{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:07:18Z","timestamp":1789708038445,"version":"4.0.1"},"reference-count":77,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Jilin Province","award":["20260102166JC"],"award-info":[{"award-number":["20260102166JC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Paeoniflorin, a bioactive monoterpene glycoside derived from Paeonia lactiflora, has shown neuroprotective effects primarily associated with the promotion of brain-derived neurotrophic factor secretion. This study aims to elucidate the therapeutic potential of paeoniflorin in models of Parkinson\u2019s disease and to investigate the role of the BDNF-mediated PI3K\/Akt and ERK1\/2\/p90RSK\/CREB signaling pathways. Notably, paeoniflorin improved motor function, reduced dopamine catabolism, and attenuated dopaminergic neuronal loss in PD mice by regulating dopamine catabolism and inhibiting turnover, indicating dopaminergic protection. In vitro, paeoniflorin pretreatment enhanced cell viability, reduced LDH release, suppressed ROS and intracellular Ca2+ overload, stabilized mitochondrial membrane potential, and attenuated MPP+-induced apoptosis. A key innovation is the dual activation and coordinated activation of the two BDNF-dependent pathways: LY294002 abolished paeoniflorin-induced BDNF\/PI3K\/Akt activation, while PD98059 and ERK1\/2 siRNA specifically suppressed paeoniflorin-triggered phosphorylation of ERK1\/2, p90RSK, and CREB. Ultimately, paeoniflorin exerts robust neuroprotection against MPTP\/MPP+ neurotoxicity by synergistically activating BDNF-downstream PI3K\/Akt and ERK\/CREB axes. This delineation of a dual-pathway mechanism provides novel insight into the pharmacological action of paeoniflorin and supports its potential as a multifaceted therapeutic agent for Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/cimb48090944","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:06:37Z","timestamp":1789549597000},"page":"944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Mechanisms of Paeoniflorin in Parkinson\u2019s Models: Involvement of BDNF-Dependent PI3K\/Akt and ERK\/CREB Pathways"],"prefix":"10.3390","volume":"48","author":[{"given":"Chang","family":"Jin","sequence":"first","affiliation":[{"name":"College of Life Science, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Zhifeng","family":"Cheng","sequence":"additional","affiliation":[{"name":"College of Life Science, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2629-7653","authenticated-orcid":false,"given":"Meizhu","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Central Laboratory, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-6479","authenticated-orcid":false,"given":"Kai","family":"Song","sequence":"additional","affiliation":[{"name":"College of Life Science, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5212-3609","authenticated-orcid":false,"given":"Yongxing","family":"Ai","sequence":"additional","affiliation":[{"name":"College of Animal Science, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41582-019-0301-2","article-title":"LRRK2 in Parkinson disease: Challenges of clinical trials","volume":"16","author":"Tolosa","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1474-4422(21)00030-2","article-title":"Challenges in the diagnosis of Parkinson\u2019s disease","volume":"20","author":"Tolosa","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00702-017-1686-y","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"124","author":"Tysnes","year":"2017","journal-title":"J. Neural Transm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"114642","DOI":"10.1016\/j.expneurol.2023.114642","article-title":"TMT-based quantitative proteomics analysis of neuroprotective effects of Forsythoside A on the MPTP-induced Parkinson\u2019s disease mouse model","volume":"373","author":"Niu","year":"2024","journal-title":"Exp. Neurol."},{"key":"ref_5","first-page":"127","article-title":"Pharmacological treatment of tremor in Parkinson\u2019s disease revisited","volume":"13","author":"Pirker","year":"2023","journal-title":"J. Park. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/mds.27338","article-title":"Long-term safety and efficacy of levodopa-carbidopa intestinal gel in advanced Parkinson\u2019s disease","volume":"33","author":"Fernandez","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1093\/advances\/nmab060","article-title":"Dietary approaches to improve efffcacy and control side effects of levodopa therapy in Parkinson\u2019s disease: A systematic review","volume":"12","author":"Boelens","year":"2021","journal-title":"Adv. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"114821","DOI":"10.1016\/j.jep.2021.114821","article-title":"Antioxidative role of Traditional Chinese Medicine in Parkinson\u2019s disease","volume":"285","author":"Muhammad","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110968","DOI":"10.1016\/j.biopha.2020.110968","article-title":"Traditional Chinese medicine compounds regulate autophagy for treating neurodegenerative disease: A mechanism review","volume":"133","author":"Wang","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9923331","DOI":"10.1155\/2021\/9923331","article-title":"The Positive Role and Mechanism of Herbal Medicine in Parkinson\u2019s Disease","volume":"2021","author":"Yin","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/sj.bjp.0706732","article-title":"Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson\u2019s disease by activation of adenosine A1 receptor","volume":"148","author":"Liu","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Feng, Z., Jin, C., Zhang, Y., Xue, H., Ai, Y., Wang, J., Zheng, M., and Shi, D. (2025). Tandem mass tags quantitative proteomics reveal the mechanism by which Paeoniflorin regulates the PI3K\/AKT and BDNF\/CREB signaling pathways to inhibit Parkinson\u2019s Disease. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136498"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hu, P.Y., Liu, D., Zheng, Q., Wu, Q., Tang, Y., and Yang, M. (2016). Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood-Brain Barrier in Vitro Model. Molecules, 21.","DOI":"10.3390\/molecules21030300"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1016\/j.fct.2012.05.045","article-title":"Salidroside protects PC12 cells from MPP+-induced apoptosis via activation of the PI3K\/Akt pathway","volume":"50","author":"Zhang","year":"2012","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"175491","DOI":"10.1016\/j.ejphar.2023.175491","article-title":"The protection impact of tectoridin on PC12 cell preventing OGD\/R-caused damage through PI3K\/AKT signaling channel","volume":"941","author":"Chen","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Palasz, E., Wysocka, A., Gasiorowska, A., Chalimoniuk, M., Niewiadomski, W., and Niewiadomska, G. (2020). BDNF as a Promising Therapeutic Agent in Parkinson\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031170"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"113091","DOI":"10.1016\/j.fct.2022.113091","article-title":"Curcumin can improve Parkinson\u2019s disease via activating BDNF\/PI3k\/Akt signaling pathways","volume":"164","author":"Jin","year":"2022","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/S0006-8993(99)02148-4","article-title":"Oxidative stress and Ca2+ influx upregulate calpain and induce apoptosis in PC12 cells","volume":"852","author":"Ray","year":"2000","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.mce.2015.04.008","article-title":"Melanocortin 4 receptor activates ERK-cFos pathway to increase brain-derived neurotrophic factor expression in rat astrocytes and hypothalamus","volume":"411","author":"Saba","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.neuropharm.2017.01.009","article-title":"Neuroprotection by Paeoniflorin in the MPTP mouse model of Parkinson\u2019s disease","volume":"116","author":"Zheng","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e9195","DOI":"10.1097\/MD.0000000000009195","article-title":"Degeneration of the corticofugal tract from the secondary motor area in a Parkinson\u2019s disease patient with limb-kinetic apraxia: A case report","volume":"96","author":"Lee","year":"2017","journal-title":"Medicine"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yu, H., Li, X., Liu, Y., and Zhang, Y. (2022). A review for the pharmacological effects of paeoni-florin in the nervous system. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.898955"},{"key":"ref_23","first-page":"435","article-title":"A simple quantitative bradykinesia test in MPTP-treated mice","volume":"50","author":"Ogawa","year":"1985","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"114901","DOI":"10.1016\/j.bbr.2024.114901","article-title":"Pros and cons of narrow- versus wide-compartment rotarod apparatus: An experimental study in mice","volume":"468","author":"Keane","year":"2024","journal-title":"Behav. Brain Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lu, R., Zhang, L., Wang, H., Li, M., Feng, W., and Zheng, X. (2023). Echinacoside exerts antidepressant-like effects through enhancing BDNF-CREB pathway and inhibiting neuroinflammation via regulating microglia M1\/M2 polarization and JAK1\/STAT3 pathway. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.993483"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4791","DOI":"10.1002\/ptr.7946","article-title":"Paeoniflorin suppresses neuronal ferroptosis to improve the cognitive behaviors in Alzheimer\u2019s disease mice","volume":"37","author":"Zhai","year":"2023","journal-title":"Phytother. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hu, Z., Wang, X., Shi, T., Yang, L., Zhang, B., Shang, B., He, R., Yi, S., He, J., and Hu, J. (2025). Paeoniflorin Alleviates Lipopolysaccharide-Induced Neuroinflammation and Depression Through the Keap1\/Nrf2\/HO-1 Signaling Pathway. Antioxidants, 14.","DOI":"10.3390\/antiox14050585"},{"key":"ref_28","first-page":"6730559","article-title":"Paeoniflorin Enhances the Sensitivity of ER-Positive Breast Cancer Cells to Tamoxifen through Promoting Sirtuin 4","volume":"2022","author":"Zhang","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"106675","DOI":"10.1016\/j.biocel.2024.106675","article-title":"Paeoniflorin regulates microglia-astrocyte crosstalk, inhibits inflammatory response, and alleviates neuropathic pain through HSP90AA1\/HMGB1 signaling pathway","volume":"176","author":"Luo","year":"2024","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"112182","DOI":"10.1016\/j.jep.2019.112182","article-title":"Total glucosides of paeony (TGP) extracted from Radix Paeoniae Alba exerts neuroprotective effects in MPTP-induced experimental parkinsonism by regulating the cAMP\/PKA\/CREB signaling pathway","volume":"245","author":"Zheng","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","first-page":"555","article-title":"Studies on the Chemical Constituents of the Chinese Medical Drug, Root of Paeonia lactiflora Pall","volume":"10","author":"Fu","year":"1963","journal-title":"Acta Pharm. Sin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1055\/s-2006-957934","article-title":"Endothelium-dependent vasodilator effect of extract prepared from the roots of Paeonia lactiflora on isolated rat aorta","volume":"62","author":"Goto","year":"1996","journal-title":"Planta Medica"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"135016","DOI":"10.1016\/j.neulet.2020.135016","article-title":"Paeoniflorin exerts neuroprotective effects in a transgenic mouse model of Alzheimer\u2019s disease via activation of adenosine A1 receptor","volume":"730","author":"Kong","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1007\/s11101-017-9527-z","article-title":"Neuroprotective effects of paeoniflorin in neurodegenerative diseases of the central nervous system","volume":"16","author":"Manayi","year":"2017","journal-title":"Phytochem. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.3892\/etm.2015.2360","article-title":"Neuroprotective effect of paeoniflorin on H2O2-induced apoptosis in PC12 cells by modulation of reactive oxygen species and the inflammatory response","volume":"9","author":"Li","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s12974-025-03455-x","article-title":"Repurposing of epalrestat for neuroprotection in parkinson\u2019s disease via activation of the KEAP1\/Nrf2 pathway","volume":"22","author":"Jia","year":"2025","journal-title":"J. Neuroinflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41531-025-01029-5","article-title":"Butyrate improves abnormal sleep architecture in a Parkinson\u2019s disease mouse model via BDNF\/TrkB signaling","volume":"11","author":"Duan","year":"2025","journal-title":"npj Park. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.jare.2025.05.039","article-title":"Targeting the bile acid receptor TGR5 with Gentiopicroside to activate Nrf2 antioxidant signaling and mitigate Parkinson\u2019s disease in an MPTP mouse model","volume":"80","author":"Gao","year":"2026","journal-title":"Adv. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107134","DOI":"10.1016\/j.ejps.2025.107134","article-title":"Enhanced stability of levodopa and benserazide fixed-dose combination tablets through optimized production processes","volume":"211","author":"Pinarbasli","year":"2025","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1007\/s11064-016-1834-z","article-title":"Protective Effects of Paeoniflorin Against MPP+-induced Neurotoxicity in PC12 Cells","volume":"41","author":"Zheng","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101788","DOI":"10.1016\/j.jchemneu.2020.101788","article-title":"Dopamine, a key factor of mitochondrial damage and neuronal toxicity on rotenone exposure and also parkinsonic motor dysfunction-Impact of asiaticoside with a probable vesicular involvement","volume":"106","author":"Margabandhu","year":"2020","journal-title":"J. Chem. Neuroanat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"103617","DOI":"10.1016\/j.semcdb.2025.103617","article-title":"A near death experience: The secret stem cell life of caspase-3","volume":"171","author":"Sarji","year":"2025","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1159\/000477592","article-title":"Calcium Channel Opening Rather than the Release of ATP Causes the Apoptosis of Osteoblasts Induced by Overloaded Mechanical Stimulation","volume":"42","author":"Liu","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00232-014-9652-1","article-title":"Agomelatine and duloxetine synergistically modulates apoptotic pathway by inhibiting oxidative stress triggered intracellular calcium entry in neuronal PC12 cells: Role of TRPM2 and voltage-gated calcium channels","volume":"247","author":"Akpinar","year":"2014","journal-title":"J. Membr. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"964518","DOI":"10.1155\/2015\/964518","article-title":"Mechanisms of Neuronal Protection against Excitotoxicity, Endoplasmic Reticulum Stress, and Mitochondrial Dysfunction in Stroke and Neurodegenerative Diseases","volume":"2015","author":"Prentice","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Xu, B., Chen, S., Luo, Y., Chen, Z., Liu, L., Zhou, H., Chen, W., Shen, T., Han, X., and Chen, L. (2011). Calcium signaling is involved in cadmium-induced neuronal apoptosis via induction of reactive oxygen species and activation of MAPK\/mTOR network. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019052"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/s41418-018-0171-y","article-title":"STAT3 localizes to the ER, acting as a gatekeeper for ER-mitochondrion Ca2+ fluxes and apoptotic responses","volume":"26","author":"Avalle","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/1873-3468.12902","article-title":"The role of mitochondrial ROS in the aging brain","volume":"592","author":"Stefanatos","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"117148","DOI":"10.1016\/j.lfs.2019.117148","article-title":"High glucose augments ROS generation regulates mitochondrial dysfunction and apoptosis via stress signalling cascades in keratinocytes","volume":"241","author":"Rizwan","year":"2020","journal-title":"Life Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"112388","DOI":"10.1016\/j.fct.2021.112388","article-title":"Mitophagy and apoptosis mediated by ROS participate in AlCl3-induced MC3T3-E1 cell dysfunction","volume":"155","author":"Liu","year":"2021","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1080\/14786419.2018.1509332","article-title":"Inhibitory effects of schisantherin F from Schisandra propinqua subsp. sinensis on human melanoma A375 cells through ROS-induced mitochondrial dysfunction and mitochondria-mediated apoptosis","volume":"34","author":"Gao","year":"2020","journal-title":"Nat. Product. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"118631","DOI":"10.1016\/j.lfs.2020.118631","article-title":"TMT-based proteomics analysis to screen potential biomarkers of acute-phase TBI in rats","volume":"264","author":"Wang","year":"2021","journal-title":"Life Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"153846","DOI":"10.1016\/j.phymed.2021.153846","article-title":"TMT-based proteomics analysis reveals the protective effect of Jueyin granules on imiquimod-induced psoriasis mouse model by causing autophagy","volume":"96","author":"Song","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"118020","DOI":"10.1016\/j.lfs.2020.118020","article-title":"The role of CREB and BDNF in neurobiology and treatment of Alzheimer\u2019s disease","volume":"257","author":"Amidfar","year":"2020","journal-title":"Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.2174\/1570159X17666190809165549","article-title":"Dietary Flavonoids Interaction with CREB-BDNF Pathway: An Unconventional Approach for Comprehensive Management of Epilepsy","volume":"17","author":"Sharma","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2174\/1570159X14666160119094646","article-title":"Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets","volume":"14","author":"Zhang","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.bbadis.2009.12.009","article-title":"Pathological roles of MAPK signaling pathways in human diseases","volume":"1802","author":"Kim","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_59","first-page":"554","article-title":"Auricular electroacupuncture improves depression possibly by promoting hippocampal Raf\/ERK\/RSK\/CREB signaling in chronic unpredictable mild stress induced depression rats","volume":"44","author":"Li","year":"2019","journal-title":"Acupunct. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2020.01.026","article-title":"Tanshinone IIA Improves Depression-like Behavior in Mice by Activating the ERK-CREB-BDNF Signaling Pathway","volume":"430","author":"Lu","year":"2020","journal-title":"Neuroscience"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"147261","DOI":"10.1016\/j.brainres.2020.147261","article-title":"Protriptyline improves spatial memory and reduces oxidative damage by regulating NF\u03baB-BDNF\/CREB signaling axis in streptozotocin-induced rat model of Alzheimer\u2019s disease","volume":"1754","author":"Tiwari","year":"2021","journal-title":"Brain Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101876","DOI":"10.1016\/j.gendis.2025.101876","article-title":"Non-canonical role of \"S6K1-SGK1\" pathway in neuronal necroptosis following traumatic brain injury","volume":"13","author":"Wang","year":"2025","journal-title":"Genes Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e70107","DOI":"10.1002\/mco2.70107","article-title":"Noncanonical feedback loop between \"RIP3-MLKL\" and \"4EBP1-eIF4E\" promotes neuronal necroptosis","volume":"6","author":"Wang","year":"2025","journal-title":"MedComm"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Li, Y.Z., Wu, Z.Y., Zhu, B.Q., Wang, Y.X., Kan, Y.Q., and Zeng, H.C. (2022). The BDNF-TrkB-CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation. Toxics, 10.","DOI":"10.3390\/toxics10080413"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.euroneuro.2017.03.005","article-title":"The involvement of BDNF-CREB signaling pathways in the pharmacological mechanism of combined SSRI- antipsychotic treatment in schizophrenia","volume":"27","author":"Einoch","year":"2017","journal-title":"Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jprot.2018.11.023","article-title":"Proteomic analysis of olfactory bulb suggests CACNA1E as a promoter of CREB signaling in microbiota-induced depression","volume":"194","author":"Huang","year":"2019","journal-title":"J. Proteom."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Chiu, C.H., Chyau, C.C., Chen, C.C., Lee, L.Y., Chen, W.P., Liu, J.L., Lin, W.H., and Mong, M.C. (2018). Erinacine A-Enriched Hericium erinaceus Mycelium Produces Antidepressant-Like Effects through Modulating BDNF\/PI3K\/Akt\/GSK-3\u03b2 Signaling in Mice. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020341"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.biopha.2017.10.090","article-title":"Corin protects H2O2-induced apoptosis through PI3K\/AKT and NF-\u03baB pathway in cardiomyocytes","volume":"97","author":"Li","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Li, S., Lu, C., Kang, L., Li, Q., Chen, H., Zhang, H., Tang, Z., Lin, Y., Bai, M., and Xiong, P. (2023). Study on correlations of BDNF, PI3K, AKT and CREB levels with depressive emotion and impulsive behaviors in drug-na\u00efve patients with first-episode schizophrenia. BMC Psychiatry, 23.","DOI":"10.1186\/s12888-023-04718-8"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1080\/13543784.2019.1676726","article-title":"Targeting AKT for cancer therapy","volume":"28","author":"Shariati","year":"2019","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1139\/O09-189","article-title":"Neuregulin-1 regulates the expression of Akt, Bcl-2, and Bad signaling after focal cerebral ischemia in rats","volume":"88","author":"Guo","year":"2010","journal-title":"Biochem. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Aniogo, E.C., George, B.P.A., and Abrahamse, H. (2020). Role of Bcl-2 Family Proteins in Photodynamic Therapy Mediated Cell Survival and Regulation. Molecules, 25.","DOI":"10.3390\/molecules25225308"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e12419","DOI":"10.1111\/jpi.12419","article-title":"Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3-dependent regulation of oxidative stress and apoptosis","volume":"63","author":"Zhai","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s12640-016-9611-y","article-title":"Baicalin Attenuates Ketamine-Induced Neurotoxicity in the Developing Rats: Involvement of PI3K\/Akt and CREB\/BDNF\/Bcl-2 Pathways","volume":"30","author":"Zuo","year":"2016","journal-title":"Neurotox. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5255","DOI":"10.1002\/ptr.70388","article-title":"Paeoniflorin Ameliorates Alcohol-Induced Depression via Modulating the Gut\u2013Brain Axis and Inhibiting the NF-\u03baB\/NLRP3 Inflammasome Pathway in Mice","volume":"40","author":"Yu","year":"2026","journal-title":"Phyther. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"D1211","DOI":"10.1093\/nar\/gky869","article-title":"iProX: An integrated proteome resource","volume":"47","author":"Ma","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"D1522","DOI":"10.1093\/nar\/gkab1081","article-title":"iProX in 2021: Connecting proteomics data sharing with big data","volume":"50","author":"Chen","year":"2021","journal-title":"Nucleic Acids Res."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/9\/944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:27:50Z","timestamp":1789705670000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/9\/944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":77,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cimb48090944"],"URL":"https:\/\/doi.org\/10.3390\/cimb48090944","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}