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Integr. Neurosci."],"abstract":"<jats:p>Background:Parkinson\u2019s disease (PD) is a prevalent neurodegenerative disorder hallmarked by progressive loss of midbrain dopaminergic (DA) neurons, neurite atrophy, neurotransmitter imbalance, and motor dysfunction. Therapeutic strategies targeting neuronal integrity and neuroinflammation hold translational value beyond conventional symptomatic therapies for PD. Sarsasapogenin, a natural steroidal saponin, exhibits documented neuroprotective properties in multiple neurological diseases. However, its therapeutic potential and underlying mechanisms in PD remain to be elucidated.Methods:The neuroprotective efficacy of sarsasapogenin was assessed in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse PD model and 1-methyl-4-phenylpyridinium ion (MPP+)-insulted primary cortical and dopaminergic neuronal cultures. Motor function was evaluated via a variety of behavioral tests. Survival of dopaminergic neurons was quantified using tyrosine hydroxylase (TH) immunostaining. Levels of monoamine neurotransmitters and their metabolites were measured using high-performance liquid chromatography (HPLC), while serum proinflammatory cytokines were determined using enzyme-linked immunosorbent assay (ELISA). Neurite outgrowth and neuronal viability were examined under both preventive and therapeutic treatment regimens in vitro. Potential molecular targets of sarsasapogenin were screened and identified via Drug Affinity Responsive Target Stability (DARTS) coupled with molecular docking.Results:Twenty-one-day sarsasapogenin intervention mitigated aberrant motor deficits in MPTP-treated mice, rescued TH+ dopaminergic neurons in the substantia nigra, restored homeostasis of dopamine and norepinephrine, normalized the turnover of monoamines, and decreased peripheral levels of the proinflammatory cytokines tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-1\u03b2 (IL-1\u03b2). In primary neuronal cultures, sarsasapogenin significantly ameliorated MPP+-triggered neurite atrophy and neuronal loss in both cortical and ventral mesencephalic dopaminergic neurons. DARTS screening combined with molecular docking identified serpin family H member 1 (Serpin) H1 as a candidate binding protein of sarsasapogenin, with a favorable binding affinity of \u22128.6 kcal\/mol.Conclusions:Sarsasapogenin exerts comprehensive neuroprotective effects in preclinical PD models via synergistic modulation of dopaminergic neuronal survival, neurotransmitter balance, inflammatory inhibition, and neurite outgrowth. These findings highlight sarsasapogenin as a promising multi-target candidate for PD intervention, whereas the precise functional role of Serpin H1 in mediating its neuroprotective actions warrants further in-depth investigation.<\/jats:p>","DOI":"10.31083\/jin50683","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:01:26Z","timestamp":1785409286000},"source":"Crossref","is-referenced-by-count":0,"title":["Sarsasapogenin Improves Pathological Phenotypes in MPTP\/MPP+-Induced Parkinson\u2019s Disease Models: Synergistic Actions of Neurite Outgrowth, Neurotransmitter Modulation, and Anti-Inflammation"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0864-3599","authenticated-orcid":true,"given":"Wendi","family":"Deng","sequence":"first","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Guangdong Ocean University, 524088 Zhanjiang, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1973-9413","authenticated-orcid":true,"given":"Jinfeng","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Guangdong Ocean University, 524088 Zhanjiang, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3167-1296","authenticated-orcid":true,"given":"Weixia","family":"Li","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Guangdong Ocean University, 524088 Zhanjiang, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1600-7456","authenticated-orcid":true,"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Guangdong Ocean University, 524088 Zhanjiang, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-860X","authenticated-orcid":true,"given":"Yongping","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Guangdong Ocean University, 524088 Zhanjiang, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6551-684X","authenticated-orcid":true,"given":"Zhiyou","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Guangdong Ocean University, 524088 Zhanjiang, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Arjunan SP, Kumar DK. Techniques for assessment of parkinsonism for diagnosis and rehabilitation. Springer: Berlin, Germany. 2022.","DOI":"10.1007\/978-981-16-3056-9"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Su D, Cui Y, He C, Yin P, Bai R, Zhu J, et al. Projections for prevalence of Parkinson's disease and its driving factors in 195 countries and territories to 2050: modelling study of Global Burden of Disease Study 2021. BMJ (Clinical Research Ed.). 2025; 388: e080952.","DOI":"10.1136\/bmj-2024-080952"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Rizek P, Kumar N, Jog MS. An update on the diagnosis and treatment of Parkinson disease. CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne. 2016; 188: 1157\u20131165.","DOI":"10.1503\/cmaj.151179"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Xu L, Pu J. Alpha-Synuclein in Parkinson's Disease: From Pathogenetic Dysfunction to Potential Clinical Application. Parkinson's Disease. 2016; 2016: 1720621.","DOI":"10.1155\/2016\/1720621"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Koch JC, Bitow F, Haack J, d'Hedouville Z, Zhang JN, T\u00f6nges L, et al. Alpha-Synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons. Cell Death & Disease. 2015; 6: e1811.","DOI":"10.1038\/cddis.2015.169"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Amartumur S, Nguyen H, Huynh T, Kim TS, Woo RS, Oh E, et al. Neuropathogenesis-on-chips for neurodegenerative diseases. Nature Communications. 2024; 15: 2219.","DOI":"10.1038\/s41467-024-46554-8"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Burke RE, O'Malley K. Axon degeneration in Parkinson's disease. Experimental Neurology. 2013; 246: 72\u201383.","DOI":"10.1016\/j.expneurol.2012.01.011"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Kurowska Z, Kordower JH, Stoessl AJ, Burke RE, Brundin P, Yue Z, et al. 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Respiratory Research. 2011; 12: 27.","DOI":"10.1186\/1465-9921-12-27"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Zhao Y, Liu L, Han Y, Bai J, Du G, Gao Q. Simultaneous detection of 8 monoamine neurotransmitters in the different sections of rat brains by high performance liquid chromatography with fluorescence detection. Se Pu = Chinese Journal of Chromatography. 2011; 29: 146\u2013151.","DOI":"10.3724\/sp.j.1123.2011.00146"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Mu\u00f1oz-Manchado AB, Villadiego J, Romo-Madero S, Su\u00e1rez-Luna N, Bermejo-Navas A, Rodr\u00edguez-G\u00f3mez JA, et al. Chronic and progressive Parkinson's disease MPTP model in adult and aged mice. Journal of Neurochemistry. 2016; 136: 373\u2013387.","DOI":"10.1111\/jnc.13409"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Zhang QS, Heng Y, Mou Z, Huang JY, Yuan YH, Chen NH. Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease. Acta Pharmacologica Sinica. 2017; 38: 1317\u20131328.","DOI":"10.1038\/aps.2017.49"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Jamwal S, Kumar P. Insight Into the Emerging Role of Striatal Neurotransmitters in the Pathophysiology of Parkinson's Disease and Huntington's Disease: A Review. Current Neuropharmacology. 2019; 17: 165\u2013175.","DOI":"10.2174\/1570159X16666180302115032"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Tiwari PC, Pal R. The potential role of neuroinflammation and transcription factors in Parkinson disease. Dialogues in Clinical Neuroscience. 2017; 19: 71\u201380.","DOI":"10.31887\/DCNS.2017.19.1\/rpal"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Liu TW, Chen CM, Chang KH. Biomarker of Neuroinflammation in Parkinson's Disease. International Journal of Molecular Sciences. 2022; 23: 4148.","DOI":"10.3390\/ijms23084148"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Mishra AK, Dixit A. Dopaminergic Axons: Key Recitalists in Parkinson's Disease. Neurochemical Research. 2022; 47: 234\u2013248.","DOI":"10.1007\/s11064-021-03464-1"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"T\u00f6nges L, Frank T, Tatenhorst L, Saal KA, Koch JC, Szego \u00c9M, et al. Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson's disease. Brain : a Journal of Neurology. 2012; 135: 3355\u20133370.","DOI":"10.1093\/brain\/aws254"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Lomenick B, Hao R, Jonai N, Chin RM, Aghajan M, Warburton S, et al. Target identification using drug affinity responsive target stability (DARTS). Proceedings of the National Academy of Sciences of the United States of America. 2009; 106: 21984\u201321989.","DOI":"10.1073\/pnas.0910040106"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Lomenick B, Olsen RW, Huang J. Identification of direct protein targets of small molecules. ACS Chemical Biology. 2011; 6: 34\u201346.","DOI":"10.1021\/cb100294v"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Pai MY, Lomenick B, Hwang H, Schiestl R, McBride W, Loo JA, et al. Drug affinity responsive target stability (DARTS) for small-molecule target identification. Methods in Molecular Biology (Clifton, N.J.). 2015; 1263: 287\u2013298.","DOI":"10.1007\/978-1-4939-2269-7_22"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Chen F, Li C, Cao H, Zhang H, Lu C, Li R, et al. Identification of Adenylate Kinase 5 as a Protein Target of Ginsenosides in Brain Tissues Using Mass Spectrometry-Based Drug Affinity Responsive Target Stability (DARTS) and Cellular Thermal Shift Assay (CETSA) Techniques. Journal of Agricultural and Food Chemistry. 2022; 70: 2741\u20132751.","DOI":"10.1021\/acs.jafc.1c07819"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Derry MM, Somasagara RR, Raina K, Kumar S, Gomez J, Patel M, et al. Target identification of grape seed extract in colorectal cancer using drug affinity responsive target stability (DARTS) technique: role of endoplasmic reticulum stress response proteins. Current Cancer Drug Targets. 2014; 14: 323\u2013336.","DOI":"10.2174\/1568009614666140411101942"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Gcwensa NZ, Russell DL, Cowell RM, Volpicelli-Daley LA. Molecular Mechanisms Underlying Synaptic and Axon Degeneration in Parkinson's Disease. Frontiers in Cellular Neuroscience. 2021; 15: 626128.","DOI":"10.3389\/fncel.2021.626128"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"So YJ, Lee JU, Yang GS, Yang G, Kim SW, Lee JH, et al. The Potentiality of Natural Products and Herbal Medicine as Novel Medications for Parkinson's Disease: A Promising Therapeutic Approach. International Journal of Molecular Sciences. 2024; 25: 1071.","DOI":"10.3390\/ijms25021071"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Luo S, Zhang L, Wu X, Wang J, Li Q, Chen W, et al. Therapeutic potential of neuroprotective plant extracts in Parkinson's disease. Frontiers in Neuroscience. 2026; 20: 1813133.","DOI":"10.3389\/fnins.2026.1813133"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Roni MAH, Jami MABS, Hoque S, Hasibuzzaman MA, Banu KH, Rozina, et al. Clinically proven natural products in aid of treating parkinson's disease: A comprehensive review. Current Medicine. 2024; 3: 6.","DOI":"10.1007\/s44194-024-00033-w"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Freire MAM. Natural compounds in neuroprotection and nervous system regeneration: A narrative review. Regenerative Medicine Reports. 2026; 3: 115-123.","DOI":"10.4103\/REGENMED.REGENMED-D-25-00038"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Zhou M, Sun J, Yu Z, Wu Z, Li W, Liu G, et al. Investigation of Anti-Alzheimer's Mechanisms of Sarsasapogenin Derivatives by Network-Based Combining Structure-Based Methods. Journal of Chemical Information and Modeling. 2023; 63: 2881\u20132894.","DOI":"10.1021\/acs.jcim.3c00018"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Santoro M, Fadda P, Klephan KJ, Hull C, Teismann P, Platt B, et al. Neurochemical, histological, and behavioral profiling of the acute, sub-acute, and chronic MPTP mouse model of Parkinson's disease. Journal of Neurochemistry. 2023; 164: 121\u2013142.","DOI":"10.1111\/jnc.15699"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Luchtman DW, Shao D, Song C. Behavior, neurotransmitters and inflammation in three regimens of the MPTP mouse model of Parkinson's disease. Physiology & Behavior. 2009; 98: 130\u2013138.","DOI":"10.1016\/j.physbeh.2009.04.021"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Brotchie J, Fitzer-Attas C. Mechanisms compensating for dopamine loss in early Parkinson disease. Neurology. 2009; 72: S32\u2013S38.","DOI":"10.1212\/WNL.0b013e318198e0e9"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Takeda A, Tomiyama M, Hanajima R. The Relationship Between Pathophysiology and Neurotransmitters in Parkinson's Disease. Brain and Nerve = Shinkei kenkyu no shinpo. 2021; 73: 829\u2013837.  (In Japanese)","DOI":"10.11477\/mf.1416201843"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Aslan FS, Barut B, Ozturk S, Eyigurbuz T, Akyuz E. Neurotransmitter Dysregulation in Parkinson's Disease: Pathophysiological Insights and Therapeutic Perspectives. ACS Chemical Neuroscience. 2026; 17: 1432\u20131461.","DOI":"10.1021\/acschemneuro.5c00809"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Pajares M, I Rojo A, Manda G, Bosc\u00e1 L, Cuadrado A. Inflammation in Parkinson's Disease: Mechanisms and Therapeutic Implications. Cells. 2020; 9: 1687.","DOI":"10.3390\/cells9071687"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Williams GP, Schonhoff AM, Jurkuvenaite A, Gallups NJ, Standaert DG, Harms AS. CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson's disease. Brain : a Journal of Neurology. 2021; 144: 2047\u20132059.","DOI":"10.1093\/brain\/awab103"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Freire MAM, Rocha GS, Lemos NAM, Lima RR, Bittar S, Jenkins LB, et al. Insights into parkinson's disease pathology focusing on glial response and apoptosis in a classic rat model of dopaminergic degeneration. Neuroglia. 2025; 6: 36.","DOI":"10.3390\/neuroglia6030036"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Tagliaferro P, Burke RE. Retrograde Axonal Degeneration in Parkinson Disease. Journal of Parkinson's Disease. 2016; 6: 1\u201315.","DOI":"10.3233\/JPD-150769"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Ito S, Nagata K. Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone. Seminars in Cell & Developmental Biology. 2017; 62: 142\u2013151.","DOI":"10.1016\/j.semcdb.2016.11.005"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Bentea E, Verbruggen L, Massie A. The Proteasome Inhibition Model of Parkinson's Disease. Journal of Parkinson's Disease. 2017; 7: 31\u201363.","DOI":"10.3233\/JPD-160921"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Sepulveda D, Rojas-Rivera D, Rodr\u00edguez DA, Groenendyk J, K\u00f6hler A, Lebeaupin C, et al. 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