{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:36Z","timestamp":1785437976867,"version":"3.56.0"},"reference-count":70,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","award":["23015"],"award-info":[{"award-number":["23015"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]},{"award":["23015"],"award-info":[{"award-number":["23015"]}],"id":[{"id":"https:\/\/ror.org\/05q60vz69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["86923"],"award-info":[{"award-number":["86923"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"NRF Thutuka","doi-asserted-by":"publisher","award":["TTK230105669155"],"award-info":[{"award-number":["TTK230105669155"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007782","name":"Tshwane University of Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007782","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/037mrss42","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Parkinson\u2019s disease (PD), impacting millions worldwide, leads to motor deficits and various non-motor symptoms. Although there is no cure, treatment primarily involves dopamine replacement therapy, especially L-dopa for motor symptoms, and additional drugs are required to address non-motor effects. This underscores the increasing demand for dual-acting drugs that can effectively target both symptom types in PD. This study explored the potential effects of a standardised Mesembryanthemum tortuosum extract, Zembrin\u00ae, in treating PD, utilising in vivo and in silico models. Zebrafish larvae were subjected to pre-treatment with reserpine, followed by exposure to Zembrin\u00ae, with selegiline and L-dopa as positive controls. The in vivo component of this study monitored locomotion and oxidative stress, while the in silico component identified potential drug targets for the treatment of PD. Reserpine induced hypolocomotion and oxidative stress in zebrafish larvae, and Zembrin\u00ae (12.5 \u00b5g\/mL) effectively enhanced locomotion and reduced oxidative stress. The molecular docking, molecular dynamics simulations, and binding free energy calculations revealed that four mesembrine alkaloids (mesembranol, mesembrenol, mesembrenone, and mesembrine) form stable and energetically favourable complexes with monoamine oxidase B (MAO-B) and dopamine transporter (DAT), which are significant targets for addressing both the motor and non-motor effects of PD.<\/jats:p>","DOI":"10.3390\/molecules31132369","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:43:11Z","timestamp":1783334591000},"page":"2369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Zembrin\u00ae Mitigates Reserpine-Induced Motor Dysfunction and Oxidative Stress in Parkinson\u2019s Disease: In Vivo and In Silico Analyses"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2162-386X","authenticated-orcid":false,"given":"Keagile","family":"Lepule","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxleene","family":"Sandasi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"},{"name":"SAMRC Herbal Drugs Research Unit, Faculty of Science, Tshwane University of Technology, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8713-5001","authenticated-orcid":false,"given":"Elliasu","family":"Salifu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6810-2981","authenticated-orcid":false,"given":"Alvaro","family":"Viljoen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"},{"name":"SAMRC Herbal Drugs Research Unit, Faculty of Science, Tshwane University of Technology, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S1474-4422(17)30299-5","article-title":"Gbd 2015 Neurological Disorders Collaborator Group. Global, Regional, and National Burden of Neurological Disorders During 1990\u20132015: A Systematic Analysis for the Global Burden of Disease Study 2015","volume":"16","author":"Feigin","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e080952","DOI":"10.1136\/bmj-2024-080952","article-title":"Projections for Prevalence of Parkinson\u2019s Disease and Its Driving Factors in 195 Countries and Territories to 2050: Modelling Study of Global Burden of Disease Study 2021","volume":"388","author":"Su","year":"2025","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1212\/WNL.0b013e3181a1d44c","article-title":"The Scientific and Clinical Basis for the Treatment of Parkinson Disease","volume":"72","author":"Olanow","year":"2009","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1212\/CON.0000000000000764","article-title":"Parkinson Disease","volume":"25","author":"Zesiewicz","year":"2019","journal-title":"Contin. Lifelong Learn. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1590\/0004-282X20150029","article-title":"Non-Motor Signs in Parkinson\u2019s Disease: A Review","volume":"73","author":"Munhoz","year":"2015","journal-title":"Arq. Neuropsiquiatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.jagp.2019.03.002","article-title":"The Neuropsychiatry of Parkinson Disease: A Perfect Storm","volume":"27","author":"Weintraub","year":"2019","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yuan, H., Ma, Q., Ye, L., and Piao, G. (2016). The Traditional Medicine and Modern Medicine from Natural Products. Molecules, 21.","DOI":"10.3390\/molecules21050559"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Castellano-Tejedor, C. (2022). Non-Pharmacological Interventions for the Management of Chronic Health Conditions and Non-Communicable Diseases. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19148536"},{"key":"ref_10","first-page":"1251","article-title":"Challenges and Opportunities in Drug Discovery from Plants","volume":"92","author":"Jachak","year":"2007","journal-title":"Curr. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.jep.2011.07.035","article-title":"Pharmacological Actions of the South African Medicinal and Functional Food Plant Sceletium tortuosum and Its Principal Alkaloids","volume":"137","author":"Harvey","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.fct.2014.09.017","article-title":"A Toxicological Safety Assessment of a Standardized Extract of Sceletium tortuosum (Zembrin\u00ae) in Rats","volume":"74","author":"Murbach","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jep.2018.05.010","article-title":"Effect of Zembrin\u00ae and Four of Its Alkaloid Constituents on Electric Excitability of the Rat Hippocampus","volume":"223","author":"Dimpfel","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"114550","DOI":"10.1016\/j.jep.2021.114550","article-title":"An Acute Dose-Ranging Evaluation of the Antidepressant Properties of Sceletium tortuosum (Zembrin\u00ae) Versus Escitalopram in the Flinders Sensitive Line Rat","volume":"284","author":"Gericke","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"117113","DOI":"10.1016\/j.jep.2023.117113","article-title":"Sceletium tortuosum-Derived Mesembrine Significantly Contributes to the Anxiolytic Effect of Zembrin\u00ae, but Its Anti-Depressant Effect May Require Synergy of Multiple Plant Constituents","volume":"319","author":"Gericke","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1089\/acm.2012.0185","article-title":"A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of Extract Sceletium tortuosum (Zembrin) in Healthy Adults","volume":"19","author":"Nell","year":"2013","journal-title":"J. Altern. Complement. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1038\/npp.2013.183","article-title":"Acute Effects of Sceletium tortuosum (Zembrin), a Dual 5-HT Reuptake and PDE4 Inhibitor, in the Human Amygdala and Its Connection to the Hypothalamus","volume":"38","author":"Terburg","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_18","first-page":"31","article-title":"Neuroprotective Effect of Extract-Fractions from Sceletium tortuosum and Their Preliminary Constituents Identification by Uplc-Qtof-Ms with Collision Energy and Massfragment Software","volume":"11","author":"Luo","year":"2021","journal-title":"J. Pharm. Biomed. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Luo, Y., Shan, L., Xu, L., Patnala, S., Kanfer, I., Li, J., Yu, P., and Jun, X. (2022). A Network Pharmacology-Based Approach to Explore the Therapeutic Potential of Sceletium tortuosum in the Treatment of Neurodegenerative Disorders. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0273583"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"120314","DOI":"10.1016\/j.jep.2025.120314","article-title":"Neuroprotective and Neurorestorative Properties of Mesembryanthemum tortuosum in a Parkinson\u2019s Disease Zebrafish Larvae Model","volume":"353","author":"Lepule","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Le\u00e3o, A.H., Meurer, Y.S., da Silva, A.F., Medeiros, A.M., Camp\u00ealo, C.L., Ab\u00edlio, V.C., Engelberth, R.C., Cavalcante, J.S., Iz\u00eddio, G.S., and Ribeiro, A.M. (2017). Spontaneously Hypertensive Rats (Shr) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson\u2019s Disease: Differences in Motor Behaviour, Tyrosine Hydroxylase and A-Synuclein Expression. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00078"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S0278-5846(01)00333-5","article-title":"Evaluation of the Face Validity of Reserpine Administration as an Animal Model of Depression\u2013Parkinson\u2019s Disease Association","volume":"26","author":"Skalisz","year":"2002","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/bpa.12253","article-title":"Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson\u2019s Disease: New Perspectives to a Long-Standing Model","volume":"25","author":"Santos","year":"2015","journal-title":"Brain Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.cbpc.2019.05.008","article-title":"Developmental Neurotoxicity of Reserpine Exposure in Zebrafish Larvae (Danio Rerio)","volume":"223","author":"Wang","year":"2019","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Li, Y., Yin, Q., Wang, B., Shen, T., Luo, W., and Liu, T. (2022). Preclinical reserpine models recapitulating motor and non-motor features of Parkinson\u2019s disease: Roles of epigenetic upregulation of alpha-synuclein and autophagy impairment. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.944376"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00221-026-07316-8","article-title":"Predictive validation of the repeated low-dose reserpine rodent model of parkinsonism","volume":"244","author":"Bioni","year":"2026","journal-title":"Exp. Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.tins.2014.02.011","article-title":"Zebrafish Models for Translational Neuroscience Research: From Tank to Bedside","volume":"37","author":"Stewart","year":"2014","journal-title":"Trends Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ochenkowska, K., Herold, A., and Samarut, \u00c9. (2022). Zebrafish Is a Powerful Tool for Precision Medicine Approaches to Neurological Disorders. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.944693"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.nbd.2010.05.010","article-title":"The Comparative Neuroanatomy and Neurochemistry of Zebrafish CNS Systems of Relevance to Human Neuropsychiatric Diseases","volume":"40","author":"Panula","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.brainresbull.2007.10.043","article-title":"Functional and Developmental Analysis of the Blood\u2013Brain Barrier in Zebrafish","volume":"75","author":"Jeong","year":"2008","journal-title":"Brain Res. Bull."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.tips.2013.12.002","article-title":"Zebrafish as an Emerging Model for Studying Complex Brain Disorders","volume":"35","author":"Kalueff","year":"2014","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115068","DOI":"10.1016\/j.jep.2022.115068","article-title":"Mesembryanthemum tortuosum L. Alkaloids Modify Anxiety-Like Behaviour in a Zebrafish Model","volume":"290","author":"Maphanga","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jep.2016.12.004","article-title":"Mesembrine Alkaloids: Review of Their Occurrence, Chemistry, and Pharmacology","volume":"195","author":"Krstenansky","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.sajb.2012.05.004","article-title":"Validated RP-UHPLC PDA and GC\u2013MS methods for the analysis of psychoactive alkaloids in Sceletium tortuosum","volume":"82","author":"Shikanga","year":"2012","journal-title":"S. Afr. J. Bot."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S287","DOI":"10.1038\/sj.bjp.0706464","article-title":"Monoamine Oxidase: Isoforms and Inhibitors in Parkinson\u2019s Disease and Depressive Illness","volume":"147","author":"Youdim","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.pharmthera.2014.02.010","article-title":"Update on the Pharmacology of Selective Inhibitors of MAO-A and MAO-B: Focus on Modulation of CNS Monoamine Neurotransmitter Release","volume":"143","author":"Finberg","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1124\/pr.110.002642","article-title":"The Physiology, Signaling, and Pharmacology of Dopamine Receptors","volume":"63","author":"Beaulieu","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mori, A., Chen, J.F., Uchida, S., Durlach, C., King, S.M., and Jenner, P. (2022). The Pharmacological Potential of Adenosine A2a Receptor Antagonists for Treating Parkinson\u2019s Disease. Molecules, 27.","DOI":"10.3390\/molecules27072366"},{"key":"ref_39","first-page":"97","article-title":"Istradefylline for Off Episodes in Parkinson\u2019s Disease: A Us Perspective of Common Clinical Scenarios","volume":"12","author":"Isaacson","year":"2022","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nsb732","article-title":"Structure of Human Monoamine Oxidase B, a Drug Target for the Treatment of Neurological Disorders","volume":"9","author":"Binda","year":"2002","journal-title":"Nat. Struct. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Osmaniye, D., Kurban, B., Sa\u011flik, B.N., Levent, S., \u00d6zkay, Y., and Kaplancikli, Z.A. (2021). Novel Thiosemicarbazone Derivatives: In vitro and in silico Evaluation as Potential MAO-B Inhibitors. Molecules, 26.","DOI":"10.3390\/molecules26216640"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/nature14431","article-title":"Neurotransmitter and Psychostimulant Recognition by the Dopamine Transporter","volume":"521","author":"Wang","year":"2015","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chia, S.J., Eng-King, T., and Yin-Xia, C. (2020). Historical Perspective: Models of Parkinson\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072464"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3060","DOI":"10.1038\/s41598-017-02981-w","article-title":"Storage of Neural Histamine and Histaminergic Neurotransmission Is VMAT2 Dependent in the Zebrafish","volume":"7","author":"Puttonen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110874","DOI":"10.1016\/j.pnpbp.2023.110874","article-title":"Transcriptome Profile of Reserpine-Induced Locomotor Behavioral Changes in Zebrafish (Danio Rerio)","volume":"129","author":"Luo","year":"2024","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1089\/zeb.2013.0950","article-title":"Effects of 6-hydroxydopamine exposure on motor activity and biochemical expression in zebrafish (Danio rerio) larvae","volume":"11","author":"Feng","year":"2014","journal-title":"Zebrafish"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sun, F., Xia, L., Wang, B., Liu, Y., Cui, X., Kang, H., Stoika, R., Liu, K., and Jin, M. (2025). Reserpine Causes Neuroendocrine Toxicity, Inducing Impairments in Cognition Via Disturbing Hypothalamic\u2013Pituitary\u2013Thyroid Axis in Zebrafish. NeuroSci, 6.","DOI":"10.3390\/neurosci6020028"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.brainres.2013.06.033","article-title":"Behavioral effects of bidirectional modulators of brain monoamines reserpine and d-amphetamine in zebrafish","volume":"21","author":"Kyzar","year":"2013","journal-title":"Brain Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jep.2015.11.034","article-title":"High-Mesembrine Sceletium Extract (Trimesemine\u2122) Is a Monoamine Releasing Agent, Rather Than Only a Selective Serotonin Reuptake Inhibitor","volume":"117","author":"Coetzee","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1007\/s00213-020-05642-5","article-title":"Screening Selected Medicinal Plants for Potential Anxiolytic Activity Using an in Vivo Zebrafish Model","volume":"237","author":"Maphanga","year":"2020","journal-title":"Psychopharmacology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.tins.2008.02.010","article-title":"Altered Vesicular Dopamine Storage in Parkinson\u2019s Disease: A Premature Demise","volume":"31","author":"Caudle","year":"2008","journal-title":"Trends Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.bbr.2012.03.008","article-title":"Repeated Treatment with a Low Dose of Reserpine as a Progressive Model of Parkinson\u2019s Disease","volume":"231","author":"Fernandes","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.sajb.2016.06.009","article-title":"Sceletium tortuosum Demonstrates in vitro anti-Hiv and Free Radical Scavenging Activity","volume":"106","author":"Kapewangolo","year":"2016","journal-title":"S. Afr. J. Bot."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s13105-018-0620-6","article-title":"Sceletium tortuosum May Delay Chronic Disease Progression Via Alkaloid-Dependent Antioxidant or Anti-Inflammatory Action","volume":"74","author":"Bennett","year":"2018","journal-title":"J. Physiol. Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.jep.2008.07.043","article-title":"Sceletium\u2014A Review Update","volume":"119","author":"Gericke","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/ana.24859","article-title":"Serotonin Transporter in Parkinson\u2019s Disease: A Meta-Analysis of Positron Emission Tomography Studies","volume":"81","author":"Pagano","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1134\/S181971242301004X","article-title":"The Role of the Serotonergic System of the Brain in the Pathogenesis of Parkinson\u2019s Disease","volume":"17","author":"Ahsas","year":"2023","journal-title":"Neurochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"228","DOI":"10.2165\/00002512-199101030-00006","article-title":"Selegiline: A Review of Its Pharmacology, Symptomatic Benefits and Protective Potential in Parkinson\u2019s Disease","volume":"1","author":"Chrisp","year":"1991","journal-title":"Drugs Aging"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00894-024-05889-1","article-title":"Probing the Inhibition of MAO-B by Chalcones: An Integrated Approach Combining Molecular Docking, Adme Analysis, MD Simulation, and Mm-Pbsa Calculations","volume":"30","author":"Jose","year":"2024","journal-title":"J. Mol. Model."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.neuint.2018.08.008","article-title":"Identification of the Benztropine Analog [125i] Ga Ii 34 Binding Site on the Human Dopamine Transporter","volume":"123","author":"Tomlinson","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.sajb.2018.10.011","article-title":"To Ferment or Not to Ferment Sceletium Tortuosum\u2013Do Our Ancestors Hold the Answer?","volume":"122","author":"Chen","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_62","unstructured":"Westerfield, M. (2007). The Zebrafish Book; A Guide for the Laboratory Use of Zebrafish (Danio Rerio), University of Oregon Press. [5th ed.]."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.chemosphere.2018.01.045","article-title":"Novel Procedures for Whole Organism Detection and Quantification of Fluorescence as a Measurement for Oxidative Stress in Zebrafish (Danio rerio) Larvae","volume":"197","author":"Lackmann","year":"2018","journal-title":"Chemosphere"},{"key":"ref_64","unstructured":"Case, D.A., Ben-Shalom, I.-Y., Brozell, S.R., Cerutti, D.S., Cheatham, T.E., Cruzeiro, V.W.D., Darden, T.A., Duke, R.E., Ghoreishi, D., and Gilson, M.K. (2018). Amber 2018, University of California."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5882","DOI":"10.1021\/acs.jpcb.5b00689","article-title":"The General Amber Force Field (Gaff) Can Accurately Predict Thermodynamic and Transport Properties of Many Ionic Liquids","volume":"119","author":"Sprenger","year":"2015","journal-title":"J. Phys. Chem. B"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"Improving the Accuracy of Protein Side Chain and Backbone Parameters from Ff99sb","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_67","unstructured":"Nikitin, S. (2014). Leap Gradient Algorithm. arXiv."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.jcp.2006.05.032","article-title":"P-Shake: A Quadratically Convergent Shake in O (N2)","volume":"220","author":"Gonnet","year":"2007","journal-title":"J. Comput. Phys."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"Software for Processing and Analysis of Molecular Dynamics Trajectory Data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1021\/ci4002475","article-title":"MMGBSA as a Tool to Understand the Binding Affinities of Filamin\u2013Peptide Interactions","volume":"53","author":"Ylilauri","year":"2013","journal-title":"J. Chem. Inf. Model."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/13\/2369\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:38:16Z","timestamp":1783399096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/13\/2369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,5]]},"references-count":70,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["molecules31132369"],"URL":"https:\/\/doi.org\/10.3390\/molecules31132369","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,5]]}}}