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One of the main mechanisms underlying this process involves the persistent activation of glial cells. Persistent activation of glial cells induces proinflammatory transcription factors and the release of cytokines, chemokines, and reactive oxygen species that exacerbate cellular dysfunction. This neurotoxic environment promotes neuronal death, while the products of cellular damage feed back into glial activation, establishing a self-sustaining pathogenic cycle that drives neurodegeneration. Alkaloids present in Amaryllidaceae plants support the use of this resource in folk medicine, displaying potent effects as acetylcholinesterase inhibitors and allosteric modulators of nicotinic receptors (nAChR). In this study, a murine microglial cell (IMG) model of LPS-induced inflammation was used to evaluate the involvement of \u03b17 and \u03b14\u03b22 nAChRs in glioprotection and neuroprotection of SH-SY5Y cells against 6-hydroxydopamine (OHDA). GC-MS analysis revealed differences in the alkaloid profile between in vitro cultures with fructose and wild-type Rhodophiala pratensis. Homolycorine-type, norbelladine-type and crinine-type alkaloids produced in vitro reduced LPS-induced inflammation (5 \u00b5g\/mL), possibly via \u03b17 and \u03b14\u03b22 nAChRs, and showed a protective effect against OHDA-induced oxidative stress (1\u20133 \u00b5g\/mL) and inhibited AChE and BuChE (24\u201378 \u00b5g\/mL).<\/jats:p>","DOI":"10.3390\/plants15081186","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:29:29Z","timestamp":1776065369000},"page":"1186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alkaloids from In Vitro Cultured Rhodophiala pratensis Display Neuroprotective Effects in Murine Microglial Cell Models of Inflammation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9058-991X","authenticated-orcid":false,"given":"Diana","family":"Correa-Otero","sequence":"first","affiliation":[{"name":"Facultad de Ciencias, Universidad San Sebasti\u00e1n, Concepci\u00f3n 4030000, Chile"},{"name":"Laboratorio de S\u00edntesis y Biotransformaci\u00f3n de Productos Naturales, Departamento Ciencias B\u00e1sicas, Universidad del Bio-Bio, Chill\u00e1n 4081112, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandis","family":"Fiallos","sequence":"additional","affiliation":[{"name":"Laboratorio de S\u00edntesis y Biotransformaci\u00f3n de Productos Naturales, Departamento Ciencias B\u00e1sicas, Universidad del Bio-Bio, Chill\u00e1n 4081112, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela","family":"G\u00f3mez-Mediavilla","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Instituto Te\u00f3filo Hernando (ITH), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-8788","authenticated-orcid":false,"given":"Manuela G.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Instituto Te\u00f3filo Hernando (ITH), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0896-5819","authenticated-orcid":false,"given":"Carlota","family":"Siguero-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Instituto Te\u00f3filo Hernando (ITH), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5077-474X","authenticated-orcid":false,"given":"Luis","family":"Bustamante","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lisis Instrumental, Facultad de Farmacia, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7473-8823","authenticated-orcid":false,"given":"Julio","family":"Alarc\u00f3n-Enos","sequence":"additional","affiliation":[{"name":"Laboratorio de S\u00edntesis y Biotransformaci\u00f3n de Productos Naturales, Departamento Ciencias B\u00e1sicas, Universidad del Bio-Bio, Chill\u00e1n 4081112, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5437-9210","authenticated-orcid":false,"given":"Edgar","family":"Pastene-Navarrete","sequence":"additional","affiliation":[{"name":"Laboratorio de S\u00edntesis y Biotransformaci\u00f3n de Productos Naturales, Departamento Ciencias B\u00e1sicas, Universidad del Bio-Bio, Chill\u00e1n 4081112, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.3892\/mmr.2016.4948","article-title":"Role of Neuroinflammation in Neurodegenerative Diseases (Review)","volume":"13","author":"Chen","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2023). Alzheimer\u2019s Disease Facts and Figures. Alzehimer\u2019s Dement., 19, 1598\u20131695.","DOI":"10.1002\/alz.13016"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Giri, P.M., Banerjee, A., Ghosal, A., and Layek, B. (2024). Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073995"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","article-title":"Inflammation as a Central Mechanism in Alzheimer\u2019s Disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s00018-023-04775-y","article-title":"Aging Microglia","volume":"80","author":"Antignano","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","first-page":"302","article-title":"El Microglia in Health and Disease. Cold Spring Harb","volume":"8","author":"Ransohoff","year":"2016","journal-title":"Perspect. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/jnr.10253","article-title":"Cytokines, Chemokines, and Cytokine Receptors in Human Microglia","volume":"69","author":"Lee","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"De Marchi, F., Munitic, I., Vidatic, L., Papic, E., Racki, V., Nimac, J., Jurak, I., Novotni, G., Rogelj, B., and Vuletic, V. (2023). Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders. Biomedicines, 11.","DOI":"10.20944\/preprints202309.0808.v1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41593-018-0100-x","article-title":"Single-Cell Mass Cytometry Reveals Distinct Populations of Brain Myeloid Cells in Mouse Neuroinflammation and Neurodegeneration Models","volume":"21","author":"Ajami","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.bcp.2015.07.032","article-title":"Anti-Inflammatory Role of Microglial Alpha7 NAChRs and Its Role in Neuroprotection","volume":"97","author":"Egea","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Le, W., Wu, J., and Tang, Y. (2016). Protective Microglia and Their Regulation in Parkinson\u2019s Disease. Front. Mol. Neurosci., 9.","DOI":"10.3389\/fnmol.2016.00089"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.bbi.2005.03.015","article-title":"The Cholinergic Anti-Inflammatory Pathway","volume":"19","author":"Pavlov","year":"2005","journal-title":"Brain. Behav. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature01339","article-title":"Nicotinic Acetylcholine Receptor A7 Subunit Is an Essential Regulator of Inflammatio","volume":"421","author":"Wang","year":"2003","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/j.1365-2796.2009.02098.x","article-title":"Cholinergic Control of Inflammation","volume":"265","author":"Tracey","year":"2009","journal-title":"J. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1021\/jm040219e","article-title":"Neuronal Nicotinic Acetylcholine Receptors: Structural Revelations, Target Identifications, and Therapeutic Inspirations","volume":"48","author":"Jensen","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1093\/brain\/awy099","article-title":"Cognitive Correlates of A4\u03b22 Nicotinic Acetylcholine Receptors in Mild Alzheimer\u2019s Dementia","volume":"141","author":"Sabri","year":"2018","journal-title":"Brain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.bcp.2011.05.001","article-title":"Positive Allosteric Modulators as an Approach to Nicotinic Acetylcholine Receptor-Targeted Therapeutics: Advantages and Limitations","volume":"82","author":"Williams","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Alzarea, S., Khan, A., Ronan, P.J., Lutfy, K., and Rahman, S. (2024). The \u03b1-7 Nicotinic Receptor Positive Allosteric Modulator Alleviates Lipopolysaccharide Induced Depressive-like Behavior by Regulating Microglial Function, Trophic Factor, and Chloride Transporters in Mice. Brain Sci., 14.","DOI":"10.3390\/brainsci14030290"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mitra, S., Khatri, S.N., Maulik, M., Bult-Ito, A., and Schulte, M. (2020). Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144918"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mohamed, T.S., Jayakar, S.S., and Hamouda, A.K. (2015). Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation. Front. Mol. Neurosci., 8.","DOI":"10.3389\/fnmol.2015.00071"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"137654","DOI":"10.1016\/j.neulet.2024.137654","article-title":"Effects of A7 Nicotinic Acetylcholine Receptor Agonist against \u03b1-Synuclein-Induced Neurotoxicity","volume":"823","author":"Takizawa","year":"2024","journal-title":"Neurosci. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/toxsci\/kfr163","article-title":"Neurotoxicity Induced by Okadaic Acid in the Human Neuroblastoma SH-SY5Y Line Can Be Differentially Prevented by A7 and \u03922* Nicotinic Stimulation","volume":"123","author":"Romero","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.lfs.2014.12.011","article-title":"Neuroprotective Activity and Acetylcholinesterase Inhibition of Five Amaryllidaceae Species: A Comparative Study","volume":"122","author":"Cortes","year":"2015","journal-title":"Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"110665","DOI":"10.1016\/j.fct.2019.110665","article-title":"Neuroprotective Activity of Isoquinoline Alkaloids from of Chilean Amaryllidaceae Plants against Oxidative Stress-Induced Cytotoxicity on Human Neuroblastoma SH-SY5Y Cells and Mouse Hippocampal Slice Culture","volume":"132","author":"Bustamante","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s11064-025-04354-6","article-title":"Alkaloids from Caliphruria subedentata (Amaryllidaceae) as Regulators of AChE, BuChE, NMDA and GSK3 Activity: An In Vitro and In Silico Approach for Mimicking Alzheimer\u2019s Disease","volume":"50","author":"Palomino","year":"2025","journal-title":"Neurochem. Res."},{"key":"ref_26","unstructured":"Preedy, V.R. (2020). Chapter 13\u2014Amaryllidaceae Alkaloids and Neuronal Cell Protection. Pathology, Academic Press."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.neuro.2016.10.013","article-title":"Galantamine Decreases Genotoxicity and Cell Death Induced by \u03b2-Amyloid Peptide in SH-SY5Y Cell Line","volume":"57","author":"Castillo","year":"2016","journal-title":"Neurotoxicology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0028-3908(03)00317-4","article-title":"Galantamine Prevents Apoptosis Induced by \u03b2-Amyloid and Thapsigargin: Involvement of Nicotinic Acetylcholine Receptors","volume":"46","author":"Arias","year":"2004","journal-title":"Neuropharmacology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1124\/jpet.105.090365","article-title":"Unequal Neuroprotection Afforded by the Acetylcholinesterase Inhibitors Galantamine, Donepezil, and Rivastigmine in SHSY5Y Neuroblastoma Cells: Role of Nicotinic Receptors","volume":"315","author":"Arias","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.neuropharm.2011.10.022","article-title":"Galantamine Elicits Neuroprotection by Inhibiting INOS, NADPH Oxidase and ROS in Hippocampal Slices Stressed with Anoxia\/Reoxygenation","volume":"62","author":"Egea","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ma, C., Hong, F., and Yang, S. (2022). Amyloidosis in Alzheimer\u2019s Disease: Pathogeny, Etiology, and Related Therapeutic Directions. Molecules, 27.","DOI":"10.3390\/molecules27041210"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S0006-2952(02)01514-9","article-title":"\u03b2-Amyloid Aggregation Induced by Human Acetylcholinesterase: Inhibition Studies","volume":"65","author":"Bartolini","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e202300461","DOI":"10.1002\/slct.202300461","article-title":"Enhancing the Therapeutic Effect in Alzheimer\u2019s Disease Drugs: The Role of Polypharmacology and Cholinesterase Inhibitors","volume":"8","author":"Martins","year":"2023","journal-title":"ChemistrySelect"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8471","DOI":"10.1038\/s41598-019-44746-7","article-title":"Amaryllidaceae Alkaloids: Identification and Partial Characterization of Montanine Production in Rhodophiala Bifida Plant","volume":"9","author":"Reis","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e8688","DOI":"10.7717\/peerj.8688","article-title":"Carbohydrates Stimulated Amaryllidaceae Alkaloids Biosynthesis in Leucojum aestivum L. Plants Cultured in RITA\u00ae Bioreactor","volume":"2020","author":"Ptak","year":"2020","journal-title":"PeerJ"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s11240-022-02368-4","article-title":"Effect of Plant Growth Regulators on Alkaloid the Production in Cell Cultures of Chilean Amaryllidaceae: Rhodophiala pratensis, Rhodophiala splendens, Rhodophiala advena, and Rhodolirium speciosum","volume":"151","author":"Correa","year":"2022","journal-title":"Plant Cell Tissue Organ Cult."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1007\/s11033-012-2299-z","article-title":"Review: Role of Carbon Sources for In Vitro Plant Growth and Development","volume":"40","author":"Yaseen","year":"2013","journal-title":"Mol. Biol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1105\/tpc.010455","article-title":"Sugar Sensing and Signaling in Plants","volume":"14","author":"Rolland","year":"2002","journal-title":"Plant Cell"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Huang, Z., Gao, C., Xu, Y., Liu, J., Kang, J., Ren, Z., Cui, Q., Li, D., Ma, S., and Xia, Y. (2024). Identification and Expression Analysis of Putative Sugar Transporter Gene Family during Bulb Formation in Lilies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063483"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"24315","DOI":"10.1038\/s41598-021-03845-0","article-title":"The Impact of Carbon Source on Cell Growth and the Production of Bioactive Compounds in Cell Suspensions of Hancornia speciosa Gomes","volume":"11","author":"Dantas","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Xu, J., Li, Q., Yang, L., Li, X., Wang, Z., and Zhang, Y. (2020). Changes in Carbohydrate Metabolism and Endogenous Hormone Regulation during Bulblet Initiation and Development in Lycoris radiata. BMC Plant Biol., 20.","DOI":"10.1186\/s12870-020-02394-4"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Fathi, M., Vakili, K., Yaghoobpoor, S., Qadirifard, M.S., Kosari, M., Naghsh, N., Asgaritaei, A., Klegeris, A., Dehghani, M., and Bahrami, A. (2022). Pre-Clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson\u2019s Disease: A Systematic Review. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.855776"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tallini, L.R., Bastida, J., Cortes, N., Osorio, E.H., Theoduloz, C., and Schmeda-Hirschmann, G. (2018). Cholinesterase Inhibition Activity, Alkaloid Profiling and Molecular Docking of Chilean Rhodophiala (Amaryllidaceae). Molecules, 23.","DOI":"10.3390\/molecules23071532"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.molmed.2023.12.002","article-title":"Omaveloxolone: A Groundbreaking Milestone as the First FDA-Approved Drug for Friedreich Ataxia","volume":"30","author":"Pilotto","year":"2024","journal-title":"Trends Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.bbrc.2004.10.132","article-title":"Galantamine Modulates Nicotinic Receptor and Blocks A\u03b2-Enhanced Glutamate Toxicity","volume":"325","author":"Kihara","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Frost, E.D., Shi, S.X., Byroju, V.V., Pitton Rissardo, J., Donlon, J., Vigilante, N., Murray, B.P., Walker, I.M., McGarry, A., and Ferraro, T.N. (2024). Galantamine-Memantine Combination in the Treatment of Parkinson\u2019s Disease Dementia. Brain Sci., 14.","DOI":"10.3390\/brainsci14121163"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Al Mamun, A., Pidan\u00fd, F., Hulcov\u00e1, D., Ma\u0159\u00edkov\u00e1, J., Ku\u010dera, T., Schmidt, M., Catapano, M.C., Hrabinov\u00e1, M., Jun, D., and M\u00fa\u010dkov\u00e1, L. (2021). Amaryllidaceae Alkaloids of Norbelladine-type as Inspiration for Development of Highly Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Activity Evaluation and Docking Studies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158308"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/jxb\/erae187","article-title":"Navigating Amaryllidaceae Alkaloids: Bridging Gaps and Charting Biosynthetic Territories\u2014A Comprehensive Review","volume":"76","author":"Liyanage","year":"2024","journal-title":"J. Exp. Bot."},{"key":"ref_49","unstructured":"Bastida, J., Berkov, S., Torras, L., Pigni, N., De Andradre, J.P., Mart\u00ednez, V., Codina, C., and Viladomat, F. (2011). Chemical and Biological Aspects of Amaryllidaceae Alkaloids. Recent Advances in Pharmaceutical Sciences, Transworld Research Network."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/bs.alkal.2019.10.002","article-title":"Chemodiversity, Chemotaxonomy and Chemoecology of Amaryllidaceae Alkaloids","volume":"83","author":"Berkov","year":"2020","journal-title":"Alkaloids Chem. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6649","DOI":"10.1007\/s00253-021-11539-w","article-title":"Production of Bioactive Plant Secondary Metabolites through In Vitro Technologies\u2014Status and Outlook","volume":"105","author":"Wawrosch","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.bjp.2019.02.001","article-title":"Influence of In Vitro Micropropagation on Lycorine Biosynthesis and Anticholinesterase Activity in Hippeastrum goianum","volume":"29","author":"Simeoni","year":"2019","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tallini, L.R., De Andrade, J.P., Kaiser, M., Viladomat, F., Nair, J.J., Zuanazzi, J.A.S., and Bastida, J. (2017). Alkaloid Constituents of the Amaryllidaceae Plant Amaryllis belladonna L. Molecules, 22.","DOI":"10.3390\/molecules22091437"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Koirala, M., Karimzadegan, V., Liyanage, N.S., M\u00e9rindol, N., and Desgagn\u00e9-Penix, I. (2022). Biotechnological Approaches to Optimize the Production of Amaryllidaceae Alkaloids. Biomolecules, 12.","DOI":"10.3390\/biom12070893"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.sajb.2021.04.016","article-title":"Enhancement of Alkaloid Content (Galantamine and Lycorine) and Antioxidant Activities (Enzymatic and Non-Enzymatic) Unders Salt Stress in Summer Snowflake (Leucojum aestivum L.)","volume":"140","author":"Ates","year":"2021","journal-title":"S. Afr. J. Bot."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Emamverdian, A., Ding, Y., Mokhberdoran, F., Ramakrishnan, M., Ahmad, Z., and Xie, Y. (2021). Different Physiological and Biochemical Responses of Bamboo to the Addition of TiO2 Nps under Heavy Metal Toxicity. Forests, 12.","DOI":"10.3390\/f12060759"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Emamverdian, A., Ding, Y., Barker, J., Liu, G., Li, Y., and Mokhberdoran, F. (2023). Sodium Nitroprusside Improves Bamboo Resistance under Mn and Cr Toxicity with Stimulation of Antioxidants Activity, Relative Water Content, and Metal Translocation and Accumulation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031942"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11240-022-02229-0","article-title":"Harnessing Plant Biotechnology-Based Strategies for In Vitro Galantamine (GAL) Biosynthesis: A Potent Drug against Alzheimer\u2019s Disease","volume":"149","author":"Kaur","year":"2022","journal-title":"Plant Cell Tissue Organ Cult."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"102670","DOI":"10.1016\/j.bcab.2023.102670","article-title":"Influence of Plant Growth Regulators on In Vitro Biomass Production and Biosynthesis of Cytotoxic Amaryllidaceae Alkaloids in Caliphuria Tenera Baker","volume":"50","author":"Leiva","year":"2023","journal-title":"Biocatal. Agric. Biotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Girard, M.P., Karimzadegan, V., H\u00e9neault, M., Cloutier, F., B\u00e9rub\u00e9, G., Berthoux, L., M\u00e9rindol, N., and Desgagn\u00e9-Penix, I. (2022). Chemical Synthesis and Biological Activities of Amaryllidaceae Alkaloid Norbelladine Derivatives and Precursors. Molecules, 27.","DOI":"10.3390\/molecules27175621"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5381","DOI":"10.1016\/j.bmcl.2014.10.051","article-title":"Synthesis and Characterization of Norbelladine, a Precursor of Amaryllidaceae Alkaloid, as an Anti-Inflammatory\/Anti-COX Compound","volume":"24","author":"Park","year":"2014","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"40180","DOI":"10.1074\/jbc.M110.142356","article-title":"Galantamine-Induced Amyloid-\u03b2 Clearance Mediated via Stimulation of Microglial Nicotinic Acetylcholine Receptors","volume":"285","author":"Takata","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1021\/np030529k","article-title":"New Crinine-Type Alkaloids with Inhibitory Effect on Induction of Inducible Nitric Oxide Synthase from Crinum Yemense","volume":"67","author":"Morikawa","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"153540","DOI":"10.1016\/j.phymed.2021.153540","article-title":"Narciclasine Inhibits LPS-Induced Neuroinflammation by Modulating the Akt\/IKK\/NF-\u039aB and JNK Signaling Pathways","volume":"85","author":"Zhao","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"35352","DOI":"10.1007\/s11356-022-24292-y","article-title":"Lipopolysaccharide Induces Inflammatory Microglial Activation through CD147-Mediated Matrix Metalloproteinase Expression","volume":"30","author":"Yao","year":"2023","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6547","DOI":"10.1038\/s41598-023-32798-9","article-title":"LPS Induces Microglial Activation and GABAergic Synaptic Deficits in the Hippocampus Accompanied by Prolonged Cognitive Impairment","volume":"13","author":"Jung","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Qin, Y.-H., Luo, Y.-B., Wang, H.-J., Tian, Y.-S., Chen, H., and Hou, H.-W. (2023). Regulation of LPS-Induced Inammatory Responses in HMC3 Microglia by Nicotine and Its Neuroprotective Effects. Res. Sq., 1\u201322.","DOI":"10.21203\/rs.3.rs-2966552\/v1"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Jordan, P., Costa, A., Specker, E., Popp, O., Volkamer, A., Piske, R., Obrusnik, T., Kleissle, S., Stuke, K., and Id, A.R. (2023). Small Molecule Inhibiting Microglial Nitric Oxide Release Could Become a Potential Treatment for Neuroinflammation. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0278325"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1177\/1535370221997052","article-title":"Nitric Oxide Modulation in Neuroinflammation and the Role of Mesenchymal Stem Cells","volume":"246","author":"Liy","year":"2021","journal-title":"Exp. Biol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.neuron.2011.07.001","article-title":"Nitration of Tyrosine 10 Critically Enhances Amyloid b Aggregation and Plaque Formation","volume":"71","author":"Kummer","year":"2011","journal-title":"Neuron"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.lfs.2016.06.019","article-title":"Inducible Nitric Oxide Inhibitor Aminoguanidine, Ameliorates Deleterious Effects of Lipopolysaccharide on Memory and Long Term Potentiation in Rat","volume":"158","author":"Anaeigoudari","year":"2016","journal-title":"Life Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/med.21599","article-title":"Inducible Nitric Oxide Synthase: Regulation, Structure, and Inhibition","volume":"40","author":"Cinelli","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e12455","DOI":"10.1002\/jev2.12455","article-title":"Microglial Activation Induces Nitric Oxide Signalling and Alters Protein S-Nitrosylation Patterns in Extracellular Vesicles","volume":"13","author":"Vassileff","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1084\/jem.20051529","article-title":"Protection from Alzheimer\u2019s-like Disease in the Mouse by Genetic Ablation of Inducible Nitric Oxide Synthase","volume":"202","author":"Nathan","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"20","DOI":"10.31083\/j.jin2201020","article-title":"SH-SY5Y Cell Line In Vitro Models for Parkinson Disease Research-Old Practice for New Trends","volume":"22","author":"Ioghen","year":"2023","journal-title":"J. Integr. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1080\/1028415X.2020.1840035","article-title":"Neuroprotective Effects of Natural Compounds on Neurotoxin-Induced Oxidative Stress and Cell Apoptosis","volume":"25","author":"Chen","year":"2022","journal-title":"Nutr. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"18534","DOI":"10.1038\/s41598-023-45318-6","article-title":"Neuroprotective Effects of Polyacrylic Acid (PAA) Conjugated Cerium Oxide against Hydrogen Peroxide- and 6-OHDA-Induced SH-SY5Y Cell Damage","volume":"13","author":"Meenambal","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.pneurobio.2015.10.004","article-title":"Novel Tactics for Neuroprotection in Parkinson\u2019s Disease: Role of Antibiotics, Polyphenols and Neuropeptides","volume":"155","author":"Reglodi","year":"2015","journal-title":"Prog. Neurobiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s12272-013-0188-1","article-title":"Four New Compounds from the Bulbs of Lycoris Aurea with Neuroprotective Effects against CoCl2 and H2O2-Induced SH-SY5Y Cell Injuries","volume":"37","author":"Jin","year":"2014","journal-title":"Arch. Pharm. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000051227","article-title":"Allosteric Modulation of Nicotinic Receptors as a Treatment Strategy for Alzheimer\u2019s Disease","volume":"11","author":"Maelicke","year":"2000","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.bbr.2016.07.023","article-title":"The Combination of Memantine and Galantamine Improves Cognition in Rats: The Synergistic Role of the A7 Nicotinic Acetylcholine and NMDA Receptors","volume":"313","author":"Nikiforuk","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Omoruyi, S.I., Ibrakaw, A.S., Ekpo, O.E., Boatwright, J.S., Cupido, C.N., and Hussein, A.A. (2021). Neuroprotective Activities of Crossyne Flava Bulbs and Amaryllidaceae Alkaloids: Implications for Parkinson\u2019s Disease. Molecules, 26.","DOI":"10.3390\/molecules26133990"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1055\/a-2369-8104","article-title":"Anti-Inflammatory Principles of the Plant Family Amaryllidaceae","volume":"90","author":"Nair","year":"2024","journal-title":"Planta Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1006\/nbdi.2001.0462","article-title":"Widely Spread Butyrylcholinesterase Can Hydrolyze Acetylcholine in the Normal and Alzheimer Brain","volume":"9","author":"Mesulam","year":"2002","journal-title":"Neurobiol. Dis."},{"key":"ref_85","first-page":"12r01412","article-title":"A Review of Butyrylcholinesterase as a Therapeutic Target in the Treatment of Alzheimer\u2019s Disease","volume":"15","author":"Nordberg","year":"2013","journal-title":"Prim. Care Companion CNS Disord."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/j.1399-3054.1962.tb08052.x","article-title":"A Revised Medium for Rapid Growth and Bio Assays with Tobacco Tissue Cultures","volume":"15","author":"Murashige","year":"1962","journal-title":"Physiol. Plant."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jpba.2014.09.022","article-title":"Alkaloid Metabolite Profiles by GC\/MS and Acetylcholinesterase Inhibitory Activities with Binding-Mode Predictions of Five Amaryllidaceae Plants","volume":"102","author":"Cortes","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Correa, D.I., Pastene-Navarrete, E., Bustamante, L., Baeza, M., and Alarc\u00f3n-Enos, J. (2020). Isolation of Three Lycorine Type Alkaloids from Rhodolirium speciosum (Herb.) Ravenna Using PH-Zone-Refinement Centrifugal Partition Chromatography and Their Acetylcholinesterase Inhibitory Activities. Metabolites, 10.","DOI":"10.3390\/metabo10080309"},{"key":"ref_89","first-page":"483","article-title":"Structure Activity Studies on the Crinane Alkaloid Apoptosis-Inducing Pharmacophore","volume":"4","author":"McNulty","year":"2009","journal-title":"Nat. Prod. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.phytochem.2014.03.007","article-title":"Crinine-Type Alkaloids from Hippeastrum Aulicum and H. Calyptratum","volume":"103","author":"Guo","year":"2014","journal-title":"Phytochemistry"},{"key":"ref_91","first-page":"46","article-title":"In Vitro Micropropagation and Alkaloids Analysis by GC\u2013MS of Chilean Amaryllidaceae Plants: Rhodophiala pratensis","volume":"31","author":"Bustamante","year":"2019","journal-title":"Phytochem. Anal."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.1007\/s00210-023-02914-7","article-title":"Carvedilol Attenuates Inflammatory Reactions of Lipopolysaccharide-Stimulated BV2 Cells and Modulates M1\/M2 Polarization of Microglia via Regulating NLRP3, Notch, and PPAR-\u03b3 Signaling Pathways","volume":"397","author":"Amirshahrokhi","year":"2024","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1006\/niox.1997.0116","article-title":"Improved Methods to Measure End Products of Nitric Oxide in Biological Fluids: Nitrite, Nitrate, and S-Nitrosothiols","volume":"1","author":"Marzinzig","year":"1997","journal-title":"Nitric Oxide"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/8\/1186\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:29:38Z","timestamp":1776068978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/8\/1186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,12]]},"references-count":95,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["plants15081186"],"URL":"https:\/\/doi.org\/10.3390\/plants15081186","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,12]]}}}