Chen Lih-Geeng, Wang Ching-Chiung, Lee Yi-Shan, Sie Yi-Yan, Chang Chi-I, Hou Wen-Chi
Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan.
Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan.
Biomedicines. 2022 Jan 26;10(2):273. doi: 10.3390/biomedicines10020273.
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 Sieb. & Zucc. (VT-95EE) and from the root (R) parts of var. (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 ( < 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 ( < 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.
白藜芦醇已被报道在体外和体内均具有神经保护活性。然而，对于具有相同分子量的蛇葡萄素、葡萄素A和葡萄素B的白藜芦醇四聚体在改善退行性疾病方面的了解却很少。在本研究中，来自Sieb. & Zucc.茎部的两种95%乙醇提取物（95EE）（VT - 95EE）和来自变种根（R）部的提取物（VTT - R - 95EE）表现出相当的乙酰胆碱酯酶（AChE）抑制活性。基于高效液相色谱（HPLC）色谱图分析发现，VT - 95EE和VTT - R - 95EE中鉴定出的白藜芦醇以及蛇葡萄素、葡萄素A和葡萄素B的白藜芦醇四聚体呈现出不同的分布模式。蛇葡萄素、葡萄素A和葡萄素B对AChE和单胺氧化酶 - B的抑制呈剂量依赖性，其中葡萄素B和葡萄素A表现出比白藜芦醇更好的活性，并且对甲基乙二醛诱导的SH - SY5Y细胞死亡具有神经保护活性。用VT - 95EE及其乙酸乙酯分配部分（VT - 95EE - EA）以200和400 mg/kg的剂量处理，或用40 mg/kg剂量的葡萄素A处理，但不用40 mg/kg剂量的葡萄素B处理的东莨菪碱诱导的失忆ICR小鼠，与未进行药物治疗的对照组相比，通过被动回避试验显示出显著改善受损的学习行为（P < 0.05）。与对照组小鼠相比，葡萄素A处理组小鼠或多奈哌齐处理组小鼠的脑提取物中AChE活性和丙二醛水平显著降低（P < 0.05），并且脑源性神经营养因子（BDNF）和BDNF受体原肌球蛋白受体激酶B（TrkB）的蛋白表达降低情况得到改善。这些结果表明，葡萄素A是VT - 95EE和VTT - 95EE以及VT药用植物中的活性成分，并且VTT的地方变种在开发针对神经退行性疾病未满足医疗需求的功能性食品方面具有潜力。
