{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:17:28Z","timestamp":1790860648685,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Jilin Province, China","award":["20210101031JC"],"award-info":[{"award-number":["20210101031JC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The flowers of Pueraria lobate (Puerariae Flos) have served as a traditional Chinese medicinal and food herbage plant for many years. Tectoridin is one of the most active metabolites extracted from flowers of Pueraria lobate and has a variety of beneficial activities, including antioxidative, hypoglycemic, and anti-inflammatory activities. Nevertheless, the functions and potential mechanisms underlying tectoridin in cerebral ischemia\/reperfusion injury have not been well interpreted; thus, a network analysis strategy was performed to systematically evaluate its pharmacological mechanisms, which were further validated in rats with cerebral ischemia. Network analysis predicted that tectoridin could attenuate brain damage after stroke by modulating signaling pathways associated with redox, inflammation, and autophagy. The experimental results demonstrated an improvement in neurological function in rats treated with tectoridin, along with a significant reduction in cerebral infarction volume. The neuroprotective benefits of tectoridin stem, in part, from its antioxidant capabilities, which include the upregulation of Nrf2\/HO-1 protein expression, reduction of the TLR4\/MYD88\/NF-\u03baB inflammatory pathway, and inhibition of the PI3K\/Akt\/mTOR pathway, contributing to its anti-apoptotic effects. This investigation offers a thorough examination of the pathways and targets linked to the therapeutic effects of tectoridin on ischemic stroke, highlighting its anti-inflammatory, antioxidative, and anti-apoptotic mechanisms. These findings serve as a valuable reference for the development and exploration of effective anti-ischemic stroke medications.<\/jats:p>","DOI":"10.3390\/ijms26041402","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T05:04:33Z","timestamp":1738904673000},"page":"1402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Network Pharmacology Analysis and Experimental Validation of Tectoridin in the Treatment of Ischemic Stroke by Inhibiting Apoptosis and Regulating Inflammation"],"prefix":"10.3390","volume":"26","author":[{"given":"Tingting","family":"Lu","sequence":"first","affiliation":[{"name":"College of Life Sciences, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Xue","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Jin","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2629-7653","authenticated-orcid":false,"given":"Meizhu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Central Laboratory, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfang","family":"Shi","sequence":"additional","affiliation":[{"name":"Central Laboratory, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-6479","authenticated-orcid":false,"given":"Kai","family":"Song","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Changchun Normal University, Changchun 130032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1056\/NEJMoa052980","article-title":"NXY-059 for acute ischemic stroke","volume":"354","author":"Lees","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107848","DOI":"10.1016\/j.pharmthera.2021.107848","article-title":"Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics","volume":"225","author":"Ajoolabady","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0140-6736(97)03022-5","article-title":"Systematic review of evidence on thrombolytic therapy for acute ischaemic stroke","volume":"350","author":"Wardlaw","year":"1997","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"739","DOI":"10.2174\/138161206775474242","article-title":"Mitochondria: A target for neuroprotective interventions in cerebral ischemia-reperfusion","volume":"12","author":"Christophe","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"40","DOI":"10.17116\/jnevro202212206140","article-title":"Farmakoterapiya v postinsul\u2019tnoi reabilitatsii [Pharmacotherapy in post-stroke rehabilitation]","volume":"122","author":"Lyukmanov","year":"2022","journal-title":"S.S. Korsakov J. Neurol. Psychiatry"},{"key":"ref_6","first-page":"CD013306","article-title":"Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: A network meta-analysis","volume":"2021","author":"Battle","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jneuroim.2006.11.014","article-title":"The inflammatory response in stroke","volume":"184","author":"Wang","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"402","DOI":"10.4103\/0028-3886.28115","article-title":"Brain edema after intracerebral hemorrhage in rats: The role of inflammation","volume":"54","author":"Zhang","year":"2006","journal-title":"Neurol. India"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1126\/science.296.5573.1655","article-title":"The phosphoinositide 3-kinase pathway","volume":"296","author":"Cantley","year":"2002","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.brainresbull.2012.06.010","article-title":"Losartan, an angiotensin II type 1 receptor blocker, ameliorates cerebral ischemia-reperfusion injury via PI3K\/Akt-mediated eNOS phosphorylation","volume":"89","author":"Liu","year":"2012","journal-title":"Brain Res. Bull."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4312","DOI":"10.4049\/jimmunol.1600103","article-title":"GATA1-Deficient Dendritic Cells Display Impaired CCL21-Dependent Migration toward Lymph Nodes Due to Reduced Levels of Polysialic Acid","volume":"197","author":"Scheenstra","year":"2016","journal-title":"J. Immunol."},{"key":"ref_12","first-page":"1","article-title":"Geraniin Protects against Cerebral Ischemia\/Reperfusion Injury by Suppressing Oxidative Stress and Neuronal Apoptosis via Regulation of the Nrf2\/HO-1 Pathway","volume":"2022","author":"Yang","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_13","first-page":"1","article-title":"Fucoxanthin Attenuates Oxidative Damage by Activating the Sirt1\/Nrf2\/HO-1 Signaling Pathway to Protect the Kidney from Ischemia-Reperfusion Injury","volume":"2022","author":"Mao","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.7314\/APJCP.2014.15.5.2329","article-title":"Curcumin inhibits MHCC97H liver cancer cells by activating ROS\/TLR-4\/caspase signaling pathway","volume":"15","author":"Li","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, Y., Deng, S.-L., Lian, Z.-X., and Yu, K. (2019). Roles of Toll-Like Receptors in Nitroxidative Stress in Mammals. Cells, 8.","DOI":"10.3390\/cells8060576"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jss.2020.11.041","article-title":"Dexmedetomidine Resists Intestinal Ischemia-Reperfusion Injury by Inhibiting TLR4\/MyD88\/NF-\u03baB Signaling","volume":"260","author":"Yang","year":"2021","journal-title":"J. Surg. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, N., Guo, W., Liu, T., Chen, X., and Lin, M. (2023). Toll-like receptors (TLR2 and TLR4) antagonist mitigates the onset of cerebral small vessel disease through PI3K\/Akt\/GSK3\u03b2 pathway in stroke-prone renovascular hypertensive rats. Biotechnol. Genet. Eng. Rev., 40.","DOI":"10.1080\/02648725.2023.2184961"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.lfs.2017.10.035","article-title":"Improvement in cerebral ischemia\u2013reperfusion injury through the TLR4\/NF-\u03baB pathway after Kudiezi injection in rats","volume":"191","author":"Liu","year":"2017","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.phrs.2015.08.025","article-title":"Dioscin attenuates renal ischemia\/reperfusion injury by inhibiting the TLR4\/MyD88 signaling pathway via up-regulation of HSP70","volume":"100","author":"Qi","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tao, X., Sun, X., Xu, L., Yin, L., Han, X., Qi, Y., Xu, Y., Zhao, Y., Wang, C., and Peng, J. (2016). Total Flavonoids from Rosa laevigata Michx Fruit Ameliorates Hepatic Ischemia\/Reperfusion Injury through Inhibition of Oxidative Stress and Inflammation in Rats. Nutrients, 8.","DOI":"10.3390\/nu8070418"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhou, H., Zhang, M., Cao, H., Du, X., Zhang, X., Wang, J., and Bi, X. (2023). Research Progress on the Synergistic Anti-Tumor Effect of Natural Anti-Tumor Components of Chinese Herbal Medicine Combined with Chemotherapy Drugs. Pharmaceuticals, 16.","DOI":"10.3390\/ph16121734"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Luo, L., Zhong, A., Wang, Q., and Zheng, T. (2021). Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, ADMET, and Molecular Dynamics (MD) Simulation of Potential Inhibitors of PD-L1 from the Library of Marine Natural Products. Mar. Drugs, 20.","DOI":"10.3390\/md20010029"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Shikov, A.N., Flisyuk, E.V., Obluchinskaya, E.D., and Pozharitskaya, O.N. (2020). Pharmacokinetics of Marine-Derived Drugs. Mar. Drugs, 18.","DOI":"10.3390\/md18110557"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_25","first-page":"1254","article-title":"A study to evaluate the quality of reports on systematic evaluation\/meta-analysis of intervention classes published in the Chinese Journal of Traditional Chinese Medicine","volume":"43","author":"Zhang","year":"2018","journal-title":"China J. Chin. Mater. Medica"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.fct.2011.10.066","article-title":"In vitro evaluation of tectoridin, tectorigenin and tectorigenin sodium sulfonate on antioxidant properties","volume":"50","author":"Han","year":"2012","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_27","first-page":"4431","article-title":"Tectorigenin attenuates the MPP+-induced SH-SY5Y cell damage, indicating a potential beneficial role in Parkinson\u2019s disease by oxidative stress inhibition","volume":"14","author":"Gong","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/BF02980104","article-title":"Antioxidant activities of isoflavones from the rhizomes ofbelamcanda chinensis on carbon tetrachloride-lnduced hepatic injury in rats","volume":"27","author":"Jung","year":"2004","journal-title":"Arch. Pharmacal Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/BF02976573","article-title":"Hypoglycemic and hypolipidemic effects of tectorigenin and kaikasaponin III in the streptozotocin-induced diabetic rat and their antioxidant activity in vitro","volume":"23","author":"Lee","year":"2000","journal-title":"Arch. Pharmacal Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1124\/jpet.106.114322","article-title":"Anti-Inflammatory Mechanisms of Isoflavone Metabolites in Lipopolysaccharide-Stimulated Microglial Cells","volume":"320","author":"Park","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.fitote.2014.09.009","article-title":"Excretion of tectoridin metabolites in rat urine and bile orally administrated at different dosages and their inhibitory activity against aldose reductase","volume":"99","author":"Qu","year":"2014","journal-title":"Fitoterapia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s11845-015-1371-9","article-title":"Edaravone offers neuroprotection for acute diabetic stroke patients","volume":"185","author":"Zheng","year":"2016","journal-title":"Ir. J. Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1166\/jnn.2021.18668","article-title":"Influence of Nanoparticle-Loaded Edaravone on Postoperative Effects in Patients with Cerebral Hemorrhage","volume":"21","author":"Dang","year":"2021","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chen, Q., Cai, Y., Zhu, X., Wang, J., Gao, F., Yang, M., Mao, L., Zhang, Z., and Sun, B. (2022). Edaravone Dexborneol Treatment Attenuates Neuronal Apoptosis and Improves Neurological Function by Suppressing 4-HNE-Associated Oxidative Stress After Subarachnoid Hemorrhage. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.848529"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1001\/jamaneurol.2021.4893","article-title":"Safety and Effectiveness of Long-term Intravenous Administration of Edaravone for Treatment of Patients With Amyotrophic Lateral Sclerosis","volume":"79","author":"Witzel","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"115876","DOI":"10.1016\/j.jep.2022.115876","article-title":"Mechanism of Sijunzi Decoction in the treatment of colorectal cancer based on network pharmacology and experimental validation","volume":"302","author":"Shang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"116306","DOI":"10.1016\/j.jep.2023.116306","article-title":"Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula","volume":"309","author":"Zhao","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_38","first-page":"2443615","article-title":"Exploring Active Compounds and Mechanisms of Angong Niuhuang Wan on Ischemic Stroke Based on Network Pharmacology and Molecular Docking","volume":"2022","author":"Zhang","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med. Ecam"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Sun, Z., Wang, Y., Pang, X., Wang, X., and Zeng, H. (2023). Mechanisms of polydatin against spinal cord ischemia\u2013reperfusion injury based on network pharmacology, molecular docking and molecular dynamics simulation. Bioorganic Chem., 140.","DOI":"10.1016\/j.bioorg.2023.106840"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e34945","DOI":"10.1097\/MD.0000000000034945","article-title":"Predicting the anti-inflammatory mechanism of Radix Astragali using network pharmacology and molecular docking","volume":"102","author":"Ren","year":"2023","journal-title":"Medicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1007\/s11596-024-2858-2","article-title":"Crosstalk among Oxidative Stress, Autophagy, and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells: A Mixed Computational and Experimental Study","volume":"44","author":"Luo","year":"2024","journal-title":"Curr. Med. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18341","DOI":"10.1021\/acsomega.4c00200","article-title":"Investigating the Mechanistic of Danhong Injection in Brain Damage Caused by Cardiac I\/R Injury via Bioinformatics, Computer Simulation, and Experimental Validation","volume":"9","author":"Wang","year":"2024","journal-title":"ACS Omega"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15293","DOI":"10.1007\/s00432-023-05277-x","article-title":"Inhibitors of the PI3K\/AKT\/mTOR pathway in human malignancies; trend of current clinical trials","volume":"149","author":"Delshad","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.gendis.2018.06.001","article-title":"Resveratrol provides neuroprotection by regulating the JAK2\/STAT3\/PI3K\/AKT\/mTOR pathway after stroke in rats","volume":"5","author":"Hou","year":"2018","journal-title":"Genes Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s11064-017-2202-3","article-title":"\u03b2-Caryophyllene Pretreatment Alleviates Focal Cerebral Ischemia-Reperfusion Injury by Activating PI3K\/Akt Signaling Pathway","volume":"42","author":"Zhang","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.neulet.2012.08.078","article-title":"Protection by silibinin against experimental ischemic stroke: Up-regulated pAkt, pmTOR, HIF-1\u03b1 and Bcl-2, down-regulated Bax, NF-\u03baB expression","volume":"529","author":"Wang","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zheng, M., Zhou, M., Chen, M., Lu, Y., Shi, D., Wang, J., and Liu, C. (2022). Neuroprotective Effect of Daidzein Extracted From Pueraria lobate Radix in a Stroke Model Via the Akt\/mTOR\/BDNF Channel. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.772485"},{"key":"ref_48","first-page":"154644","article-title":"Gomisin N attenuated cerebral ischemia-reperfusion injury through inhibition of autophagy by activating the PI3K\/AKT\/mTOR pathway","volume":"110","author":"Li","year":"2023","journal-title":"Phytomedicine Int. J. Phytother. Phytopharm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s12031-024-02197-4","article-title":"MRPS9-Mediated Regulation of the PI3K\/Akt\/mTOR Pathway Inhibits Neuron Apoptosis and Protects Ischemic Stroke","volume":"74","author":"Jiang","year":"2024","journal-title":"J. Mol. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1161\/01.STR.0000143454.14159.28","article-title":"Modification of endothelial no synthase through protein phosphorylation after forebrain cerebral ischemia\/reperfusion","volume":"35","author":"Osuka","year":"2004","journal-title":"Stroke"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1097\/00004647-200112000-00009","article-title":"Evidence of phosphorylation of Akt and neuronal survival after transient focal cerebral ischemia in mice","volume":"21","author":"Noshita","year":"2001","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0006-8993(02)02474-5","article-title":"Upregulation of Akt phosphorylation at the early stage of middle cerebral artery occlusion in mice","volume":"942","author":"Shibata","year":"2002","journal-title":"Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/j.1471-4159.2008.05218.x","article-title":"The Akt signaling pathway contributes to postconditioning\u2019s protection against stroke; the protection is associated with the MAPK and PKC pathways","volume":"105","author":"Gao","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.neuroscience.2012.03.008","article-title":"Progesterone is neuroprotective against ischemic brain injury through its effects on the phosphoinositide 3-kinase\/protein kinase B signaling pathway","volume":"210","author":"Ishrat","year":"2012","journal-title":"Neuroscience"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wang, C., Chen, H., Jiang, H.-H., Mao, B.-B., and Yu, H. (2021). Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.772401"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3892\/etm.2022.11362","article-title":"Elucidation of the mechanism of miR-122-5p in mediating FOXO3 injury and apoptosis of mouse cochlear hair cells induced by hydrogen peroxide","volume":"23","author":"Chen","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"101085","DOI":"10.1016\/j.mam.2022.101085","article-title":"Caspase mechanisms in the regulation of inflammation","volume":"88","author":"Salvesen","year":"2022","journal-title":"Mol. Asp. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1159\/000374076","article-title":"Tetramethylpyrazine Ameliorated Hypoxia-Induced Myocardial Cell Apoptosis via HIF-1\u03b1\/JNK\/p38 and IGFBP3\/BNIP3 Inhibition to Upregulate PI3K\/Akt Survival Signaling","volume":"36","author":"Lin","year":"2015","journal-title":"Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jep.2016.01.028","article-title":"PI3K\/Akt pathway contributes to neuroprotective effect of Tongxinluo against focal cerebral ischemia and reperfusion injury in rats","volume":"181","author":"Yu","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1177\/1758834014530023","article-title":"The PI3K\/AKT\/mTOR pathway in breast cancer: Targets, trials and biomarkers","volume":"6","author":"Paplomata","year":"2014","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ctrv.2017.07.005","article-title":"Phosphoinositide 3-kinase (PI3K) pathway inhibitors in solid tumors: From laboratory to patients","volume":"59","author":"Janku","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Farina, M., Vieira, L.E., Buttari, B., Profumo, E., and Saso, L. (2021). The Nrf2 Pathway in Ischemic Stroke: A Review. Molecules, 26.","DOI":"10.3390\/molecules26165001"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Sun, Y.-Y., Zhu, H.-J., Zhao, R.-Y., Zhou, S.-Y., Wang, M.-Q., Yang, Y., and Guo, Z.-N. (2023). Remote ischemic conditioning attenuates oxidative stress and inflammation via the Nrf2\/HO-1 pathway in MCAO mice. Redox Biol., 66.","DOI":"10.1016\/j.redox.2023.102852"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"114655","DOI":"10.1016\/j.expneurol.2023.114655","article-title":"Crosstalk between Nrf2 signaling pathway and inflammation in ischemic stroke: Mechanisms of action and therapeutic implications","volume":"373","author":"Tameh","year":"2024","journal-title":"Exp. Neurol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Morsy, M.A., Abdel-Gaber, S.A., Rifaai, R.A., Mohammed, M.M., Nair, A.B., and Abdelzaher, W.Y. (2022). Protective mechanisms of telmisartan against hepatic ischemia\/reperfusion injury in rats may involve PPAR\u03b3-induced TLR4\/NF-\u03baB suppression. Biomed. Pharmacother., 145.","DOI":"10.1016\/j.biopha.2021.112374"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.toxrep.2019.07.010","article-title":"Renal and testicular up-regulation of pro-inflammatory chemokines (RANTES and CCL2) and cytokines (TNF-\u03b1, IL-1\u03b2, IL-6) following acute edible camphor administration is through activation of NF-kB in rats","volume":"6","author":"Somade","year":"2019","journal-title":"Toxicol. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.2174\/0113816128300103240529114808","article-title":"Hua-Feng-Dan alleviates LPS-induced neuroinflammation by inhibiting the TLR4\/Myd88\/NF-\u03baB pathway: Through Integrating Network Pharmacology and Experimental Validation","volume":"30","author":"Zhang","year":"2024","journal-title":"Curr. Pharm. Des."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/08923973.2022.2073890","article-title":"Tectoridin alleviates lipopolysaccharide-induced inflammation via inhibiting TLR4-NF-\u03baB\/NLRP3 signaling in vivo and in vitro","volume":"44","author":"Niu","year":"2022","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"D1373","DOI":"10.1093\/nar\/gkac956","article-title":"PubChem 2023 update","volume":"51","author":"Kim","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Daina, A., Michielin, O., and Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 7.","DOI":"10.1038\/srep42717"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"W356","DOI":"10.1093\/nar\/gkx374","article-title":"PharmMapper 2017 update: A web server for potential drug target identification with a comprehensive target pharmacophore database","volume":"45","author":"Wang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Fishilevich, S., Nudel, R., Rappaport, N., Hadar, R., Plaschkes, I., Stein, T.I., Rosen, N., Kohn, A., Twik, M., and Safran, M. (2017). GeneHancer: Genome-wide integration of enhancers and target genes in GeneCards. Database J. Biol. Databases Curation, 2017.","DOI":"10.1093\/database\/bax028"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"D789","DOI":"10.1093\/nar\/gku1205","article-title":"OMIM.org: Online Mendelian Inheritance in Man (OMIM\u00ae), an online catalog of human genes and genetic disorders","volume":"43","author":"Amberger","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/cpt.2350","article-title":"An Evidence-Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine","volume":"110","author":"Huddart","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_75","first-page":"D845","article-title":"The DisGeNET knowledge platform for disease genomics: 2019 update","volume":"48","author":"Ronzano","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"W169","DOI":"10.1093\/nar\/gkm415","article-title":"DAVID Bioinformatics Resources: Expanded annotation database and novel algorithms to better extract biology from large gene lists","volume":"35","author":"Huang","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0006-8993(99)01528-0","article-title":"Middle cerebral artery occlusion in the mouse by intraluminal suture coated with poly-L-lysine: Neurological and histological validation","volume":"833","author":"Belayev","year":"1999","journal-title":"Brain Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1161\/01.STR.20.1.84","article-title":"Reversible middle cerebral artery occlusion without craniectomy in rats","volume":"20","author":"Longa","year":"1989","journal-title":"Stroke"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/4\/1402\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:28:38Z","timestamp":1760027318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/4\/1402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,7]]},"references-count":80,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26041402"],"URL":"https:\/\/doi.org\/10.3390\/ijms26041402","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,7]]}}}