Gastrodin provides neuroprotection in models of traumatic brain injury via Nrf2 signaling pathway

Main Article Content

Dan Wang
Xiaoqing Dong


apoptosis, gastrodin, Nrf2 pathway, oxidative stress, traumatic brain injury (TBI)


Gastrodin is one of the main active components of Gastrodia elata and has significant therapeutic value for various nervous system diseases. Its medicinal properties include smooth muscle relaxation, anti-necrosis, anti-aging, and anti-apoptosis effects. However, its possible effects on traumatic brain injury (TBI) are still unclear. In this study, the effects of gastroditin on TBI rats were investigated. The results proved that gastrodin had neuroprotective effect on TBI through alleviating brain deficits, decreasing brain water content, inhibiting neuronal apoptosis, and suppressing oxidative stress in brain tissues of TBI rats. Mechanically, gastrodin upregulated the expression of Nrf2 downstream proteins, suggesting the activation of Nrf2 pathway in brain tissues of TBI rats. In conclusion, gastrodin provided neuroprotection in TBI rats via Nrf2 pathway.

Abstract 204 | PDF Downloads 80 HTML Downloads 46 XML Downloads 42


Chen J, Huang Y, Hu X, Bian X, Nian S. Gastrodin prevents homocysteine-induced human umbilical vein endothelial cells injury via PI3K/Akt/eNOS and Nrf2/ARE pathway. J Cell Mol Med. 2021;25(1):345–57. 10.1111/jcmm.16073

de Oliveira MR, Brasil FB, Furstenau CR. Nrf2 mediates the anti-apoptotic and anti-inflammatory effects induced by gastrodin in hydrogen peroxide-treated SH-SY5Y cells. J Mol Neurosci. 2019;69(1):115–22. 10.1007/s12031-019-01339-3

Dong Z, Bian L, Wang YL, Sun LM. Gastrodin protects against high glucose-induced cardiomyocyte toxicity via GSK-3beta-mediated nuclear translocation of Nrf2. Human Exp Toxicol. 2021;40(9):1584–97. 10.1177/09603271211002885

Huibregtse ME, Bazarian JJ, Shultz SR, Kawata K. The biological significance and clinical utility of emerging blood biomarkers for traumatic brain injury. Neurosci Biobehav Rev. 2021;130:433–47. 10.1016/j.neubiorev.2021.08.029

Li S, Bian L, Fu X, Ai Q, Sui Y, Zhang A, et al. Gastrodin pretreatment alleviates rat brain injury caused by cerebral ischemic-reperfusion. Brain Res. 2019;1712:207–16. 10.1016/j.brainres.2019.02.006

Lv H, Liu Y, Zhang B, Zheng Y, Ji H, Li S. The improvement effect of gastrodin on LPS/GalN-induced fulminant hepatitis via inhibiting inflammation and apoptosis and restoring autophagy. Int Immunopharmacol. 2020;85:106627. 10.1016/j.intimp.2020.106627

Merritt VC, Lange RT, Lippa SM, Brickell TA, Soltis AR, Dalgard CL, et al. Apolipoprotein e (APOE) epsilon4 genotype influences memory performance following remote traumatic brain injury in U.S. military service members and veterans. Brain Cogn. 2021;154:105790. 10.1016/j.bandc.2021.105790

Nepal MR, Jeong KS, Kim GH, Cha DH, Kang MJ, Kim JS, et al. Role of intestinal microbiota in metabolism of gastrodin in vitro and in vivo. Metabolites. 2019;9(4):69. 0.3390/metabo9040069

Qin B, Luo N, Li Y, Gong D, Zheng J, Tan X, et al. Protective effect of gastrodin on peripheral neuropathy induced by anti-tumor treatment with vincristine in rat models. Drug Chemical Toxicol. 2021;44(1):84–91. 10.1080/01480545.2018.1547739

Schmitt RR, Kaliyappan K, Muthaiah VPK, Ignatowski TA, Prasad PN, Mahajan SD. Blast-induced injury responsive relative gene expression of traumatic brain injury biomarkers in human brain microvascular endothelial cells. Brain Res. 2021;1770:147642. 10.1016/j.brainres.2021.147642

Sowter N, King L, Calderbank A, Eccles FJR. Factors predicting first appointment attendance at a traumatic brain injury clinical neuropsychology outpatient clinic: a logistic regression analysis. Disabil Rehabil. 2021;Sep 6:1-6. 10.1080/09638288.2021.1970254

Suntai Z, Laha-Walsh K, Albright DL. Effectiveness of remote interventions in improving caregiver stress outcomes for caregivers of people with traumatic brain injury. Rehab Psychol. 2021. 10.1037/rep0000402

Thomas BP, Tarumi T, Wang C, Zhu DC, Tomoto T, Munro Cullum C, et al. Hippocampal and rostral anterior cingulate blood flow is associated with affective symptoms in chronic traumatic brain injury. Brain Res. 2021;1771:147631. 10.1016/j.brainres.2021.147631

Tian ZK, Zhang YJ, Feng ZJ, Jiang H, Cheng C, Sun JM, et al. Nephroprotective effect of gastrodin against lead-induced oxidative stress and inflammation in mice by the GSH, Trx, Nrf2 antioxidant system, and the HMGB1 pathway. Toxicol Res. 2021;10(2):249–63. 10.1093/toxres/tfab003

Wearne TA, Logan JA, Trimmer EM, Wilson E, Filipcikova M, Kornfeld E, et al. Regulating emotion following severe traumatic brain injury: a randomized controlled trial of heart-rate variability biofeedback training. Brain Inj. 2021;Sep 6:1–12. 10.1080/02699052.2021.1972337

Xiao H, Jiang Q, Qiu H, Wu K, Ma X, Yang J, et al. Gastrodin promotes hippocampal neurogenesis via PDE9-cGMP-PKG pathway in mice following cerebral ischemia. Neurochem Int. 2021;150:105171. 10.1016/j.neuint.2021.105171

Yang GM, Li L, Xue FL, Ma CL, Zeng XF, Zhao YN, et al. The potential role of PKA/CREB signaling pathway concerned with gastrodin administration on methamphetamine-induced conditioned place preference rats and SH-SY5Y cell line. Neurotoxicity research. 2020;37(4):926–35. 10.1007/s12640-019-00150-7

Yao YY, Bian LG, Yang P, Sui Y, Li R, Chen YL, et al. Gastrodin attenuates proliferation and inflammatory responses in activated microglia through Wnt/beta-catenin signaling pathway. Brain Res. 2019;1717:190–203. 10.1016/j.brainres.2019.04.025

Yao YY, Li R, Guo YJ, Zhao Y, Guo JZ, Ai QL, et al. Gastrodin attenuates lipopolysaccharide-induced inflammatory response and migration via the Notch-1 signaling pathway in activated microglia. Neuromolecular Med. 2021. 10.1007/s12017-021-08671-1 [online ahead of print].

Yuan F, Xu X, Wu Y, Duan S, Wu H. Gastrodin ameliorates acute rejection via IRE1alpha/TRAF2/NF-kappaB in rats receiving liver allografts. BioMed Res Int. 2019;2019:9276831. 10.1155/2019/9276831

Zhang HB, Yuan B, Huang HF, Qu SM, Yang SK. Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation Braz J Med Biol Res (2018) 51(10): e7439. 10.1590/1414-431X20187439

Zhang HS, Liu MF, Ji XY, Jiang CR, Li ZL, OuYang B. Gastrodin combined with rhynchophylline inhibits cerebral ischaemia-induced inflammasome activation via upregulating miR-21-5p and miR-331-5p. Life Sci. 2019;239:116935. 10.1016/j.lfs.2019.116935