{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:00:37Z","timestamp":1785427237785,"version":"3.56.0"},"reference-count":170,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008108","name":"Taipei Tzu Chi Hospital","doi-asserted-by":"crossref","award":["TCRD\u2013TPE\u2013111\u201328 (1\/3)\u2013(3\/3)"],"award-info":[{"award-number":["TCRD\u2013TPE\u2013111\u201328 (1\/3)\u2013(3\/3)"]}],"id":[{"id":"10.13039\/501100008108","id-type":"DOI","asserted-by":"crossref"}]},{"award":["TCRD\u2013TPE\u2013111\u201328 (1\/3)\u2013(3\/3)"],"award-info":[{"award-number":["TCRD\u2013TPE\u2013111\u201328 (1\/3)\u2013(3\/3)"]}],"id":[{"id":"https:\/\/ror.org\/00q017g63","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Neuroinflammation plays an essential role in the pathogenesis of several associated brain diseases, including neurodegenerative disorders (Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), multiple sclerosis (MS)), and traumatic brain injury (TBI). In these diseases, persistent microglial and astrocyte aggregates, elevated proinflammatory cytokines, and oxidative stress drive neuronal injury and cognitive disability. Rho GTPases, in particular the Rho family members Ras homolog family member A (RhoA), Ras-related C3 botulinum toxin substrate 1 (Rac1), and cell division control protein 42 homolog (CDC42), regulate neuroinflammation, cytoskeletal dynamics, immune responses, and the maintenance of BBB integrity. These proteins are involved in many neuropathological diseases due to dysregulation, making them interesting therapeutic targets. Bioactives used in herbal care have attracted interest for their ability to influence neuroinflammation and even their anti-neurodegenerative activity. Studies show that flavonoids, alkaloids, polyphenols, and other botanical compounds alter Rho GTPase activity, which, in turn, leads to decreased inflammation. This review critically summarizes current evidence regarding phytochemical regulation of Rho GTPase signaling in neurodegenerative disorders such as Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD), with particular emphasis on the underlying molecular mechanisms, context-dependent signaling responses, and current translational challenges. Furthermore, existing knowledge gaps and future research priorities are discussed to facilitate the development of mechanism-based therapeutic strategies targeting Rho GTPases.<\/jats:p>","DOI":"10.3390\/cimb48070694","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:16:22Z","timestamp":1783592182000},"page":"694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Herbal Bioactives Targeting Rho GTPases: A Multi-Targeted Strategy for Mitigating Neuroinflammation in Alzheimer\u2019s and Parkinson\u2019s Diseases"],"prefix":"10.3390","volume":"48","author":[{"given":"Tzong-Shi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9047-8141","authenticated-orcid":false,"given":"I-Shiang","family":"Tzeng","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6319-6114","authenticated-orcid":false,"given":"Yi-Chyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5871-1030","authenticated-orcid":false,"given":"Mao-Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jalz.2016.02.010","article-title":"Neuroinflammation in Alzheimer\u2019s disease: Current evidence and future directions","volume":"12","author":"Calsolaro","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10753-022-01721-1","article-title":"Neuroinflammation in Alzheimer\u2019s Disease: Current Progress in Molecular Signaling and Therapeutics","volume":"46","author":"Thakur","year":"2023","journal-title":"Inflammation"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Al-Ghraiybah, N.F., Wang, J., Alkhalifa, A.E., Roberts, A.B., Raj, R., Yang, E., and Kaddoumi, A. (2022). Glial Cell-Mediated Neuroinflammation in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810572"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wang, C., Zong, S., Cui, X., Wang, X., Wu, S., Wang, L., Liu, Y., and Lu, Z. (2023). The effects of microglia-associated neuroinflammation on Alzheimer\u2019s disease. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1117172"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Isik, S., Yeman Kiyak, B., Akbayir, R., Seyhali, R., and Arpaci, T. (2023). Microglia Mediated Neuroinflammation in Parkinson\u2019s Disease. Cells, 12.","DOI":"10.3390\/cells12071012"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12974-022-02496-w","article-title":"The role of Toll-like receptors and neuroinflammation in Parkinson\u2019s disease","volume":"19","author":"Heidari","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1177\/1073858421991066","article-title":"Neuroinflammation in Parkinson\u2019s Disease: Triggers, Mechanisms, and Immunotherapies","volume":"28","author":"Wang","year":"2022","journal-title":"Neuroscientist"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1016\/j.cell.2024.02.030","article-title":"Cellular architecture of evolving neuroinflammatory lesions and multiple sclerosis pathology","volume":"187","author":"Kukanja","year":"2024","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1002\/glia.23940","article-title":"Altered astrocytic function in experimental neuroinflammation and multiple sclerosis","volume":"69","author":"Sousa","year":"2021","journal-title":"Glia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1126\/science.279.5350.509","article-title":"Rho GTPases and the actin cytoskeleton","volume":"279","author":"Hall","year":"1998","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s10059-010-0053-8","article-title":"Regulation of actin cytoskeleton dynamics in cells","volume":"29","author":"Lee","year":"2010","journal-title":"Mol. Cells"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3025948","DOI":"10.1155\/2016\/3025948","article-title":"Control of Dendritic Spine Morphological and Functional Plasticity by Small GTPases","volume":"2016","author":"Woolfrey","year":"2016","journal-title":"Neural Plast."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.tins.2005.01.008","article-title":"Spine architecture and synaptic plasticity","volume":"28","author":"Carlisle","year":"2005","journal-title":"Trends Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.aanat.2011.02.015","article-title":"Rho GTPases as regulators of morphological neuroplasticity","volume":"193","author":"Auer","year":"2011","journal-title":"Ann. Anat."},{"key":"ref_15","first-page":"652","article-title":"Rho\/ROCK pathway and neural regeneration: A potential therapeutic target for central nervous system and optic nerve damage","volume":"4","author":"Tan","year":"2011","journal-title":"Int. J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.4103\/1673-5374.170325","article-title":"The role of the Rho\/ROCK signaling pathway in inhibiting axonal regeneration in the central nervous system","volume":"10","author":"Liu","year":"2015","journal-title":"Neural Regen. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"L830","DOI":"10.1152\/ajplung.00467.2001","article-title":"Rho protein inactivation induced apoptosis of cultured human endothelial cells","volume":"283","author":"Hippenstiel","year":"2002","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/sj.cdd.4400987","article-title":"Rho GTPase signalling pathways in the morphological changes associated with apoptosis","volume":"9","author":"Coleman","year":"2002","journal-title":"Cell Death Differ."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1007\/s00702-017-1797-5","article-title":"Neurotrophic function of phytochemicals for neuroprotection in aging and neurodegenerative disorders: Modulation of intracellular signaling and gene expression","volume":"124","author":"Naoi","year":"2017","journal-title":"J. Neural Transm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.bbr.2017.11.003","article-title":"Phytochemical allylguaiacol exerts a neuroprotective effect on hippocampal cells and ameliorates scopolamine-induced memory impairment in mice","volume":"339","author":"Lim","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7340881","DOI":"10.1155\/2022\/7340881","article-title":"Blueberry Anthocyanins Extract Attenuates Acrylamide-Induced Oxidative Stress and Neuroinflammation in Rats","volume":"2022","author":"Fang","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Limanaqi, F., Biagioni, F., Busceti, C.L., Polzella, M., Fabrizi, C., and Fornai, F. (2020). Potential Antidepressant Effects of Scutellaria baicalensis, Hericium erinaceus and Rhodiola rosea. Antioxidants, 9.","DOI":"10.3390\/antiox9030234"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1179\/1476830512Y.0000000047","article-title":"Oil palm phenolics confer neuroprotective effects involving cognitive and motor functions in mice","volume":"16","author":"Leow","year":"2013","journal-title":"Nutr. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1007\/s12011-023-04041-z","article-title":"Inflammation in Metal-Induced Neurological Disorders and Neurodegenerative Diseases","volume":"202","author":"Wei","year":"2024","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kalyan, M., Tousif, A.H., Sonali, S., Vichitra, C., Sunanda, T., Praveenraj, S.S., Ray, B., Gorantla, V.R., Rungratanawanich, W., and Mahalakshmi, A.M. (2022). Role of Endogenous Lipopolysaccharides in Neurological Disorders. Cells, 11.","DOI":"10.3390\/cells11244038"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chen, Z., Wang, P., Cheng, H., Wang, N., Wu, M., Wang, Z., Wang, Z., Dong, W., Guan, D., and Wang, L. (2023). Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: Role of persistent oxidative stress and neuroinflammation. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1292014"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Boulamery, A., and Desplat-Jego, S. (2017). Regulation of Neuroinflammation: What Role for the Tumor Necrosis Factor-Like Weak Inducer of Apoptosis\/Fn14 Pathway? Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01534"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101333","DOI":"10.1016\/j.arr.2021.101333","article-title":"Emerging pathogenic role of peripheral blood factors following BBB disruption in neurodegenerative disease","volume":"68","author":"Jeon","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"975","DOI":"10.3233\/JAD-160612","article-title":"Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer\u2019s disease Neurons","volume":"57","author":"Rajmohan","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/ana.25159","article-title":"Neutrophil hyperactivation correlates with Alzheimer\u2019s disease progression","volume":"83","author":"Dong","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12979-024-00445-0","article-title":"Neuroinflammation in Alzheimer\u2019s disease: Insights from peripheral immune cells","volume":"21","author":"Zhang","year":"2024","journal-title":"Immun. Ageing"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1084\/jem.20052371","article-title":"Neutrophil-derived leukotriene B4 is required for inflammatory arthritis","volume":"203","author":"Chen","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nm.3913","article-title":"Neutrophils promote Alzheimer\u2019s disease-like pathology and cognitive decline via LFA-1 integrin","volume":"21","author":"Zenaro","year":"2015","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/s41593-018-0329-4","article-title":"Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer\u2019s disease mouse models","volume":"22","author":"Bracko","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.it.2009.07.012","article-title":"Opening the flood-gates: How neutrophil-endothelial interactions regulate permeability","volume":"30","author":"DiStasi","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1159\/000206974","article-title":"Regulation of extracellular chromatin release from neutrophils","volume":"1","author":"Neeli","year":"2009","journal-title":"J. Innate Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00401-010-0711-0","article-title":"The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson\u2019s disease and Parkinson\u2019s disease dementia","volume":"120","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_39","first-page":"879","article-title":"Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson\u2019s disease and dementia with Lewy bodies","volume":"152","author":"Baba","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10813","DOI":"10.1073\/pnas.152339799","article-title":"alpha -Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson\u2019s disease","volume":"99","author":"Ridet","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tang, Y. (2018). Editorial: Microglial Polarization in the Pathogenesis and Therapeutics of Neurodegenerative Diseases. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00154"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1742-2094-2-14","article-title":"Microglial inflammation in the parkinsonian substantia nigra: Relationship to alpha-synuclein deposition","volume":"2","author":"Croisier","year":"2005","journal-title":"J. Neuroinflamm."},{"key":"ref_43","first-page":"113","article-title":"Neuroimmunological processes in Parkinson\u2019s disease and their relation to alpha-synuclein: Microglia as the referee between neuronal processes and peripheral immunity","volume":"5","author":"Barnum","year":"2013","journal-title":"ASN Neuro"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1097\/NEN.0b013e31818e5e99","article-title":"Targeted overexpression of human alpha-synuclein triggers microglial activation and an adaptive immune response in a mouse model of Parkinson disease","volume":"67","author":"Theodore","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sanchez-Guajardo, V., Febbraro, F., Kirik, D., and Romero-Ramos, M. (2010). Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson\u2019s disease. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008784"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Fu, J., Chen, S., Liu, J., Yang, J., Ou, R., Zhang, L., Chen, X., and Shang, H. (2023). Serum inflammatory cytokines levels and the correlation analyses in Parkinson\u2019s disease. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1104393"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1600-0404.1999.tb00721.x","article-title":"Association of circulating TNF-alpha and IL-6 with ageing and parkinsonism","volume":"100","author":"Dobbs","year":"1999","journal-title":"Acta Neurol. Scand."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neulet.2009.10.062","article-title":"Serum levels of interleukin-6 are elevated in patients with Parkinson\u2019s disease and correlate with physical performance","volume":"468","author":"Scalzo","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.3390\/ijerph8072980","article-title":"Features of microglia and neuroinflammation relevant to environmental exposure and neurotoxicity","volume":"8","author":"Kraft","year":"2011","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Qin, J., Ma, Z., Chen, X., and Shu, S. (2023). Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1103416"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","article-title":"Microglia in neurodegenerative diseases: Mechanism and potential therapeutic targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"152706","DOI":"10.1016\/j.imbio.2023.152706","article-title":"TNF-alpha evokes blood-brain barrier dysfunction through activation of Rho-kinase and neurokinin 1 receptor","volume":"228","author":"Gao","year":"2023","journal-title":"Immunobiology"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hwang, J.S., Vo, T.T.L., Kim, M., Cha, E.H., Mun, K.C., Ha, E., and Seo, J.H. (2025). Involvement of RhoA\/ROCK Signaling Pathway in Methamphetamine-Induced Blood-Brain Barrier Disruption. Biomolecules, 15.","DOI":"10.3390\/biom15030340"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Fujita, Y., and Yamashita, T. (2014). Axon growth inhibition by RhoA\/ROCK in the central nervous system. Front. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00338"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1523\/JNEUROSCI.19-17-07537.1999","article-title":"Inactivation of Rho signaling pathway promotes CNS axon regeneration","volume":"19","author":"Lehmann","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11481-024-10118-w","article-title":"The Roles of RhoA\/ROCK\/NF-kappaB Pathway in Microglia Polarization Following Ischemic Stroke","volume":"19","author":"Lu","year":"2024","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e00115","DOI":"10.1042\/BSR20140021","article-title":"Rho protein GTPases and their interactions with NFkappaB: Crossroads of inflammation and matrix biology","volume":"34","author":"Tong","year":"2014","journal-title":"Biosci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3233\/JAD-2010-1203","article-title":"Altered distribution of RhoA in Alzheimer\u2019s disease and AbetaPP overexpressing mice","volume":"19","author":"Huesa","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/jnc.13688","article-title":"Rho-associated protein kinase 1 (ROCK1) is increased in Alzheimer\u2019s disease and ROCK1 depletion reduces amyloid-beta levels in brain","volume":"138","author":"Henderson","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.neuroscience.2016.03.042","article-title":"MiR-133b ameliorates axon degeneration induced by MPP(+) via targeting RhoA","volume":"325","author":"Niu","year":"2016","journal-title":"Neuroscience"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"105883","DOI":"10.1016\/j.neuint.2024.105883","article-title":"Ras, RhoA, and vascular pharmacology in neurodevelopment and aging","volume":"181","author":"Nussinov","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"173815","DOI":"10.1016\/j.ejphar.2020.173815","article-title":"Role of RhoA-ROCK signaling in Parkinson\u2019s disease","volume":"894","author":"Iyer","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9090","DOI":"10.1073\/pnas.1531903100","article-title":"Chronic stress and age-related increases in the proinflammatory cytokine IL-6","volume":"100","author":"Preacher","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1006\/bbrc.2000.2364","article-title":"Autocrine\/Paracrine secretion of IL-6 family cytokines causes angiotensin II-induced delayed STAT3 activation","volume":"269","author":"Sano","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1080\/10715760500176866","article-title":"Rac1-NADPH oxidase-regulated generation of reactive oxygen species mediates glutamate-induced apoptosis in SH-SY5Y human neuroblastoma cells","volume":"39","author":"Nikolova","year":"2005","journal-title":"Free Radic. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.freeradbiomed.2018.01.008","article-title":"Crosstalk between Rac1-mediated actin regulation and ROS production","volume":"116","author":"Acevedo","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.mcn.2009.03.007","article-title":"Proinflammatory cytokines provoke oxidative damage to actin in neuronal cells mediated by Rac1 and NADPH oxidase","volume":"41","author":"Barth","year":"2009","journal-title":"Mol. Cell Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"115218","DOI":"10.1016\/j.biopha.2023.115218","article-title":"TREM2: Potential therapeutic targeting of microglia for Alzheimer\u2019s disease","volume":"165","author":"Li","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"10984","DOI":"10.1096\/fj.202000550RR","article-title":"Activation of FAK\/Rac1\/Cdc42-GTPase signaling ameliorates impaired microglial migration response to Abeta(42) in triggering receptor expressed on myeloid cells 2 loss-of-function murine models","volume":"34","author":"Rong","year":"2020","journal-title":"FASEB J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"102586","DOI":"10.1016\/j.pneurobio.2024.102586","article-title":"A cytoskeleton symphony: Actin and microtubules in microglia dynamics and aging","volume":"234","author":"Socodato","year":"2024","journal-title":"Prog. Neurobiol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zhang, H., Ben Zablah, Y., Zhang, H., and Jia, Z. (2021). Rho Signaling in Synaptic Plasticity, Memory, and Brain Disorders. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.729076"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1083\/jcb.200809151","article-title":"Synaptic activity prompts gamma-secretase-mediated cleavage of EphA4 and dendritic spine formation","volume":"185","author":"Inoue","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/s41380-021-01092-3","article-title":"Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: Pathophysiological implications","volume":"27","author":"Yan","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"11143","DOI":"10.1074\/jbc.RA118.003276","article-title":"Interleukin-6 promotes pancreatic cancer cell migration by rapidly activating the small GTPase CDC42","volume":"293","author":"Razidlo","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/srep00809","article-title":"ROCK\/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo","volume":"2","author":"Barcia","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Mayer, M.G., and Fischer, T. (2024). Microglia at the blood brain barrier in health and disease. Front. Cell Neurosci., 18.","DOI":"10.3389\/fncel.2024.1360195"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1083\/jcb.201003008","article-title":"Actin in dendritic spines: Connecting dynamics to function","volume":"189","author":"Hotulainen","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Park, G., Jin, Z., Lu, H., and Du, J. (2024). Clearing Amyloid-Beta by Astrocytes: The Role of Rho GTPases Signaling Pathways as Potential Therapeutic Targets. Brain Sci., 14.","DOI":"10.3390\/brainsci14121239"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/tra.12906","article-title":"Endocytic pathways of pathogenic protein aggregates in neurodegenerative diseases","volume":"24","author":"Hivare","year":"2023","journal-title":"Traffic"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Valappil, D.K., Mini, N.J., Dilna, A., and Nath, S. (2022). Membrane interaction to intercellular spread of pathology in Alzheimer\u2019s disease. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.936897"},{"key":"ref_81","first-page":"665","article-title":"Curcumin blocks migration and invasion of mouse-rat hybrid retina ganglion cells (N18) through the inhibition of MMP-2, -9, FAK, Rho A and Rock-1 gene expression","volume":"23","author":"Lin","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Little, P.J., Xu, S., and Kamato, D. (2021). Curcumin Inhibits Lysophosphatidic Acid Mediated MCP-1 Expression via Blocking ROCK Signalling. Molecules, 26.","DOI":"10.3390\/molecules26082320"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.biomaterials.2016.10.032","article-title":"Combined polymer-curcumin conjugate and ependymal progenitor\/stem cell treatment enhances spinal cord injury functional recovery","volume":"113","author":"England","year":"2017","journal-title":"Biomaterials"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Glotfelty, E.J., Tovar, Y.R.L.B., Hsueh, S.C., Tweedie, D., Li, Y., Harvey, B.K., Hoffer, B.J., Karlsson, T.E., Olson, L., and Greig, N.H. (2023). The RhoA-ROCK1\/ROCK2 Pathway Exacerbates Inflammatory Signaling in Immortalized and Primary Microglia. Cells, 12.","DOI":"10.3390\/cells12101367"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1182\/blood-2009-08-237222","article-title":"ROCK1 functions as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability","volume":"115","author":"Vemula","year":"2010","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"25342","DOI":"10.1038\/srep25342","article-title":"Resveratrol Inhibition of Rac1-Derived Reactive Oxygen Species by AMPK Decreases Blood Pressure in a Fructose-Induced Rat Model of Hypertension","volume":"6","author":"Cheng","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1111\/bph.12648","article-title":"Resveratrol decreases fructose-induced oxidative stress, mediated by NADPH oxidase via an AMPK-dependent mechanism","volume":"171","author":"Cheng","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Payne, A., Taka, E., Adinew, G.M., and Soliman, K.F.A. (2023). Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells. Brain Sci., 13.","DOI":"10.3390\/brainsci13040632"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Kim, S.R., Seong, K.J., Kim, W.J., and Jung, J.Y. (2022). Epigallocatechin Gallate Protects against Hypoxia-Induced Inflammation in Microglia via NF-kappaB Suppression and Nrf-2\/HO-1 Activation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23074004"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"115653","DOI":"10.1016\/j.biopha.2023.115653","article-title":"Quercetin improves cerebral ischemia\/reperfusion injury by promoting microglia\/macrophages M2 polarization via regulating PI3K\/Akt\/NF-kappaB signaling pathway","volume":"168","author":"Li","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1499-3872(16)60164-9","article-title":"Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats","volume":"16","author":"Kabirifar","year":"2017","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/aps.2016.125","article-title":"Advances in the study of berberine and its derivatives: A focus on anti-inflammatory and anti-tumor effects in the digestive system","volume":"38","author":"Zou","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Deng, M., Yan, W., Gu, Z., Li, Y., Chen, L., and He, B. (2023). Anti-Neuroinflammatory Potential of Natural Products in the Treatment of Alzheimer\u2019s Disease. Molecules, 28.","DOI":"10.3390\/molecules28031486"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/S1567-5769(02)00085-1","article-title":"Inhibition of TNF-alpha, IL-1beta, and IL-6 productions and NF-kappa B activation in lipopolysaccharide-activated RAW 264.7 macrophages by catalposide, an iridoid glycoside isolated from Catalpa ovata G. Don (Bignoniaceae)","volume":"2","author":"An","year":"2002","journal-title":"Int. Immunopharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Subedi, L., Lee, S.E., Madiha, S., Gaire, B.P., Jin, M., Yumnam, S., and Kim, S.Y. (2020). Phytochemicals against TNFalpha-Mediated Neuroinflammatory Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030764"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Yu, Y., Shen, Q., Lai, Y., Park, S.Y., Ou, X., Lin, D., Jin, M., and Zhang, W. (2018). Anti-inflammatory Effects of Curcumin in Microglial Cells. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00386"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Liao, H., Huang, J., Liu, J., Chen, Y., Zhu, H., Li, X., Wen, J., Xiang, Q., and Yang, Q. (2023). Resveratrol Inhibits Activation of Microglia after Stroke through Triggering Translocation of Smo to Primary Cilia. J. Pers. Med., 13.","DOI":"10.3390\/jpm13020268"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13567-023-01149-x","article-title":"Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis","volume":"54","author":"Feng","year":"2023","journal-title":"Vet. Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kalu, A., and Ray, S.K. (2025). Epigallocatechin-3-Gallate, Quercetin, and Kaempferol for Treatment of Parkinson\u2019s Disease Through Prevention of Gut Dysbiosis and Attenuation of Multiple Molecular Mechanisms of Pathogenesis. Brain Sci., 15.","DOI":"10.3390\/brainsci15020144"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Martinez-Coria, H., Arrieta-Cruz, I., Gutierrez-Juarez, R., and Lopez-Valdes, H.E. (2023). Anti-Inflammatory Effects of Flavonoids in Common Neurological Disorders Associated with Aging. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054297"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1002\/ptr.8430","article-title":"Berberine Inhibits the Disruption of the Blood-Brain Barrier and Glial Cell Activation in a Rat Model of Acute Hepatic Encephalopathy","volume":"39","author":"Ali","year":"2025","journal-title":"Phytother. Res."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Huang, S., Liu, H., Lin, Y., Liu, M., Li, Y., Mao, H., Zhang, Z., Zhang, Y., Ye, P., and Ding, L. (2020). Berberine Protects Against NLRP3 Inflammasome via Ameliorating Autophagic Impairment in MPTP-Induced Parkinson\u2019s Disease Model. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.618787"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"He, T., Lin, X., Su, A., Zhang, Y., Xing, Z., Mi, L., Wei, T., Li, Z., and Wu, W. (2023). Mitochondrial dysfunction-targeting therapeutics of natural products in Parkinson\u2019s disease. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1117337"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Misrani, A., Tabassum, S., and Yang, L. (2021). Mitochondrial Dysfunction and Oxidative Stress in Alzheimer\u2019s Disease. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.617588"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jss.2016.08.090","article-title":"Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice","volume":"207","author":"Yuan","year":"2017","journal-title":"J. Surg. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1007\/s12031-013-9989-4","article-title":"Curcumin ameliorates the permeability of the blood-brain barrier during hypoxia by upregulating heme oxygenase-1 expression in brain microvascular endothelial cells","volume":"51","author":"Wang","year":"2013","journal-title":"J. Mol. Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"783","DOI":"10.3892\/etm.2021.10215","article-title":"Curcumin ameliorates ischemic stroke injury in rats by protecting the integrity of the blood-brain barrier","volume":"22","author":"Wu","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1172\/JCI30556","article-title":"Interplay of IKK\/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy","volume":"117","author":"Acharyya","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3474","DOI":"10.4049\/jimmunol.163.6.3474","article-title":"Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity","volume":"163","author":"Jobin","year":"1999","journal-title":"J. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1159\/000430126","article-title":"Curcumin Modulates Macrophage Polarization Through the Inhibition of the Toll-Like Receptor 4 Expression and its Signaling Pathways","volume":"36","author":"Zhou","year":"2015","journal-title":"Cell Physiol. Biochem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1179\/2045772313Y.0000000179","article-title":"Curcumin modulates TLR4\/NF-kappaB inflammatory signaling pathway following traumatic spinal cord injury in rats","volume":"38","author":"Ni","year":"2015","journal-title":"J. Spinal Cord. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/1742-2094-11-59","article-title":"Curcumin attenuates acute inflammatory injury by inhibiting the TLR4\/MyD88\/NF-kappaB signaling pathway in experimental traumatic brain injury","volume":"11","author":"Zhu","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.pbb.2005.08.009","article-title":"Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats","volume":"82","author":"Xu","year":"2005","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.brainres.2008.02.087","article-title":"Visual-auditory spatial processing in auditory cortical neurons","volume":"1242","author":"Bizley","year":"2008","journal-title":"Brain Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-0-387-46401-5_3","article-title":"Antioxidant and anti-inflammatory properties of curcumin","volume":"595","author":"Menon","year":"2007","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Islam, M.A., Alam, F., Kamal, M.A., Gan, S.H., Sasongko, T.H., and Wong, K.K. (2017). Presence of Anticardiolipin Antibodies in Patients with Dementia: A Systematic Review and Meta-Analysis. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00250"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Rege, S.D., Geetha, T., Griffin, G.D., Broderick, T.L., and Babu, J.R. (2014). Neuroprotective effects of resveratrol in Alzheimer disease pathology. Front. Aging Neurosci., 6.","DOI":"10.3389\/fnagi.2014.00218"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1152\/japplphysiol.00686.2017","article-title":"Resveratrol regulates blood pressure by enhancing AMPK signaling to downregulate a Rac1-derived NADPH oxidase in the central nervous system","volume":"125","author":"Yeh","year":"2018","journal-title":"J. Appl. Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Bartra, C., Yuan, Y., Vuraic, K., Valdes-Quiroz, H., Garcia-Baucells, P., Slevin, M., Pastorello, Y., Sunol, C., and Sanfeliu, C. (2024). Resveratrol Activates Antioxidant Protective Mechanisms in Cellular Models of Alzheimer\u2019s Disease Inflammation. Antioxidants, 13.","DOI":"10.3390\/antiox13020177"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Xu, L., Botchway, B.O.A., Zhang, S., Zhou, J., and Liu, X. (2018). Inhibition of NF-kappaB Signaling Pathway by Resveratrol Improves Spinal Cord Injury. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00690"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Watroba, M., and Szukiewicz, D. (2025). Anti-Inflammatory Properties of Resveratrol. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262311710"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"22048","DOI":"10.1074\/jbc.M114.568790","article-title":"Sirtuin-1 (SIRT1) is required for promoting chondrogenic differentiation of mesenchymal stem cells","volume":"289","author":"Buhrmann","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"26216","DOI":"10.1038\/s41598-024-76825-9","article-title":"Resveratrol improved mitochondrial biogenesis by activating SIRT1\/PGC-1alpha signal pathway in SAP","volume":"14","author":"Wu","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1161\/ATVBAHA.108.166991","article-title":"SIRT1, a longevity gene, downregulates angiotensin II type 1 receptor expression in vascular smooth muscle cells","volume":"28","author":"Miyazaki","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Zhao, A., Liu, N., Yao, M., Zhang, Y., Yao, Z., Feng, Y., Liu, J., and Zhou, G. (2022). A Review of Neuroprotective Effects and Mechanisms of Ginsenosides from Panax Ginseng in Treating Ischemic Stroke. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.946752"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Im, D.S. (2020). Pro-Resolving Effect of Ginsenosides as an Anti-Inflammatory Mechanism of Panax ginseng. Biomolecules, 10.","DOI":"10.3390\/biom10030444"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2147\/CEG.S130449","article-title":"Laparoscopic esophageal myotomy versus pneumatic dilation in the treatment of idiopathic achalasia: A meta-analysis of randomized controlled trials","volume":"10","author":"Baniya","year":"2017","journal-title":"Clin. Exp. Gastroenterol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"e08354","DOI":"10.1016\/j.heliyon.2021.e08354","article-title":"The promising therapeutic potentials of ginsenosides mediated through p38 MAPK signaling inhibition","volume":"7","author":"Arafa","year":"2021","journal-title":"Heliyon"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.apsb.2025.10.018","article-title":"Targeting glial cells: Unveiling the neuroprotective mechanisms of Ginseng in the brain microenvironment","volume":"16","author":"Wang","year":"2026","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Garre-Morata, L., de Haro, T., Villen, R.G., Fernandez-Lopez, M.L., Escames, G., Molina-Carballo, A., and Acuna-Castroviejo, D. (2024). Changes in Cortisol and in Oxidative\/Nitrosative Stress Indicators after ADHD Treatment. Antioxidants, 13.","DOI":"10.3390\/antiox13010092"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.4103\/1673-5374.139474","article-title":"Possible protective action of neurotrophic factors and natural compounds against common neurodegenerative diseases","volume":"9","author":"Numakawa","year":"2014","journal-title":"Neural Regen. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jgr.2024.03.003","article-title":"Ginseng-derived compounds as potential anticancer agents targeting cancer stem cells","volume":"48","author":"Lee","year":"2024","journal-title":"J. Ginseng Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1007\/s11064-015-1647-5","article-title":"Neuroprotective Effects of (-)-Epigallocatechin-3-Gallate Against Focal Cerebral Ischemia\/Reperfusion Injury in Rats Through Attenuation of Inflammation","volume":"40","author":"Zhang","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Cheng, C.Y., Barro, L., Tsai, S.T., Feng, T.W., Wu, X.Y., Chao, C.W., Yu, R.S., Chin, T.Y., and Hsieh, M.F. (2021). Epigallocatechin-3-Gallate-Loaded Liposomes Favor Anti-Inflammation of Microglia Cells and Promote Neuroprotection. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063037"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"8198","DOI":"10.12659\/MSM.911175","article-title":"Epigallocatechin Gallate Is the Most Effective Catechin Against Antioxidant Stress via Hydrogen Peroxide and Radical Scavenging Activity","volume":"24","author":"He","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Goncalves, P.B., Sodero, A.C.R., and Cordeiro, Y. (2021). Green Tea Epigallocatechin-3-gallate (EGCG) Targeting Protein Misfolding in Drug Discovery for Neurodegenerative Diseases. Biomolecules, 11.","DOI":"10.3390\/biom11050767"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/nsmb.1437","article-title":"EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers","volume":"15","author":"Ehrnhoefer","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e00347","DOI":"10.1016\/j.neurot.2024.e00347","article-title":"Berberine inhibits NLRP3 inflammasome activation and proinflammatory macrophage M1 polarization to accelerate peripheral nerve regeneration","volume":"21","author":"Sun","year":"2024","journal-title":"Neurotherapeutics"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"129","DOI":"10.33549\/physiolres.935410","article-title":"Berberine Exerts Neuroprotective Effects in Alzheimer\u2019s Disease by Switching Microglia M1\/M2 Polarization Through PI3K-AKT Signaling","volume":"74","author":"Hu","year":"2025","journal-title":"Physiol. Res."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Baba, R.A., Mir, H.A., Mokhdomi, T.A., Bhat, H.F., Ahmad, A., and Khanday, F.A. (2024). Quercetin suppresses ROS production and migration by specifically targeting Rac1 activation in gliomas. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1318797"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2986796","DOI":"10.1155\/2016\/2986796","article-title":"Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More","volume":"2016","author":"Costa","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Block, M.L. (2008). NADPH oxidase as a therapeutic target in Alzheimer\u2019s disease. BMC Neurosci., 9.","DOI":"10.1186\/1471-2202-9-S2-S8"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.freeradbiomed.2024.06.007","article-title":"NOX1 triggers ferroptosis and ferritinophagy, contributes to Parkinson\u2019s disease","volume":"222","author":"Wang","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"105754","DOI":"10.1016\/j.nbd.2022.105754","article-title":"NADPH oxidase 2 activity in Parkinson\u2019s disease","volume":"170","author":"Keeney","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/glia.22745","article-title":"RhoA\/ROCK pathway mediates p38 MAPK activation and morphological changes downstream of P2Y12\/13 receptors in spinal microglia in neuropathic pain","volume":"63","author":"Tatsumi","year":"2015","journal-title":"Glia"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"921941","DOI":"10.1155\/2012\/921941","article-title":"Quercetin and sesamin protect dopaminergic cells from MPP+-induced neuroinflammation in a microglial (N9)-neuronal (PC12) coculture system","volume":"2012","author":"Bournival","year":"2012","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1002\/jcb.26392","article-title":"Quercetin reduces neural tissue damage and promotes astrocyte activation after spinal cord injury in rats","volume":"119","author":"Wang","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Fakhri, S., Gravandi, M.M., Abdian, S., Moradi, S.Z., and Echeverria, J. (2022). Quercetin Derivatives in Combating Spinal Cord Injury: A Mechanistic and Systematic Review. Life, 12.","DOI":"10.3390\/life12121960"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"7099","DOI":"10.2147\/JIR.S480644","article-title":"Quercetin Attenuates MRGPRX2-Mediated Mast Cell Degranulation via the MyD88\/IKK\/NF-kappaB and PI3K\/AKT\/Rac1\/Cdc42 Pathway","volume":"17","author":"Zhao","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ijdevneu.2019.02.005","article-title":"Quercetin promotes learning and memory performance concomitantly with neural stem\/progenitor cell proliferation and neurogenesis in the adult rat dentate gyrus","volume":"74","author":"Karimipour","year":"2019","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1096\/fj.12-212118","article-title":"Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer\u2019s disease","volume":"27","author":"Ho","year":"2013","journal-title":"FASEB J."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Khan, A., Ali, T., Rehman, S.U., Khan, M.S., Alam, S.I., Ikram, M., Muhammad, T., Saeed, K., Badshah, H., and Kim, M.O. (2018). Neuroprotective Effect of Quercetin Against the Detrimental Effects of LPS in the Adult Mouse Brain. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01383"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.freeradbiomed.2024.05.044","article-title":"Oligomeric Tau-induced oxidative damage and functional alterations in cerebral endothelial cells: Role of RhoA\/ROCK signaling pathway","volume":"221","author":"Hossen","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_154","first-page":"4683","article-title":"Quercetin improves blood-brain barrier dysfunction in rats with cerebral ischemia reperfusion via Wnt signaling pathway","volume":"11","author":"Jin","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.2147\/DMSO.S491175","article-title":"Quercetin Alleviates Diabetic Peripheral Neuropathy by Regulating Axon Guidance Factors and Inhibiting the Rho\/ROCK Pathway in vivo and in vitro","volume":"17","author":"Song","year":"2024","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"294","DOI":"10.2478\/intox-2018-0029","article-title":"Impact of quercetin on tight junctional proteins and BDNF signaling molecules in hippocampus of PCBs-exposed rats","volume":"11","author":"Selvakumar","year":"2018","journal-title":"Interdiscip. Toxicol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia Function in the Central Nervous System During Health and Neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1016\/j.yexcr.2013.06.016","article-title":"Rho GTPases in neurodegeneration diseases","volume":"319","author":"DeGeer","year":"2013","journal-title":"Exp. Cell Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1111\/1759-7714.13925","article-title":"Quercetin induces pro-apoptotic autophagy via SIRT1\/AMPK signaling pathway in human lung cancer cell lines A549 and H1299 in vitro","volume":"12","author":"Guo","year":"2021","journal-title":"Thorac. Cancer"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"8712","DOI":"10.1039\/D4FO02602K","article-title":"Quercetin ameliorates neuroinflammatory and neurodegenerative biomarkers in the brain and improves neurobehavioral parameters in a repeated intranasal amyloid-beta exposed model of Alzheimer\u2019s disease","volume":"15","author":"Lasure","year":"2024","journal-title":"Food Funct."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1007\/s10787-025-01712-2","article-title":"Quercetin protects against neuronal toxicity by activating the PI3K\/Akt\/GSK-3beta pathway in vivo models of MPTP-induced Parkinson\u2019s disease","volume":"33","author":"Li","year":"2025","journal-title":"Inflammopharmacology"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Yang, J., Ma, Y.M., Yang, L., Li, P., Jing, L., Li, P.A., and Zhang, J.Z. (2025). Quercetin alleviates cerebral ischemia and reperfusion injury in hyperglycemic animals by reducing endoplasmic reticulum stress through activating SIRT1. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0321006"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1080\/13880209.2017.1288262","article-title":"Withaferin A protects against spinal cord injury by inhibiting apoptosis and inflammation in mice","volume":"55","author":"Yan","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Qiu, X., Huang, R., Xie, J., Luo, S., Cheng, X., Cui, J., and Hu, D. (2025). Recent Advances in the Therapeutic Effects and Molecular Mechanisms of Baicalin. Biology, 14.","DOI":"10.3390\/biology14060637"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"108532","DOI":"10.1016\/j.intimp.2022.108532","article-title":"Baicalin clears inflammation by enhancing macrophage efferocytosis via inhibition of RhoA\/ROCK signaling pathway and regulating macrophage polarization","volume":"105","author":"Cai","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1007\/s11011-017-0075-4","article-title":"Huperzine A alleviates neuroinflammation, oxidative stress and improves cognitive function after repetitive traumatic brain injury","volume":"32","author":"Mei","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/1440-1681.13064","article-title":"Huperzine A ameliorates cognitive dysfunction and neuroinflammation in kainic acid-induced epileptic rats by antioxidant activity and NLRP3\/caspase-1 pathway inhibition","volume":"46","author":"Sadr","year":"2019","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.bbi.2020.09.017","article-title":"Andrographolide suppresses NLRP3 inflammasome activation in microglia through induction of parkin-mediated mitophagy in in-vitro and in-vivo models of Parkinson disease","volume":"91","author":"Ahmed","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Bosco, F., Ruga, S., Citraro, R., Leo, A., Guarnieri, L., Maiuolo, J., Oppedisano, F., Macri, R., Scarano, F., and Nucera, S. (2023). The Effects of Andrographis paniculata (Burm.F.) Wall. Ex Nees and Andrographolide on Neuroinflammation in the Treatment of Neurodegenerative Diseases. Nutrients, 15.","DOI":"10.3390\/nu15153428"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1124\/jpet.103.059683","article-title":"Andrographolide reduces inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuron-glia cultures by inhibiting microglial activation","volume":"308","author":"Wang","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/694\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:22:15Z","timestamp":1783657335000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":170,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cimb48070694"],"URL":"https:\/\/doi.org\/10.3390\/cimb48070694","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]}}}