like Symptoms in Zebrafish: Enhancement of PINK1/Parkin-Dependent Mitophagy and Inhibition of Excessive Oxidative StressHaicheng Ye0Dan Li1Lei Zhang2Yufei Wang3Cong Wang4Meng Jin5Houwen Lin6Peihai Li7Chen Sun8Ning Li9Shandong 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, ChinaShandong 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, ChinaShandong Overseas Fisheries Association, Jinan 250000, ChinaKey Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission & Guangxi Key Laboratory of Chemistry and Engineering of Forest Products/Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, Guangxi Minzu University, Nanning 530000, ChinaKey Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission & Guangxi Key Laboratory of Chemistry and Engineering of Forest Products/Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, Guangxi Minzu University, Nanning 530000, ChinaShandong 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, ChinaResearch Center for Marine Drugs, State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, ChinaShandong 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, ChinaShandong 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, ChinaShandong 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, ChinaParkinson’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 <i>Exserohilum</i> 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.https://www.mdpi.com/1660-3397/23/4/175neuroprotective effectmarine-derived fungusMPTPα-synucleinROStranscriptome analysis |
| spellingShingle | Haicheng Ye Dan Li Lei Zhang Yufei Wang Cong Wang Meng Jin Houwen Lin Peihai Li Chen Sun Ning Li Epicoccin A Ameliorates PD-like Symptoms in Zebrafish: Enhancement of PINK1/Parkin-Dependent Mitophagy and Inhibition of Excessive Oxidative Stress Marine Drugs neuroprotective effect marine-derived fungus MPTP α-synuclein ROS transcriptome analysis |
| title | Epicoccin A Ameliorates PD-like Symptoms in Zebrafish: Enhancement of PINK1/Parkin-Dependent Mitophagy and Inhibition of Excessive Oxidative Stress |
| title_full | Epicoccin A Ameliorates PD-like Symptoms in Zebrafish: Enhancement of PINK1/Parkin-Dependent Mitophagy and Inhibition of Excessive Oxidative Stress |
| title_fullStr | Epicoccin A Ameliorates PD-like Symptoms in Zebrafish: Enhancement of PINK1/Parkin-Dependent Mitophagy and Inhibition of Excessive Oxidative Stress |
| title_full_unstemmed | Epicoccin A Ameliorates PD-like Symptoms in Zebrafish: Enhancement of PINK1/Parkin-Dependent Mitophagy and Inhibition of Excessive Oxidative Stress |
| title_short | Epicoccin A Ameliorates PD-like Symptoms in Zebrafish: Enhancement of PINK1/Parkin-Dependent Mitophagy and Inhibition of Excessive Oxidative Stress |
| title_sort | epicoccin a ameliorates pd like symptoms in zebrafish enhancement of pink1 parkin dependent mitophagy and inhibition of excessive oxidative stress |
| topic | neuroprotective effect marine-derived fungus MPTP α-synuclein ROS transcriptome analysis |
| url | https://www.mdpi.com/1660-3397/23/4/175 |
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