Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
권호 표지
DOI QR코드

DOI QR Code

Preclinical Evidence and Underlying Mechanisms of Polygonum multiflorum and Its Chemical Constituents Against Cognitive Impairments and Alzheimer's Disease

  • Jihyun Cha (Department of Korean Medicine, School of Korean Medicine, Pusan National University) ;
  • Ji Hwan Yun (Department of Korean Medicine, School of Korean Medicine, Pusan National University) ;
  • Ji Hye Choi (Department of Korean Medicine, School of Korean Medicine, Pusan National University) ;
  • Jae Ho Lee (Department of Korean Medical Science, School of Korean Medicine, Pusan National University) ;
  • Byung Tae Choi (Department of Korean Medicine, School of Korean Medicine, Pusan National University) ;
  • Hwa Kyoung Shin (Department of Korean Medicine, School of Korean Medicine, Pusan National University)
  • Received : 2024.02.15
  • Accepted : 2024.03.05
  • Published : 2024.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: Cognitive impairments, ranging from mild to severe, adversely affect daily functioning, quality of life, and work capacity. Despite significant efforts in the past decade, more than 200 promising drug candidates have failed in clinical trials. Herbal remedies are gaining interest as potential treatments for dementia due to their long history and safety, making them valuable for drug development. This review aimed to examine the mechanisms behind the effect of Polygonum multiflorum on cognitive function. Methods: This study focused primarily on the effects of Polygonum multiflorum and its chemical constituents on cognitive behavioral outcomes including the Morris water maze, the passive avoidance test, and the Y maze, as well as pathogenic targets of cognitive impairment and Alzheimer's disease (AD) like amyloid deposition, amyloid precursor protein, tau hyperphosphorylation, and cognitive decline. Additionally, a thorough evaluation of the mechanisms behind Polygonum multiflorum's impact on cognitive function was conducted. We reviewed the most recent data from preclinical research done on experimental models, particularly looking at Polygonum multiflorum's effects on cognitive decline and AD. Results: According to recent research, Poligonum multiflorum and its bioactive components, stilbene, and emodin, influence cognitive behavioral results and regulate the pathological target of cognitive impairment and AD. Their mechanisms of action include reducing oxidative and mitochondrial damage, regulating neuroinflammation, halting apoptosis, and promoting increased neurogenesis and synaptogenesis. Conclusion: This review serves as a comprehensive compilation of current experiments on AD and other cognitive impairment models related to the therapeutic effects of Polygonum multiflorum. We believe that these findings can serve as a basis for future clinical trials and have potential applications in the treatment of human neurological disorders.

Keywords

Acknowledgement

This work was supported by a 2-Year Research Grant of Pusan National University.

References

  1. Poulos CJ, Bayer A, Beaupre L, Clare L, Poulos RG, Wang RH, et al. A comprehensive approach to reablement in dementia. Alzheimers Dement (N Y). 2017;3(3):450-8.  https://doi.org/10.1016/j.trci.2017.06.005
  2. Hugo J, Ganguli M. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment. Clin Geriatr Med. 2014;30(3):421-42.  https://doi.org/10.1016/j.cger.2014.04.001
  3. Gonzales MM, Garbarino VR, Pollet E, Palavicini JP, Kellogg DL Jr, Kraig E, et al. Biological aging processes underlying cognitive decline and neurodegenerative disease. J Clin Invest. 2022;132(10):e158453. 
  4. Sery O, Povova J, Misek I, Pesak L, Janout V. Molecular mechanisms of neuropathological changes in Alzheimer's disease: a review. Folia Neuropathol. 2013;51(1):1-9.  https://doi.org/10.5114/fn.2013.34190
  5. Bondi MW, Edmonds EC, Salmon DP. Alzheimer's disease: past, present, and future. J Int Neuropsychol Soc. 2017;23(9-10):818-31.  https://doi.org/10.1017/S135561771700100X
  6. Rao RV, Descamps O, John V, Bredesen DE. Ayurvedic medicinal plants for Alzheimer's disease: a review. Alzheimers Res Ther. 2012;4(3):22. 
  7. Gregory J, Vengalasetti YV, Bredesen DE, Rao RV. Neuroprotective herbs for the management of Alzheimer's disease. Biomolecules. 2021;11(4):543. 
  8. Lin L, Ni B, Lin H, Zhang M, Li X, Yin X, et al. Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: a review. J Ethnopharmacol. 2015;159:158-83.  https://doi.org/10.1016/j.jep.2014.11.009
  9. Chan YC, Cheng FC, Wang MF. Beneficial effects of different Polygonum multiflorum Thunb. extracts on memory and hippocampus morphology. J Nutr Sci Vitaminol (Tokyo). 2002;48(6):491-7.  https://doi.org/10.3177/jnsv.48.491
  10. Chan YC, Wang MF, Chang HC. Polygonum multiflorum extracts improve cognitive performance in senescence accelerated mice. Am J Chin Med. 2003;31(2):171-9.  https://doi.org/10.1142/S0192415X03000862
  11. Zhou L, Hou Y, Yang Q, Du X, Li M, Yuan M, et al. Tetrahydroxystilbene glucoside improves the learning and memory of amyloid-β(1-42)-injected rats and may be connected to synaptic changes in the hippocampus. Can J Physiol Pharmacol. 2012;90(11):1446-55.  https://doi.org/10.1139/y2012-121
  12. Xie M, Zhang G, Yin W, Hei XX, Liu T. Cognitive enhancing and antioxidant effects of tetrahydroxystilbene glucoside in Aβ1-42-induced neurodegeneration in mice. J Integr Neurosci. 2018;17(3-4):355-65.  https://doi.org/10.3233/JIN-170059
  13. Luo H, Li Y, Guo J, Liu Z, Zhang Z, Wang Y, et al. Tetrahydroxy stilbene glucoside improved the behavioral disorders of APP695V717I transgenic mice by inhibiting the expression of Beclin-1 and LC3-II. J Tradit Chin Med. 2015;35(3):295-300.  https://doi.org/10.1016/S0254-6272(15)30100-X
  14. Zhang L, Xing Y, Ye CF, Ai HX, Wei HF, Li L. Learning-memory deficit with aging in APP transgenic mice of Alzheimer's disease and intervention by using tetrahydroxystilbene glucoside. Behav Brain Res. 2006;173(2):246-54.  https://doi.org/10.1016/j.bbr.2006.06.034
  15. Wang R, Tang Y, Feng B, Ye C, Fang L, Zhang L, et al. Changes in hippocampal synapses and learning-memory abilities in age-increasing rats and effects of tetrahydroxystilbene glucoside in aged rats. Neuroscience. 2007;149(4):739-46.  https://doi.org/10.1016/j.neuroscience.2007.07.065
  16. Shen C, Sun FL, Zhang RY, Zhang L, Li YL, Zhang L, et al. Tetrahydroxystilbene glucoside ameliorates memory and movement functions, protects synapses and inhibits α-synuclein aggregation in hippocampus and striatum in aged mice. Restor Neurol Neurosci. 2015;33(4):531-41.  https://doi.org/10.3233/RNN-150514
  17. Chen YH, Chen YC, Chin YT, Wang CC, Hwang LL, Yang LY, et al. 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside protects against neuronal cell death and traumatic brain injury-induced pathophysiology. Aging (Albany NY). 2022;14(6):2607-27.  https://doi.org/10.18632/aging.203958
  18. Chen T, Yang YJ, Li YK, Liu J, Wu PF, Wang F, et al. Chronic administration tetrahydroxystilbene glucoside promotes hippocampal memory and synaptic plasticity and activates ERKs, CaMKII and SIRT1/miR-134 in vivo. J Ethnopharmacol. 2016;190:74-82.  https://doi.org/10.1016/j.jep.2016.06.012
  19. Zeng P, Shi Y, Wang XM, Lin L, Du YJ, Tang N, et al. Emodin rescued hyperhomocysteinemia-induced dementia and Alzheimer's disease-like features in rats. Int J Neuropsychopharmacol. 2019;22(1):57-70.  https://doi.org/10.1093/ijnp/pyy090
  20. Um MY, Choi WH, Aan JY, Kim SR, Ha TY. Protective effect of Polygonum multiflorum Thunb on amyloid beta-peptide 25- 35 induced cognitive deficits in mice. J Ethnopharmacol. 2006;104(1-2):144-8.  https://doi.org/10.1016/j.jep.2005.08.054
  21. Park HR, Kim JY, Lee Y, Chun HJ, Choi YW, Shin HK, et al. PMC-12, a traditional herbal medicine, enhances learning memory and hippocampal neurogenesis in mice. Neurosci Lett. 2016;617:254-63.  https://doi.org/10.1016/j.neulet.2016.02.036
  22. Ahn SM, Kim YR, Kim HN, Choi YW, Lee JW, Kim CM, et al. Neuroprotection and spatial memory enhancement of four herbal mixture extract in HT22 hippocampal cells and a mouse model of focal cerebral ischemia. BMC Complement Altern Med. 2015;15:202. 
  23. Park MY, Jung YS, Park JH, Choi YW, Lee J, Kim CM, et al. PMC-12, a prescription of traditional Korean medicine, improves amyloid β-induced cognitive deficits through modulation of neuroinflammation. Evid Based Complement Alternat Med. 2015;2015:768049. 
  24. Yin X, Chen C, Xu T, Li L, Zhang L. Tetrahydroxystilbene glucoside modulates amyloid precursor protein processing via activation of AKT-GSK3β pathway in cells and in APP/PS1 transgenic mice. Biochem Biophys Res Commun. 2018;495(1):672-8.  https://doi.org/10.1016/j.bbrc.2017.11.059
  25. Zhang RY, Zhang L, Zhang L, Wang YL, Li L. Anti-amyloidgenic and neurotrophic effects of tetrahydroxystilbene glucoside on a chronic mitochondrial dysfunction rat model induced by sodium azide. J Nat Med. 2018;72(3):596-606.  https://doi.org/10.1007/s11418-018-1177-y
  26. Luo HB, Yang JS, Shi XQ, Fu XF, Yang QD. Tetrahydroxy stilbene glucoside reduces the cognitive impairment and overexpression of amyloid precursor protein induced by aluminum exposure. Neurosci Bull. 2009;25(6):391-6.  https://doi.org/10.1007/s12264-009-0601-4
  27. Gao Y, Li J, Wu Q, Wang S, Yang S, Li X, et al. Tetrahydroxy stilbene glycoside ameliorates Alzheimer's disease in APP/PS1 mice via glutathione peroxidase related ferroptosis. Int Immunopharmacol. 2021;99:108002. 
  28. Zhang L, Yu S, Zhang R, Xing Y, Li Y, Li L. Tetrahydroxystilbene glucoside antagonizes age-related α-synuclein overexpression in the hippocampus of APP transgenic mouse model of Alzheimer's disease. Restor Neurol Neurosci. 2013;31(1):41-52.  https://doi.org/10.3233/RNN-120260
  29. He H, Wang S, Tian J, Chen L, Zhang W, Zhao J, et al. Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside in the MPTP-induced mouse model of Parkinson's disease: involvement of reactive oxygen species-mediated JNK, P38 and mitochondrial pathways. Eur J Pharmacol. 2015;767:175-82.  https://doi.org/10.1016/j.ejphar.2015.10.023
  30. Li X, Li Y, Chen J, Sun J, Li X, Sun X, et al. Tetrahydroxystilbene glucoside attenuates MPP+-induced apoptosis in PC12 cells by inhibiting ROS generation and modulating JNK activation. Neurosci Lett. 2010;483(1):1-5.  https://doi.org/10.1016/j.neulet.2010.07.027
  31. Tao L, Li X, Zhang L, Tian J, Li X, Sun X, et al. Protective effect of tetrahydroxystilbene glucoside on 6-OHDA-induced apoptosis in PC12 cells through the ROS-NO pathway. PLoS One. 2011;6(10):e26055. 
  32. Wang T, Gu J, Wu PF, Wang F, Xiong Z, Yang YJ, et al. Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-kappaB pathways and inhibition of intracellular ROS/RNS generation. Free Radic Biol Med. 2009;47(3):229-40.  https://doi.org/10.1016/j.freeradbiomed.2009.02.027
  33. Kim HN, Kim YR, Jang JY, Choi YW, Baek JU, Hong JW, et al. Neuroprotective effects of Polygonum multiflorum extract against glutamate-induced oxidative toxicity in HT22 hippocampal cells. J Ethnopharmacol. 2013;150(1):108-15.  https://doi.org/10.1016/j.jep.2013.08.014
  34. Gao Y, Li J, Li J, Hu C, Zhang L, Yan J, et al. Tetrahydroxy stilbene glycoside alleviated inflammatory damage by mitophagy via AMPK related PINK1/Parkin signaling pathway. Biochem Pharmacol. 2020;177:113997. 
  35. Jiao C, Gao F, Ou L, Yu J, Li M, Wei P, et al. Tetrahydroxystilbene glycoside antagonizes β-amyloid-induced inflammatory injury in microglia cells by regulating PU.1 expression. Neuroreport. 2018;29(10):787-93.  https://doi.org/10.1097/WNR.0000000000001032
  36. Zhang F, Wang YY, Yang J, Lu YF, Liu J, Shi JS. Tetrahydroxystilbene glucoside attenuates neuroinflammation through the inhibition of microglia activation. Oxid Med Cell Longev. 2013;2013:680545. 
  37. Park SY, Jin ML, Ko MJ, Park G, Choi YW. Anti-neuroinflammatory effect of emodin in LPS-stimulated microglia: involvement of AMPK/Nrf2 activation. Neurochem Res. 2016;41(11):2981-92.  https://doi.org/10.1007/s11064-016-2018-6
  38. Park SY, Jin ML, Kang NJ, Park G, Choi YW. Anti-inflammatory effects of novel polygonum multiflorum compound via inhibiting NF-κB/MAPK and upregulating the Nrf2 pathways in LPS-stimulated microglia. Neurosci Lett. 2017;651:43-51.  https://doi.org/10.1016/j.neulet.2017.04.057
  39. Park SY, Jin ML, Chae SY, Ko MJ, Choi YH, Park G, et al. Novel compound from Polygonum multiflorum inhibits inflammatory response in LPS-stimulated microglia by upregulating AMPK/Nrf2 pathways. Neurochem Int. 2016;100:21-9.  https://doi.org/10.1016/j.neuint.2016.08.006
  40. Lee SY, Ahn SM, Wang Z, Choi YW, Shin HK, Choi BT. Neuroprotective effects of 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside from Polygonum multiflorum against glutamate-induced oxidative toxicity in HT22 cells. J Ethnopharmacol. 2017;195:64-70.  https://doi.org/10.1016/j.jep.2016.12.001
  41. Sun FL, Zhang L, Zhang RY, Li L. Tetrahydroxystilbene glucoside protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity. Eur J Pharmacol. 2011;660(2-3):283-90.  https://doi.org/10.1016/j.ejphar.2011.03.046
  42. Qin R, Li X, Li G, Tao L, Li Y, Sun J, et al. Protection by tetrahydroxystilbene glucoside against neurotoxicity induced by MPP+: the involvement of PI3K/Akt pathway activation. Toxicol Lett. 2011;202(1):1-7.  https://doi.org/10.1016/j.toxlet.2011.01.001
  43. Ahn SM, Kim YR, Kim HN, Shin HK, Choi BT. Beneficial effects of Polygonum multiflorum on hippocampal neuronal cells and mouse focal cerebral ischemia. Am J Chin Med. 2015;43(4):637-51.  https://doi.org/10.1142/S0192415X15500391
  44. Ren TT, Fan SR, Lang XY, Yu Y, Lan R, Qin XY. 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside eliminates staurosporine-induced cytotoxicity by restoring BDNF-TrkB/Akt signaling axis. Int J Med Sci. 2020;17(14):2207-13.  https://doi.org/10.7150/ijms.47919
  45. Wang T, Yang YJ, Wu PF, Wang W, Hu ZL, Long LH, et al. Tetrahydroxystilbene glucoside, a plant-derived cognitive enhancer, promotes hippocampal synaptic plasticity. Eur J Pharmacol. 2011;650(1):206-14. https://doi.org/10.1016/j.ejphar.2010.10.002