Planta Med 2020; 86(18): 1389-1399
DOI: 10.1055/a-1212-3212
Biological and Pharmacological Activity
Original Papers

Extract of the Aerial Part of Polygala tenuifolia Attenuates d-Galactose/NaNO2-induced Learning and Memory Impairment in Mice

Dian Zhang
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xiʼan, China
,
Xiao Wang
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xiʼan, China
,
Rong Li
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xiʼan, China
,
Lin Wang
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xiʼan, China
,
Zihao Zhou
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xiʼan, China
,
Qi Fu
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xiʼan, China
,
Yanjun Cao
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xiʼan, China
,
Minfeng Fang
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xiʼan, China
› Author Affiliations
Supported by: the Shaanxi Provincial Education Department Serves Local Special Projects 2018JC032
Supported by: the open funding of Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University ZSK2018006
Supported by: the Key Research and Development Plan in Shaanxi province 2018ZDXM-SF-014
Supported by: the Public health specialty in the Department of Traditional Chinese Medicine 2018-43

Abstract

Alzheimerʼs disease, one of the most common types of age-related dementia, is characterized by memory deterioration and behavior disorder. The aboveground part of Polygala tenuifolia is a traditional Chinese medicine used for the treatment of amnesia. This study was conducted to investigate the ameliorating effect of the aerial part of P. tenuifolia on d-galactose/NaNO2-induced learning and memory impairment in mice. d-galactose (120 mg/kg) and NaNO2 (90 mg/kg) were injected intraperitoneally for 60 days to induce learning and memory impairment in mice. The aerial part of P. tenuifolia (25, 50, and 100 mg/kg) and piracetam (200 mg/kg) were simultaneously administered orally on days 15 – 60. Results of this study showed that aerial part of P. tenuifolia significantly decreased the latency time and increased the number of platform crossings in the Morris water maze compared with the Model group. Moreover, the aerial part of P. tenuifolia significantly increased the latency time and decreased the error frequency in the step-down and step-through tests compared with the Model group. Meanwhile, the aerial part of P. tenuifolia was able to regulate the cholinergic system by increasing the levels of ACh and ChAT and decreasing the level of AChe. The aerial part of P. tenuifolia also significantly attenuated the levels of interleukin-1 beta and malonaldehyde and enhanced the interleukin-10 and glutathione levels and superoxide dismutase activity. Furthermore, treatment with aerial part of P. tenuifolia increased the protein and mRNA expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the hippocampus. These results suggest that the aerial part of P. tenuifolia can ameliorate learning and memory impairments by modulating cholinergic activity, inhibiting neuroinflammation and oxidative stress, and regulating the brain-derived neurotrophic factor and tropomyosin receptor kinase B signaling pathway.



Publication History

Received: 16 December 2019

Accepted after revision: 02 July 2020

Article published online:
14 August 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Prince M, Wimo A, Guerchet M, Ali GC, Wu Y, Prina AM. World Alzheimer Report 2015: The global impact of dementia. an analysis of prevalence, incidence, costs and trends. London: Alzheimerʼs Disease International; 2015
  • 2 Alzheimerʼs Association. 2019 Alzheimerʼs disease facts and figures. Alzheimerʼs & Dement 2019; 15: 321-387
  • 3 Bekinschtein P, Cammarota M, Medina JH. BDNF and memory processing. Neuropharmacology 2014; 76 Pt C: 677-683
  • 4 Fruhauf-Perez PK, Temp FR, Pillat MM, Signor C, Wendel AL, Ulrich H, Mello CF, Rubin MA. Spermine protects from LPS-induced memory deficit via BDNF and TrkB activation. Neurobiol Learn Mem 2018; 149: 135-143
  • 5 Tait L, Stothart G, Coulthard E, Brown JT, Kazanina N, Goodfellow M. Network substrates of cognitive impairment in Alzheimerʼs Disease. Clin Neurophysiol 2019; 130: 1581-1595
  • 6 Tanila H. The role of BDNF in Alzheimerʼs disease. Neurobiol Dis 2017; 97: 114-118
  • 7 Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 2010; 345: 91-104
  • 8 Schrag M, Mueller C, Zabel M, Crofton A, Kirsch WM, Ghribi O, Squitti R, Perry G. Oxidative stress in blood in Alzheimerʼs disease and mild cognitive impairment: a meta-analysis. Neurobiol Dis 2013; 59: 100-110
  • 9 Flannery PJ, Trushina E. Mitochondrial dynamics and transport in Alzheimerʼs disease. Mol Cell Neurosci 2019; 98: 109-120
  • 10 Morgan AR, Touchard S, Leckey C, OʼHagan C, Nevado-Holgado AJ. NIMA Consortium, Barkhof F, Bertram L, Blin O, Bos I, Dobricic V, Engelborghs S, Frisoni G, Frölich L, Gabel S, Johannsen P, Kettunen P, Kłoszewska I, Legido-Quigley C, Lleó A, Martinez-Lage P, Mecocci P, Meersmans K, Molinuevo JL, Peyratout G, Popp J, Richardson J, Sala I, Scheltens P, Streffer J, Soininen H, Tainta-Cuezva M, Teunissen C, Tsolaki M, Vandenberghe R, Visser PJ, Vos S, Wahlund LO, Wallin A, Westwood S, Zetterberg H, Lovestone S, Morgan BP, Annex: NIMA – Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimerʼs Disease. Inflammatory biomarkers in Alzheimerʼs disease plasma. Alzheimers Dement 2019; 15: 776-787
  • 11 Ozben T, Ozben S. Neuro-inflammation and anti-inflammatory treatment options for Alzheimerʼs disease. Clin Biochem 2019; 72: 87-89
  • 12 Pena-Bautista C, Baquero M, Vento M, Chafer-Pericas C. Free radicals in Alzheimerʼs disease: lipid peroxidation biomarkers. Clinica Chimica Acta 2019; 491: 85-90
  • 13 Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimerʼs disease. Alzheimers Dement 2018; 4: 575-590
  • 14 Omar SH, Scott CJ, Hamlin AS, Obied HK. The protective role of plant biophenols in mechanisms of Alzheimerʼs disease. J Nutr Biochem 2017; 47: 1-20
  • 15 Lin Z, Gu J, Xiu J, Mi T, Dong J, Tiwari JK. Traditional chinese medicine for senile dementia. Evid Based Complement Alternat Med 2012; 2012: 692621
  • 16 Dey A, Bhattacharya R, Mukherjee A, Pandey DK. Natural products against Alzheimerʼs disease: Pharmaco-therapeutics and biotechnological interventions. Biotechnol Adv 2017; 35: 178-216
  • 17 Shi T, Li Y, Jiang Y. Isolation of flavonoids from the aerial parts of Polygala tenuifolia Willd. and their antioxidant activities. Chinese Pharmaceut J 2013; 022: 36-39
  • 18 Yang XJ, Zou PP, Tu PF, Jiang Y. HPLC determination of mangiferin in the leaves of Aquilaria sinensis and the different aerial parts of Polygala tenuifolia . Chinese J Pharmaceut Anal 2012; 32: 1175-1178
  • 19 Liu L, Lu Y, Kong H, Li L, Marshall C, Xiao M, Ding J, Gao J, Hu G. Aquaporin–4 deficiency exacerbates brain oxidative damage and memory deficits induced by long-term ovarian hormone deprivation and D-galactose injection. Int J Neuropsychopharmacol 2012; 15: 14
  • 20 Krivinko JM, Koppel J, Savonenko A, Sweet RA. Animal models of psychosis in Alzheimer Disease. Am J Geriatr Psychiatr 2019; 28: 1-19 doi:10.1016/j.jagp.2019.05.009
  • 21 McKeever PM, Kim T, Hesketh AR, MacNair L, Miletic D, Favrin G, Oliver SG, Zhang Z, St George-Hyslop P, Robertson J. Cholinergic neuron gene expression differences captured by translational profiling in a mouse model of Alzheimerʼs disease. Neurobiol Aging 2017; 57: 104-119
  • 22 Klaassens BL, van Gerven JMA, Klaassen ES, van der Grond J, Rombouts S. Cholinergic and serotonergic modulation of resting state functional brain connectivity in Alzheimerʼs disease. Neuroimage 2019; 199: 143-152
  • 23 Teipel S, Heinsen H, Amaro EJ, Grinberg LT, Krause B, Grothe M. Cholinergic basal forebrain atrophy predicts amyloid burden in Alzheimerʼs disease. Neurobiol Aging 2014; 35: 482-491
  • 24 Bastin C, Delhaye E, Moulin C, Barbeau EJ. Novelty processing and memory impairment in Alzheimerʼs disease: a review. Neurosci Biobehav Rev 2019; 100: 237-249
  • 25 Tapia-Arancibia L, Aliaga E, Silhol M, Arancibia S. New insights into brain BDNF function in normal aging and Alzheimer disease. Brain Res Rev 2008; 59: 201-220
  • 26 Jiang T, Sun Q, Chen S. Oxidative stress: A major pathogenesis and potential therapeutic target of antioxidative agents in Parkinsonʼs disease and Alzheimerʼs disease. Prog Neurobiol 2016; 147: 1-19
  • 27 Feng ST, Wang ZZ, Yuan YH, Sun HM, Chen NH, Zhang Y. Mangiferin: A multipotent natural product preventing neurodegeneration in Alzheimerʼs and Parkinsonʼs disease models. Pharmacol Res 2019; 146: 104336
  • 28 Mamelak M. Alzheimerʼs disease, oxidative stress and gammahydroxybutyrate. Neurobiol Aging 2007; 28: 1340-1360
  • 29 Zverova M. Clinical aspects of Alzheimerʼs disease. Clin Biochem 2019; 72: 3-6
  • 30 Fish PV, Steadman D, Bayle ED, Whiting P. New approaches for the treatment of Alzheimerʼs disease. Bioorg Med Chem Lett 2019; 29: 125-133
  • 31 Zheng XX, Chen YW, Yue YS, Li YC, Xia SZ, Li Y, Deng HH, He J, Cao YJ. Icariin ameliorates learning and memory impairments through ERK/CaMKIIalpha/CREB signaling and HPA axis in prenatally stressed female offspring. Biomed Pharmacother 2019; 117: 109077