Advanced Search

Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 2: 289 - 302

DOI: https://doi.org/10.19852/j.cnki.jtcm.20240203.007

Efficacy of Sailuotong (塞络通) on neurovascular unit in amyloid precursor protein/presenilin-1 transgenic mice with Alzheimer’s disease

  • Linjuan SUN ,
  • Chengfu LI ,
  • Jiangang LIU ,
  • Nannan LI ,
  • Fuhua HAN ,
  • Dandan QIAO ,
  • Zhuang TAO ,
  • Min ZHAN ,
  • Wenjie CHEN ,
  • Xiaohui ZHANG ,
  • Chenguang TONG ,
  • Dong CHEN ,
  • Jiangxia Qi ,
  • Yang LIU ,
  • Xiao LIANG ,
  • Xiaoying ZHENG ,
  • Yunling ZHANG
Expand
  • 1 Department of Neurology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
    2 China Population and Development Research Center, Beijing 100081, China
    3 Department of Institute of Population Research, Peking University, Beijing 100087, China
    4 Graduate School of China Academy of Chinese Medical Sciences, Beijing 100700, China
    5 Graduate School of Beijing University of Chinese Medicine, Beijing 100029, China

Received date: 2022-12-22

  Accepted date: 2023-04-08

  Online published: 2024-03-05

Supported by

National Natural Science Foundation of China: Experimental study on the treatment of transgenic mice with Alzheimer's disease by protecting neurovascular unit by supplementing Qi and activating blood circulation investigate(81503450)

Fold

Abstract

OBJECTIVE: To discuss the influence of Sailuotong (塞络通, SLT) on the Neurovascular Unit (NVUs) of amyloid precursor protein (APP)/presenilin-1(PS1) mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer’s disease (AD).

METHODS: The mice were allocated into the following nine groups: (a) the C57 Black (C57BL) sham-operated group (control group), (b) ischaemic treatment in C57BL mice (the C57 ischaemic group), (c) the APP/PS1 sham surgery group (APP/PS1 model group), (d) ischaemic treatment in APP/PS1 mice (APP/PS1 ischaemic group), (e) C57BL mice treated with aspirin following ischaemic treatment (C57BL ischaemic + aspirin group), (f) C57BL mice treated with SLT following ischaemic treatment (C57BL ischaemic + SLT group), (g) APP/PS1 mice treated with SLT (APP/PS1 + SLT group), (h) APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment (APP/PS1 ischaemic + donepezil hydrochloride group) and (i) APP/PS1 mice treated with SLT following ischaemic treatment (APP/PS1 ischaemic + SLT group). The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism. The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice. The hippocampus of each mouse was observed by haematoxylin and eosin (HE) and Congo red staining. The ultrastructure of NVUs in each group was observed by electron microscopy, and various biochemical indicators were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression level was detected by Western blot. The mRNA expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS: The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice, which were restored by SLT. The results of HE staining showed that SLT restored the pathological changes of the NVUs. The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex and hippocampus of the APP/PS1 and APP/PS1 ischaemic mice. Furthermore, SLT significantly reduced the content of Aβ, improved the vascular endothelium and repaired the mitochondrial structures. The ELISA detection, western blot detection and qRT-PCR showed that SLT significantly increased the vascular endothelial growth factor (VEGF), angiopoietin and basic fibroblast growth factor, as well as the levels of gene and protein expression of low-density lipoprotein receptor-related protein-1 (LRP-1) and VEGF in brain tissue.

CONCLUSIONS: By increasing the expression of VEGF, SLT can promote vascular proliferation, up-regulate the expression of LRP-1, promote the clearance of Aβ and improve the cognitive impairment of APP/PS1 mice. These results confirm that SLT can improve AD by promoting vascular proliferation and Aβ clearance to protect the function of NVUs.

Key words： Alzheimer disease; amyloid beta-protein precursor; presenilin-1; mice, transgenic; replenishing Qi and activating blood; neurovascular unit; Sailuotong

Cite this article

Linjuan SUN , Chengfu LI , Jiangang LIU , Nannan LI , Fuhua HAN , Dandan QIAO , Zhuang TAO , Min ZHAN , Wenjie CHEN , Xiaohui ZHANG , Chenguang TONG , Dong CHEN , Jiangxia Qi , Yang LIU , Xiao LIANG , Xiaoying ZHENG , Yunling ZHANG . Efficacy of Sailuotong (塞络通) on neurovascular unit in amyloid precursor protein/presenilin-1 transgenic mice with Alzheimer’s disease[J]. Journal of Traditional Chinese Medicine, 2024 , 44(2) : 289 -302 . DOI: 10.19852/j.cnki.jtcm.20240203.007

References

1. Tripathi SM, Murray AD. Alzheimer's dementia: the emerging role of positron emission tomography. Neuroscientist 2022; 28: 507-19.
2. Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer's disease. Lancet 2021; 397: 1577-90.
3. Button EB, Robert J, Caffrey TM, et al. Hdl from an Alzheimer’s disease perspective. Curr Opin Lipidol 2019; 30: 224-34.
4. Lane CA, Hardy J, Schott JM. Alzheimer's disease. Eur J Neurol 2018; 25: 59-70.
5. Fan L, Mao C, Hu X, et al. New insights into the pathogenesis of Alzheimer’s disease. Front Neurol 2019; 10: 1312.
6. Jean L, Foley AC, Vaux DJT. The physiological and pathological implications of the formation of hydrogels, with a specific focus on amyloid polypeptides. Biomolecules 2017; 7: 70.
7. Dauberman WN, Xu S. Alzheimer's disease pathogenesis: the denied access model. OMICS International 2017; 7: 1-10.
8. Kocahan S, Do?an Z. Mechanisms of Alzheimer’s disease pathogenesis and prevention: The brain, neural pathology, n-methyl-d-aspartate receptors, tau protein and other risk factors. Clin Psychopharmacol Neurosci 2017; 15: 1-8.
9. Carvey PM, Hendey B, Monahan AJ. The blood-brain barrier in neurodegenerative disease: a rhetorical perspective. J Neurochem 2009; 111: 291-314.
10. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 2011; 12: 723-38.
11. Ouellette J, Lacoste B. From neurodevelopmental to neurodegenerative disorders: the vascular continuum. Front Aging Neurosci 2021; 13: 749026.
12. Chen CL, Young SH, Gan HH, et al. Chinese medicine neuroaid efficacy on stroke recovery: a double-blind, placebo-controlled, randomized study. Stroke 2013; 44: 2093-100.
13. Wu B, Liu M, Liu H, et al. Meta-analysis of traditional chinese patent medicine for ischemic stroke. Stroke 2007; 38: 1973-9.
14. Yao W, Yang H, Ding G. Mechanisms of Qi-blood circulation and Qi deficiency syndrome in view of blood and interstitial fluid circulation. J Tradit Chin Med 2013; 33: 538-44.
15. Zhang Y, Liu J, Yao M, et al. Sailuotong capsule prevents the cerebral ischaemia-induced neuroinflammation and impairment of recognition memory through inhibition of lcn2 expression. Oxid Med Cell Longev 2019; 2019: 8416105.
16. Shi L, Zheng C, Shen Y, et al. Optical imaging of metabolic dynamics in animals. Nat Commun 2018; 9: 2995.
17. Obafemi TO, Owolabi OV, Omiyale BO, et al. Combination of donepezil and gallic acid improves antioxidant status and cholinesterases activity in aluminum chloride-induced neurotoxicity in wistar rats. Metab Brain Dis 2021; 36: 2511-9.
18. Lian W, Jia H, Xu L, et al. Multi-protection of dl0410 in ameliorating cognitive defects in d-galactose induced aging mice. Front Aging Neurosci 2017; 9: 409.
19. Chung CY, Licznerski P, Alavian KN, et al. The transcription factor orthodenticle homeobox 2 influences axonal projections and vulnerability of midbrain dopaminergic neurons. Brain 2010; 133: 2022-31.
20. Li P, Lu M, Shi J, et al. Lung mesenchymal cells elicit lipid storage in neutrophils that fuel breast cancer lung metastasis. Nat Immunol 2020; 21: 1444-55.
21. Wang J, Sun BL, Xiang Y, et al. Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in app/ps1 mice. Transl Psychiatry 2020; 10: 230.
22. Wang Z, Liu CY, Zhao Y, Dean J. Figla, lhx8 and sohlh1 transcription factor networks regulate mouse oocyte growth and differentiation. Nucleic Acids Res 2020; 48: 3525-41.
23. Kou J, Yang J, Lim JE, et al. Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer’s disease: prophylactic and therapeutic applications. Mol Neurobiol 2015; 51: 43-56.
24. Kaczmarczyk A, Hempel AM, Von Arx C, et al. Precise timing of transcription by c-di-gmp coordinates cell cycle and morphogenesis in caulobacter. Nat Commun 2020; 11: 816.
25. Guttenplan KA, Weigel MK, Adler DI, et al. Knockout of reactive astrocyte activating factors slows disease progression in an als mouse model. Nat Commun 2020; 11: 3753.
26. Reiss AB, Arain HA, Stecker MM, Siegart NM, Kasselman LJ. Amyloid toxicity in Alzheimer’s disease. Rev Neurosci 2018; 29: 613-27.
27. O'brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci 2011; 34: 185-204.
28. Jia J, Wei C, Chen S, et al. Efficacy and safety of the compound chinese medicine sailuotong in vascular dementia: a randomized clinical trial. Alzheimers Dement (N Y) 2018; 4: 108-17.
29. Steiner GZ, Yeung A, Liu JX, et al. The effect of sailuotong (slt) on neurocognitive and cardiovascular function in healthy adults: a randomised, double-blind, placebo controlled crossover pilot trial. BMC Complement Altern Med 2016; 16: 15.
30. Vickrey BG, Brott TG, Koroshetz WJ. Research priority setting:a summary of the 2012 ninds stroke planning meeting report. Stroke 2013; 44: 2338-42.
31. Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron 2017; 96: 17-42.
32. Echeverria V, Barreto GE, Avila-Rodriguezc M, Tarasov VV, Aliev G. Is vegf a key target of cotinine and other potential therapies against alzheimer disease? Curr Alzheimer Res 2017; 14: 1155-63.
33. Li W, Li P, Hua Q, et al. The impact of paracrine signaling in brain microvascular endothelial cells on the survival of neurons. Brain Res 2009; 1287: 28-38.
34. Religa P, Cao R, Religa D, et al. Vegf significantly restores impaired memory behavior in Alzheimer’s mice by improvement of vascular survival. Sci Rep 2013; 3: 2053.
35. Patel P, Shah J. Role of vitamin d in amyloid clearance via lrp-1 upregulation in Alzheimer’s disease: a potential therapeutic target? J Chem Neuroanat 2017; 85: 36-42.
36. Donahue JE, Flaherty SL, Johanson CE, et al. Rage, lrp-1, and amyloid-beta protein in Alzheimer’s disease. Acta Neuropathol 2006; 112: 405-15.
Options
Outlines

/

〈 〉