Research Paper Volume 14, Issue 6 pp 2607—2627

2, 3, 5, 4’-tetrahydroxystilbene-2-O-beta-D-glucoside protects against neuronal cell death and traumatic brain injury-induced pathophysiology

Yu-Hsin Chen1,2, , Yen-Chou Chen1, , Yu-Tang Chin3, , Ching-Chiung Wang4, , Ling-Ling Hwang1,2, , Liang-Yo Yang5,6, , Dah-Yuu Lu7,8, ,

  • 1 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
  • 2 Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
  • 3 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan
  • 4 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
  • 5 Department of Physiology, School of Medicine, College of Medicine, China Medical University, Taichung 404333, Taiwan
  • 6 Laboratory of Neural Repair, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan
  • 7 Department of Pharmacology, School of Medicine, College of Medicine, China Medical University, Taichung 404333, Taiwan
  • 8 Department of Photonics and Communication Engineering, Asia University, Taichung 41354, Taiwan

Received: October 28, 2021       Accepted: March 1, 2022       Published: March 21, 2022
How to Cite

Copyright: © 2022 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Traumatic brain injury (TBI) is a global health issue that affects at least 10 million people per year. Neuronal cell death and brain injury after TBI, including apoptosis, inflammation, and excitotoxicity, have led to detrimental effects in TBI. 2, 3, 5, 4’-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), a water-soluble compound extracted from the Chinese herb Polygonum multiflorum, has been shown to exert various biological functions. However, the effects of THSG on TBI is still poorly understood. THSG reduced L-glutamate-induced DNA fragmentation and protected glial and neuronal cell death after L-glutamate stimulation. Our results also showed that TBI caused significant behavioral deficits in the performance of beam walking, mNSS, and Morris water maze tasks in a mouse model. Importantly, daily administration of THSG (60 mg/kg/day) after TBI for 21 days attenuated the injury severity score, promoted motor coordination, and improved cognitive performance post-TBI. Moreover, administration of THSG also dramatically decreased the brain lesion volume. THSG reduced TBI-induced neuronal apoptosis in the brain cortex 24 h after TBI. Furthermore, THSG increased the number of immature neurons in the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus. Our results demonstrate that THSG exerts neuroprotective effects on glutamate-induced excitotoxicity and glial and neuronal cell death. The present study also demonstrated that THSG effectively protects against TBI-associated motor and cognitive impairment, at least in part, by inhibiting TBI-induced apoptosis and promoting neurogenesis.


AMPA: α-amino-3-hydroxy-5-methyl-isoxazole propionate; BDNF: brain-derived neurotrophic factor; CCI: control cortical impact; CNS: central nervous system; CSF: cerebrospinal fluid; DAPI: 4',6-diamidino-2-phenylindole; DCX: Doublecortin; DG: dentate gyrus; DIV: Days in vitro; DNA: deoxyribonucleic acid; FBS: fetal bovine serum; HG-DMEM: high glucose-Dulbecco's modified Eagle medium; LDH: lactate dehydrogenase; MAP-2: microtubule associated protein 2; mNSS: modified neurological severity score; MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NeuN: neuronal nuclear protein; NMDA: N-methyl-D-aspartate; OCT compound: optimal cutting temperature compound; PM: polygonum multiflorum; SGZ: subgranular zone; TBI: traumatic brain injury; THSG: 2, 3, 5, 4’-tetrahydroxystilbene-2-O-beta-D-glucoside; TrkB: tropomyosin receptor kinase B; TUNEL: terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling.