Vitisin A, a Resveratrol Tetramer, Improves Scopolamine-Induced Impaired Learning and Memory Functions in Amnesiac ICR Mice

  • Biomedicines. 2022 Jan 26;10(2):273. doi: 10.3390/biomedicines10020273.
Lih-Geeng Chen  1  2 ,  Ching-Chiung Wang  2  3  4 ,  Yi-Shan Lee  3 ,  Yi-Yan Sie  5 ,  Chi-I Chang  6 ,  Wen-Chi Hou  3  5
Affiliations
  • 1. Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan.
  • 2. Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan.
  • 3. Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, Taiwan.
  • 4. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
  • 5. Ph.D. Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
  • 6. Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 912, Taiwan.
PMID: 35203483 DOI: 10.3390/biomedicines10020273
Abstract

Resveratrol has been reported to exhibit neuroprotective activities in vitro and in vivo. However, little is known about resveratrol tetramers of hopeaphenol, vitisin A, and vitisin B with the same molecular mass in the improvement of degenerative disorders. In this study, two 95% ethanol extracts (95EE) from stem parts of Vitis thunbergii Sieb. & Zucc. (VT-95EE) and from the root (R) parts of Vitis thunbergii var. taiwaniana (VTT-R-95EE) showed comparable acetylcholinesterase (AChE) inhibitory activities. It was found that VT-95EE and VTT-R-95EE showed different distribution patterns of identified resveratrol and resveratrol tetramers of hopeaphenol, vitisin A, and vitisin B based on the analyses of HPLC chromatographic profiles. The hopeaphenol, vitisin A, and vitisin B, showed AChE and monoamine oxidase-B inhibitions in a dose-dependent manner, among which vitisin B and vitisin A exhibited much better activities than those of resveratrol, and had neuroprotective activities against methylglyoxal-induced SH-SY5Y cell deaths. The scopolamine-induced amnesiac ICR mice treated with VT-95EE and its ethyl acetate-partitioned fraction (VT-95EE-EA) at doses of 200 and 400 mg/kg, or vitisin A at a dose of 40 mg/kg, but not vitisin B (40 mg/kg), were shown significantly to improve the impaired learning behaviors by passive avoidance tests compared to those in the control without drug treatments (p < 0.05). Compared to mice in the control group, the brain extracts in the vitisin A-treated mice or donepezil-treated mice showed significant reductions in AChE activities and malondialdehyde levels (p < 0.05), and elevated the reduced protein expressions of brain-derived neurotrophic factor (BDNF) and BDNF receptor, tropomyosin receptor kinase B (TrkB). These results revealed that vitisin A was the active constituent in the VT-95EE and VTT-95EE, and the VT medicinal plant and that the endemic variety of VTT has potential in developing functional foods for an unmet medical need for neurodegenerative disorders.

Keywords
acetylcholinesterase; brain-derived neurotrophic factor (BDNF); scopolamine; vitisin A.
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