{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:14:31Z","timestamp":1787318071103,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Qi-Huang Chief Scientist Program of National Administration of Traditional Chinese Medicine (2020)","award":["82130111"],"award-info":[{"award-number":["82130111"]}]},{"name":"Key Program of the National Natural Science Foundation of China","award":["82130111"],"award-info":[{"award-number":["82130111"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cicadae Periostracum (CP) is a traditional Chinese animal-derived medicine with the potential to treat Parkinson\u2019s disease (PD). This study aims to explore the pharmacodynamic mechanisms of CP against PD-based on metabolomics technology and provide a theoretical basis for developing new anti-PD medicine. First, MPP+-induced SH-SY5Y cells were used to evaluate the anti-PD activity of CP. In the animal study, an MPTP-induced PD mouse model was employed to assess CP\u2019s therapeutic effects. Immunofluorescence (IF) staining and Western blotting (WB) were used to evaluate its neuroprotective activity on neurons. A Serum metabolomics analysis was conducted to examine CP\u2019s regulatory effects on metabolites and to identify vital metabolic pathways. Finally, cellular experiments were performed to validate the critical pathways. Cellular activity experiments demonstrated that CP mitigates MPP+-induced SH-SY5Y cytotoxicity, inhibits apoptosis, and restores mitochondrial homeostasis. Animal experiments revealed that CP significantly alleviates dyskinesia in PD mice, enhances motor performance, and restores neuronal integrity while reducing \u03b1-synuclein (\u03b1-syn) aggregation in the striatum (STR), showing its strong anti-PD effect. Metabolomic analysis revealed that CP can significantly improve the metabolic disorders of ten biomarkers that are mainly involved in amino acid metabolism and fatty acid \u03b2-oxidation and are closely related to oxidative stress pathways. Finally, pathway verification was performed, and the results show that CP exerted neuroprotective effects against PD through the dual signaling pathways of Bcl-2\/Bax\/Caspase-3 and Nrf2\/HO-1. This study provides a comprehensive strategy for elucidating the mechanisms by which CP exerts its therapeutic effects against PD, highlighting its potential in developing anti-PD drugs.<\/jats:p>","DOI":"10.3390\/ijms26020544","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T03:48:11Z","timestamp":1736480891000},"page":"544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacodynamic Mechanisms of Cicadae Periostracum in Parkinson\u2019s Disease: A Metabolomics-Based Study"],"prefix":"10.3390","volume":"26","author":[{"given":"Mengmeng","family":"Li","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyu","family":"Xiong","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifei","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Wei","sequence":"additional","affiliation":[{"name":"Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2447-170X","authenticated-orcid":false,"given":"Hanze","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Qiao","sequence":"additional","affiliation":[{"name":"Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cger.2019.08.002","article-title":"Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology","volume":"36","author":"Simon","year":"2020","journal-title":"Clin. Geriatr. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"661","DOI":"10.20344\/amp.11978","article-title":"Parkinson\u2019s Disease: Clinical Review and Update","volume":"32","author":"Cabreira","year":"2019","journal-title":"Acta Med. Port."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and Treatment of Parkinson Disease: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S1474-4422(16)30230-7","article-title":"The epidemiology of Parkinson\u2019s disease: Risk factors and prevention","volume":"15","author":"Ascherio","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Degirmenci, Y., Angelopoulou, E., Georgakopoulou, V.E., and Bougea, A. (2023). Cognitive Impairment in Parkinson\u2019s Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches. Medicina, 59.","DOI":"10.20944\/preprints202308.1550.v1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106086","DOI":"10.1016\/j.fitote.2024.106086","article-title":"Pharmacodynamical research of extracts and compounds in traditional Chinese medicines for Parkinson\u2019s disease","volume":"177","author":"Li","year":"2024","journal-title":"Fitoterapia"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Tang, X.M., Guo, J.L., Chen, L., and Ho, P.C. (2020). Application for proteomics analysis technology in studying animal-derived traditional Chinese medicine: A review. J. Pharm. Biomed. Anal., 191.","DOI":"10.1016\/j.jpba.2020.113609"},{"key":"ref_8","first-page":"1934578X19850019","article-title":"Cicadamides A and B,N-Acetyldopamine Dimers From the InsectPeriostracum cicadae","volume":"14","author":"Liu","year":"2019","journal-title":"Nat. Prod. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Cao, X.C., Guo, M.F., Han, Y., Fan, Y.T., Zhu, J.H., Zhu, H., Xu, J.D., Shen, H., Zhou, G.R., and Mao, Q. (2021). Systematic metabolite profiling of N-acetyldopamine oligomers from Cicadae Periostracum in rats by ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. J. Pharm. Biomed. Anal., 192.","DOI":"10.1016\/j.jpba.2020.113665"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.phytol.2014.12.002","article-title":"N-Acetyldopamine derivatives from Periostracum Cicadae","volume":"11","author":"Yang","year":"2015","journal-title":"Phytochem. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, D., Wu, T., Jin, J., Si, Y., Wang, Y., Ding, X., Guo, T., and Wei, W. (2024). Periostracum Cicadae Extract and N-Acetyldopamine Regulate the Sleep-Related Neurotransmitters in PCPA-Induced Insomnia Rats. Molecules, 29.","DOI":"10.3390\/molecules29153638"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5797512","DOI":"10.1155\/2019\/5797512","article-title":"Cicadidae Periostracum, the Cast-Off Skin of Cicada, Protects Dopaminergic Neurons in a Model of Parkinson\u2019s Disease","volume":"2019","author":"Lim","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"G\u0105tarek, P., Sekulska-Nalewajko, J., Bobrowska-Korczaka, B., Pawe\u0142czyk, M., Jastrz\u0119bski, K., G\u0142\u0105bi\u0144ski, A., and Ka\u0142u\u017cna-Czapli\u0144ska, J. (2022). Plasma Metabolic Disturbances in Parkinson\u2019s Disease Patients. Biomedicines, 10.","DOI":"10.3390\/biomedicines10123005"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13024-023-00694-5","article-title":"Untargeted serum metabolomics reveals novel metabolite associations and disruptions in amino acid and lipid metabolism in Parkinson\u2019s disease","volume":"18","author":"Paul","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/bs.acc.2020.09.003","article-title":"Metabolomics in Parkinson\u2019s disease","volume":"104","author":"Troisi","year":"2021","journal-title":"Adv. Clin. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/jnc.15699","article-title":"Neurochemical, histological, and behavioral profiling of the acute, sub-acute, and chronic MPTP mouse model of Parkinson\u2019s disease","volume":"164","author":"Santoro","year":"2023","journal-title":"J. Neurochem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Nebrisi, E.E. (2021). Neuroprotective Activities of Curcumin in Parkinson\u2019s Disease: A Review of the Literature. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011248"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nagatsu, T., Nakashima, A., Watanabe, H., Ito, S., and Wakamatsu, K. (2022). Neuromelanin in Parkinson\u2019s Disease: Tyrosine Hydroxylase and Tyrosinase. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202203.0274.v1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13024-021-00425-8","article-title":"Comprehensive metabolic profiling of Parkinson\u2019s disease by liquid chromatography-mass spectrometry","volume":"16","author":"Shao","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e14411","DOI":"10.1111\/cns.14411","article-title":"The potential role of glucose metabolism, lipid metabolism, and amino acid metabolism in the treatment of Parkinson\u2019s disease","volume":"30","author":"Li","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S1097-2765(03)00105-9","article-title":"An integrated stress response regulates amino acid metabolism and resistance to oxidative stress","volume":"11","author":"Harding","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_22","first-page":"461","article-title":"The role of oxidative stress in Parkinson\u2019s disease","volume":"3","author":"Dias","year":"2013","journal-title":"J. Park. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.pneurobio.2013.04.004","article-title":"Mitochondrial dysfunction and oxidative stress in Parkinson\u2019s disease","volume":"106\u2013107","author":"Subramaniam","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-immunol-073119-095439","article-title":"Caspases in Cell Death, Inflammation, and Pyroptosis","volume":"38","author":"Kesavardhana","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.neuro.2021.10.003","article-title":"Baicalein protects against MPP(+)\/MPTP-induced neurotoxicity by ameliorating oxidative stress in SH-SY5Y cells and mouse model of Parkinson\u2019s disease","volume":"87","author":"Song","year":"2021","journal-title":"Neurotoxicology"},{"key":"ref_26","first-page":"3409","article-title":"Species of Chinese materia medica resources based on the fourth national survey of Chinese materia medica resources","volume":"49","author":"Huang","year":"2024","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1515\/jom-2020-0052","article-title":"Animal-derived medications: Cultural considerations and available alternatives","volume":"121","author":"Babos","year":"2021","journal-title":"J. Osteopath. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Xie, X., Guo, H., Liu, J., Wang, J., Li, H., and Deng, Z. (2023). Edible and Medicinal Progress of Cryptotympana atrata (Fabricius) in China. Nutrients, 15.","DOI":"10.3390\/nu15194266"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Thapa, P., Gu, Y., Kil, Y.S., Baek, S.C., Kim, K.H., Han, A.R., Seo, E.K., Choi, H., Chang, J.H., and Nam, J.W. (2020). N-Acetyldopamine derivatives from Periostracum Cicadae and their regulatory activities on Th1 and Th17 cell differentiation. Bioorg. Chem., 102.","DOI":"10.1016\/j.bioorg.2020.104095"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"20690","DOI":"10.1021\/acs.jafc.3c04851","article-title":"Dimeric N-Acetyldopamine Derivatives Featuring a Seco-Benzene System from the Insects Aspongopus chinensis and Periostracum cicadae","volume":"71","author":"Yan","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7826","DOI":"10.1016\/j.bmc.2006.07.063","article-title":"Antioxidant and anti-inflammatory activities of N-acetyldopamine dimers from Periostracum Cicadae","volume":"14","author":"Xu","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1002\/mas.21562","article-title":"Challenges and emergent solutions for LC-MS\/MS based untargeted metabolomics in diseases","volume":"37","author":"Cui","year":"2018","journal-title":"Mass. Spectrom. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1002\/mds.25644","article-title":"Metabolomics and the search for biomarkers in Parkinson\u2019s disease","volume":"28","author":"Amara","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40170-016-0151-y","article-title":"Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool","volume":"4","author":"Brown","year":"2016","journal-title":"Cancer Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ymgme.2022.03.004","article-title":"Comparative metabolomics in the Pah(enu2) classical PKU mouse identifies cerebral energy pathway disruption and oxidative stress","volume":"136","author":"Dobrowolski","year":"2022","journal-title":"Mol. Genet. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/MCO.0000000000000704","article-title":"Essential amino acid formulations to prevent mitochondrial dysfunction and oxidative stress","volume":"24","author":"Ruocco","year":"2021","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/544\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:26:20Z","timestamp":1759919180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,10]]},"references-count":36,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26020544"],"URL":"https:\/\/doi.org\/10.3390\/ijms26020544","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,10]]}}}