{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:55:13Z","timestamp":1790769313252,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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":"publisher","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":"publisher"}]},{"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":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Gastrodin (GAS), a bioactive glycoside from Gastrodia elata, shows anti-inflammatory and neuroprotective activity in preclinical models. This narrative review evaluates whether autophagy, mitochondrial quality control, and NOD-like receptor family pyrin domain containing 3 (NLRP3)-dependent pyroptosis may contribute to its effects on microglia. Studies in microglial cultures and animal models report reduced inflammatory activation and changes in microglial phenotype after GAS treatment. Related studies in endothelial cells, neurons, macrophages, and whole brain tissue associate GAS with AMP-activated protein kinase (AMPK) signaling, mechanistic target of rapamycin (mTOR) inhibition, autophagy or mitophagy markers, and lower inflammasome or pyroptosis markers. These findings support an AMPK\/mTOR\/NLRP3-centered working model, but the complete causal chain has not been demonstrated in microglia within a single experimental system. We distinguish microglia-specific observations from evidence extrapolated across cell types and disease models, compare GAS with its metabolite p-hydroxybenzyl alcohol, and discuss limitations of inhibitor-based experiments and variation in dose and sampling time. Inducible microglial genetic deletion, flux measurements, target-engagement assays, and matched pharmacokinetic studies are needed to test this model. Human evidence remains insufficient to confirm the proposed microglial mechanism or its clinical relevance.<\/jats:p>","DOI":"10.3390\/ijms27198754","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:59:25Z","timestamp":1790765965000},"page":"8754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gastrodin and Microglial Autophagy\u2013Pyroptosis Crosstalk: Evidence and Hypotheses Involving the AMPK\/mTOR\/NLRP3 Axis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5702-5730","authenticated-orcid":false,"given":"Chan-Yen","family":"Kuo","sequence":"first","affiliation":[{"name":"Institute of Oral Medicine and Materials, College of Medicine, Tzu Chi University, Hualien 97004, 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":[[2026,9,30]]},"reference":[{"key":"ref_1","first-page":"1229","article-title":"Microglia mediated neuroinflammation\u2014Signaling regulation and therapeutic considerations with special reference to some natural compounds","volume":"35","author":"Yao","year":"2020","journal-title":"Histol. Histopathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.brainres.2019.04.025","article-title":"Gastrodin attenuates proliferation and inflammatory responses in activated microglia through Wnt\/beta-catenin signaling pathway","volume":"1717","author":"Yao","year":"2019","journal-title":"Brain Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.31083\/j.jin2102072","article-title":"Gastrodin suppresses pyroptosis and exerts neuroprotective effect in traumatic brain injury model by inhibiting NLRP3 inflammasome signaling pathway","volume":"21","author":"Yang","year":"2022","journal-title":"J. Integr. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155518","DOI":"10.1016\/j.phymed.2024.155518","article-title":"Gastrodin regulates the TLR4\/TRAF6\/NF-kappaB pathway to reduce neuroinflammation and microglial activation in an AD model","volume":"128","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"154725","DOI":"10.1016\/j.phymed.2023.154725","article-title":"Gastrodin programs an Arg-1(+) microglial phenotype in hippocampus to ameliorate depression- and anxiety-like behaviors via the Nrf2 pathway in mice","volume":"113","author":"Zhang","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e70811","DOI":"10.1002\/cns.70811","article-title":"The Dual Role of Gastrodin in Spinal Cord Injury: Microglial Phenotype Switching and Neuronal Survival via PI3K\/AKT Activation","volume":"32","author":"Feng","year":"2026","journal-title":"CNS Neurosci. Ther."},{"key":"ref_7","first-page":"325","article-title":"Gastrodin inhibits neuroinflammation in rotenone-induced Parkinson\u2019s disease model rats","volume":"7","author":"Li","year":"2012","journal-title":"Neural Regen. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1142\/S0192415X26500199","article-title":"Gastrodin and Gastrodigenin as Potential Neuroprotectors for the Treatment of Neurodegenerative Diseases","volume":"54","author":"Wang","year":"2026","journal-title":"Am. J. Chin. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dai, J.N., Zong, Y., Zhong, L.M., Li, Y.M., Zhang, W., Bian, L.G., Ai, Q.L., Liu, Y.D., Sun, J., and Lu, D. (2011). Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021891"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s13105-019-00702-7","article-title":"Gastrodin ameliorates microvascular reperfusion injury-induced pyroptosis by regulating the NLRP3\/caspase-1 pathway","volume":"75","author":"Sun","year":"2019","journal-title":"J. Physiol. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zheng, X., Gong, T., Tang, C., Zhong, Y., Shi, L., Fang, X., Chen, D., and Zhu, Z. (2022). Gastrodin improves neuroinflammation-induced cognitive dysfunction in rats by regulating NLRP3 inflammasome. BMC Anesthesiol., 22.","DOI":"10.1186\/s12871-022-01915-y"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cai, A., Li, Z., Liu, R., Huang, H., Liu, P., Zhang, R., Xiao, J., Lin, Y., Hu, Q., and Wu, H. (2026). Gastrodin alleviates neuronal damage in epileptic cell models by targeting P2RY12 to inhibit microglial hyperactivation. PLoS ONE, 21.","DOI":"10.1371\/journal.pone.0346877"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121920","DOI":"10.1016\/j.jep.2026.121920","article-title":"Uncovering the quality markers and mechanisms of Gastrodia elata against LPS-induced neuroinflammation via network pharmacology and experimental verification","volume":"369","author":"Chen","year":"2026","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"106627","DOI":"10.1016\/j.intimp.2020.106627","article-title":"The improvement effect of gastrodin on LPS\/GalN-induced fulminant hepatitis via inhibiting inflammation and apoptosis and restoring autophagy","volume":"85","author":"Lv","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5769","DOI":"10.1111\/jcmm.16600","article-title":"Gastrodin induces lysosomal biogenesis and autophagy to prevent the formation of foam cells via AMPK-FoxO1-TFEB signalling axis","volume":"25","author":"Tao","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.bbrc.2023.06.011","article-title":"Gastrodin relieves cognitive impairment by regulating autophagy via PI3K\/AKT signaling pathway in vascular dementia","volume":"671","author":"Chen","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1007\/s11064-021-03285-2","article-title":"Gastrodin Alleviates Cerebral Ischaemia\/Reperfusion Injury by Inhibiting Pyroptosis by Regulating the lncRNA NEAT1\/miR-22-3p Axis","volume":"46","author":"Zhang","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s12012-026-10139-2","article-title":"Gastrodin Ameliorates Blood Pressure by Targeting the PPAR-gamma\/NF-kappaB\/NLRP3 Signaling Axis in the Hypothalamic Paraventricular Nucleus","volume":"26","author":"Yang","year":"2026","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e70559","DOI":"10.1111\/cns.70559","article-title":"Gastrodin Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Mitochondrial Fusion and Activating the AMPK-OPA1 Signaling Pathway","volume":"31","author":"Liu","year":"2025","journal-title":"CNS Neurosci. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"155900","DOI":"10.1016\/j.phymed.2024.155900","article-title":"Gastrodin exerts perioperative myocardial protection by improving mitophagy through the PINK1\/Parkin pathway to reduce myocardial ischemia-reperfusion injury","volume":"133","author":"Chen","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_21","first-page":"607","article-title":"FAP-targeted gastrodin nanoparticles in responsive hydrogel alleviate cardiac fibrosis via fibroblast metabolic reprogramming","volume":"62","author":"Jiang","year":"2026","journal-title":"Bioact. Mater."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhao, S., Li, X., Wang, J., and Wang, H. (2021). The Role of the Effects of Autophagy on NLRP3 Inflammasome in Inflammatory Nervous System Diseases. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.657478"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lu, R., Zhang, L., and Yang, X. (2022). Interaction between autophagy and the NLRP3 inflammasome in Alzheimer\u2019s and Parkinson\u2019s disease. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.1018848"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Liu, Y., Gao, J., Peng, M., Meng, H., Ma, H., Cai, P., Xu, Y., Zhao, Q., and Si, G. (2018). A Review on Central Nervous System Effects of Gastrodin. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00024"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1007\/s00210-023-02920-9","article-title":"Gastrodin: A comprehensive pharmacological review","volume":"397","author":"Wang","year":"2024","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"155369","DOI":"10.1016\/j.phymed.2024.155369","article-title":"Gastrodin alleviates mitochondrial dysfunction by regulating SIRT3-mediated TFAM acetylation in vascular dementia","volume":"128","author":"Chen","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ye, T., Meng, X., Wang, R., Zhang, C., He, S., Sun, G., and Sun, X. (2018). Gastrodin Alleviates Cognitive Dysfunction and Depressive-Like Behaviors by Inhibiting ER Stress and NLRP3 Inflammasome Activation in db\/db Mice. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123977"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/ibra.12118","article-title":"Pharmacological effects of gastrodin: Insight into neurological diseases and mechanism in ferroptosis and pyroptosis","volume":"11","author":"Zheng","year":"2025","journal-title":"Ibrain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"246","DOI":"10.3344\/kjp.25341","article-title":"Gastrodin alleviates bortezomib-induced peripheral neuropathy by inhibiting NF-kappaB\/NLRP3 pathway-mediated microglial inflammation","volume":"39","author":"Gu","year":"2026","journal-title":"Korean J. Pain."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"116266","DOI":"10.1016\/j.jpba.2024.116266","article-title":"Identification of key anti-neuroinflammatory components in Gastrodiae Rhizoma based on spectrum-effect relationships and its mechanism exploration","volume":"248","author":"Ma","year":"2024","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"150516","DOI":"10.1016\/j.brainres.2026.150516","article-title":"Gastrodin activates the AMPK signaling pathway by inhibiting PRMT1 to alleviate cerebral ischemia-reperfusion injury","volume":"1891","author":"Luo","year":"2026","journal-title":"Brain Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s10735-024-10273-7","article-title":"Gastrodin ameliorates diabetic nephropathy by activating the AMPK\/Nrf2 pathway","volume":"55","author":"Zhao","year":"2024","journal-title":"J. Mol. Histol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yao, M., Zhang, S., Wu, Y., Huang, Y., Song, Y., Wang, L., Li, S., Jia, L., Yao, B., and Li, B. (2026). Gastrodin alleviates cardiomyocyte senescence by regulating autophagy through the AMPK\/mTOR\/4EBP1 pathway. Front. Pharmacol., 17.","DOI":"10.3389\/fphar.2026.1851573"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1002\/ptr.8461","article-title":"Gastrodin Ameliorates Tau Pathology and BBB Dysfunction in 3xTg-AD Transgenic Mice by Regulating the ADRA1\/NF-kappaB\/NLRP3 Pathway to Reduce Neuroinflammation","volume":"39","author":"Li","year":"2025","journal-title":"Phytother. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105839","DOI":"10.1016\/j.ejps.2021.105839","article-title":"Comparative study on the intestinal absorption of three gastrodin analogues via the glucose transport pathway","volume":"163","author":"Guo","year":"2021","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1097\/WNR.0000000000001942","article-title":"Gastrodin facilitates recovery of neurological function of MCAO rats through upregulating miR-20a-5p\/XIAP pathway via exosome","volume":"34","author":"Nan","year":"2023","journal-title":"Neuroreport"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1097\/SHK.0000000000002542","article-title":"Gastrodin Protects against Sepsis-Associated Encephalopathy by Suppressing Ferroptosis","volume":"63","author":"Xu","year":"2025","journal-title":"Shock"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e70283","DOI":"10.1111\/cns.70283","article-title":"Gastrodin Alleviates Tau Pathology by Targeting the Alzheimer\u2019s Risk Gene FERMT2, Reversing the Reduction in Brain Viscoelasticity","volume":"31","author":"Wang","year":"2025","journal-title":"CNS Neurosci. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wu, S., Huang, R., Zhang, R., Xiao, C., Wang, L., Luo, M., Song, N., Zhang, J., Yang, F., and Liu, X. (2023). Gastrodin and Gastrodigenin Improve Energy Metabolism Disorders and Mitochondrial Dysfunction to Antagonize Vascular Dementia. Molecules, 28.","DOI":"10.3390\/molecules28062598"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.chroma.2014.06.080","article-title":"Identification and analysis of gastrodin and its five metabolites using ultra fast liquid chromatography electrospray ionization tandem mass spectrometry to investigate influence of multiple-dose and food","volume":"1358","author":"Jia","year":"2014","journal-title":"J. Chromatogr. A"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"157177","DOI":"10.1016\/j.phymed.2025.157177","article-title":"Gastrodin promotes Alkbh5 nuclear localization and Gclm m(6)A demethylation to alleviate ferroptosis in ischemic stroke","volume":"147","author":"Shi","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"155819","DOI":"10.1016\/j.phymed.2024.155819","article-title":"Gastrodin relieves Parkinson\u2019s disease-related motor deficits by facilitating the MEK-dependent VMAT2 to maintain dopamine homeostasis","volume":"132","author":"Zhao","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e73753","DOI":"10.7554\/eLife.73753","article-title":"Glial Nrf2 signaling mediates the neuroprotection exerted by Gastrodia elata Blume in Lrrk2-G2019S Parkinson\u2019s disease","volume":"10","author":"Lin","year":"2021","journal-title":"eLife"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1016\/j.jchromb.2010.05.034","article-title":"Determination and pharmacokinetics of gastrodin in human plasma by HPLC coupled with photodiode array detector","volume":"878","author":"Ju","year":"2010","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ijpharm.2007.03.041","article-title":"Pharmacokinetics of gastrodin in rat plasma and CSF after i.n. and i.v","volume":"341","author":"Wang","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.aca.2007.03.035","article-title":"Analysis of brain distribution and biliary excretion of a nutrient supplement, gastrodin, in rat","volume":"590","author":"Lin","year":"2007","journal-title":"Anal. Chim. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jpba.2007.10.017","article-title":"Distribution and metabolism of gastrodin in rat brain","volume":"46","author":"Wang","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.jpba.2008.07.013","article-title":"Pharmacokinetics of gastrodin and its metabolite p-hydroxybenzyl alcohol in rat blood, brain and bile by microdialysis coupled to LC-MS\/MS","volume":"48","author":"Lin","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Nepal, M.R., Jeong, K.S., Kim, G.H., Cha, D.H., Kang, M.J., Kim, J.S., Kim, J.H., and Jeong, T.C. (2019). Role of intestinal microbiota in metabolism of gastrodin in vitro and in vivo. Metabolites, 9.","DOI":"10.3390\/metabo9040069"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"123000","DOI":"10.1016\/j.ijpharm.2023.123000","article-title":"Strain differences in the drug transport capacity of intestinal glucose transporters in Sprague-Dawley versus Wistar rats, C57BL\/6J versus Kunming mice","volume":"640","author":"Huang","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3074","DOI":"10.1002\/hep.32068","article-title":"Gastrodin Improves Nonalcoholic Fatty Liver Disease Through Activation of the Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway","volume":"74","author":"Wan","year":"2021","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20070797","article-title":"The selectivity of protein kinase inhibitors: A further update","volume":"408","author":"Bain","year":"2007","journal-title":"Biochem. J."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sun, H., Li, M., Li, Y., Zheng, N., Li, J., Li, X., Liu, Y., Ji, Q., Zhou, L., and Su, J. (2024). Gastrodin Improves the Activity of the Ubiquitin-Proteasome System and the Autophagy-Lysosome Pathway to Degrade Mutant Huntingtin. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147709"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6611668","DOI":"10.1155\/2021\/6611668","article-title":"Gastrodin Promotes the Survival of Random-Pattern Skin Flaps via Autophagy Flux Stimulation","volume":"2021","author":"Chen","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)","volume":"17","author":"Klionsky","year":"2021","journal-title":"Autophagy"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"10850","DOI":"10.1074\/jbc.M109.080796","article-title":"Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase","volume":"285","author":"Wu","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1007\/s12017-020-08627-x","article-title":"Gastrodin Regulates the Notch Signaling Pathway and Sirt3 in Activated Microglia in Cerebral Hypoxic-Ischemia Neonatal Rats and in Activated BV-2 Microglia","volume":"23","author":"Guo","year":"2021","journal-title":"Neuromolecular Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3892\/etm.2021.11091","article-title":"Gastrodin inhibits high glucose-induced inflammation, oxidative stress and apoptosis in podocytes by activating the AMPK\/Nrf2 signaling pathway","volume":"23","author":"Huang","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s12017-019-08544-8","article-title":"Gastrodin Inhibits Inflammasome Through the STAT3 Signal Pathways in TNA2 Astrocytes and Reactive Astrocytes in Experimentally Induced Cerebral Ischemia in Rats","volume":"21","author":"Sui","year":"2019","journal-title":"Neuromolecular Med."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Jin, J., Kang, D.H., Lee, G.H., Kim, W.M., and Choi, J.I. (2024). Intrathecal gastrodin alleviates allodynia in a rat spinal nerve ligation model through NLRP3 inflammasome inhibition. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-024-04519-w"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Dong, Z., Yang, L., Jiao, J., Jiang, Y., Li, H., Yin, G., Yang, P., and Sun, L. (2022). Aspirin in combination with gastrodin protects cardiac function and mitigates gastric mucosal injury in response to myocardial ischemia\/reperfusion. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.995102"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s11626-021-00593-3","article-title":"Gastrodin alleviates inflammatory injury of cardiomyocytes in septic shock mice via inhibiting NLRP3 expression","volume":"57","author":"Shao","year":"2021","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17161","DOI":"10.1007\/s00210-025-04348-9","article-title":"Gastrodin inhibits hexokinase-2 mediated glycolysis to rescue rotenone-damaged PC12 cells","volume":"398","author":"Chen","year":"2025","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wang, S., Wu, J., Du, Q., Yu, H., Yang, L., Liu, X., Xu, K., Wang, C., and Feng, F. (2025). Gastrodin mitigates aortic valve calcification by inhibiting glycolysis and histone lactylation through interfering with valve interstitial cells. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1547716"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1111\/ejn.16371","article-title":"Gastrodin regulates the expression of renin-angiotensin system-SIRT3 and proinflammatory mediators in reactive astrocytes via activated microglia","volume":"60","author":"Zuo","year":"2024","journal-title":"Eur. J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1007\/s10787-018-0470-4","article-title":"Gastrodin microinjection suppresses 6-OHDA-induced motor impairments in parkinsonian rats: Insights into oxidative balance and microglial activation in SNc","volume":"26","author":"Haddadi","year":"2018","journal-title":"Inflammopharmacology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8657","DOI":"10.18632\/aging.205831","article-title":"Gastrodin ameliorates neuroinflammation in Alzheimer\u2019s disease mice by inhibiting NF-kappaB signaling activation via PPARgamma stimulation","volume":"16","author":"Yin","year":"2024","journal-title":"Aging"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1007\/s12035-026-05677-3","article-title":"Gastrodin Ameliorates Pain-Depression Comorbidity through SIRT3-Dependent Alleviation of Oxidative Stress and Promotion of Mitochondrial Biogenesis","volume":"63","author":"Zhou","year":"2026","journal-title":"Mol. Neurobiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"157705","DOI":"10.1016\/j.phymed.2025.157705","article-title":"Unraveling the neuroprotective mechanism of gastrodin against CRS-induced depression in adult male mice via Notch3: Integration of proteomics, transcriptomics, molecular docking, and cellular validation","volume":"150","author":"Xiang","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_70","first-page":"989","article-title":"The role and mechanism of gastrodin in the medial prefrontal cortex autophagy of PTSD rats","volume":"13","author":"Lei","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Dai, Y., Wang, S., Luo, J., Yu, H., Du, Q., Hou, S., Liu, M., Jiang, S., Xu, H., and Ye, S. (2025). Gastrodin attenuates rheumatoid arthritis by targeting KAT8 to inhibit the lactylation of H3K9. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1559744"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13054-025-05331-9","article-title":"Efficacy and safety of gastrodin in preventing postoperative delirium following cardiac surgery: A randomized placebo controlled clinical trial","volume":"29","author":"Bai","year":"2025","journal-title":"Crit. Care"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kong, F., Buse, D.C., Geng, J., Xu, J., Liu, H., and Ma, S. (2023). Efficacy and tolerability of oral gastrodin for medication overuse headache (EASTERN): Study protocol for a multicenter randomized double-blind placebo-controlled trial. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.1095298"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.actbio.2025.06.050","article-title":"Remodeling the blood-air barrier and enhancing the pulmonary microcirculation with a dual-responsive biomimetic nanosystem for precise therapy in acute lung injury","volume":"202","author":"Yan","year":"2025","journal-title":"Acta Biomater."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"90979","DOI":"10.18632\/oncotarget.18773","article-title":"Neuroprotective effect of a novel gastrodin derivative against ischemic brain injury: Involvement of peroxiredoxin and TLR4 signaling inhibition","volume":"8","author":"Mao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"104657","DOI":"10.1016\/j.yrtph.2020.104657","article-title":"Safety evaluation of water extract of Gastrodia elata Blume: Genotoxicity and 28-day oral toxicity studies","volume":"114","author":"Lu","year":"2020","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_77","first-page":"2037","article-title":"Analysis on 315 cases of clinical adverse drug reaction\/event induced by gastrodin","volume":"40","author":"Zheng","year":"2015","journal-title":"Zhongguo Zhong Yao Za Zhi"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8754\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:02:01Z","timestamp":1790766121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":77,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198754"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198754","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]}}}