Advanced Search

Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 4: 759 - 769

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.04.006

Original Articles

Mechanism analysis of Tongqiao Yizhi decoction (通窍益智颗粒) in treating vascular dementia rats by brain tissue untargeted metabonomics and fecal 16S rRNA gene sequencing

  • Raoqiong WANG ,
  • Linyao HAO ,
  • Ye LU ,
  • Lingxue WANG ,
  • Jianrong LI ,
  • Yan PENG ,
  • Hongmei TANG ,
  • Shuangyang LI ,
  • Xue BAI
Expand
  • 1 Department of Neurology, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China
    2 Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, China
LI Shuangyang, Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China. lisy@swmu.edu.cn,Telephone: +86-13909081756; +86-18208350086
Prof. BAI Xue, Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China. baixue@swmu.edu.cn,

Received date: 2024-02-22

  Accepted date: 2024-08-28

  Online published: 2025-07-25

Supported by

Southwest Medical University Project: Exploring the Neuroprotective Mechanism of Tongqiao Yizhi Decoction on Vascular Dementia Rats Based on the Brain Gut Axis(southwest Medical University [2021] No. 1)

Fold

Abstract

OBJECTIVE: To analyze the mechanism of Tongqiao Yizhi decoction (TQYZD, 通窍益智颗粒) in treating vascular dementia (VaD) rats using brain tissue untargeted metabonomics and fecal 16S rRNA gene sequencing.

METHODS: The chemical composition of TQYZD was analyzed by ultra-high performance liquid chromatography-high resolution mass spectrometry. The effects of TQYZD on VaD rats were evaluated by water maze test, hematoxylin-eosin staining, enzyme-linked immunosorbent assay and Western blot. Untargeted metabolomics and 16S rRNA sequencing were utilized to explore the relationship between metabolic profiles and the structure and function of intestinal flora. Fecal microbiota transplantation (FMT) was used to validate the role of gut microbiota in VaD. Spearman correlation analysis of differential metabolites and gut microbiota was performed.

RESULTS: The results showed that TQYZD improved cognitive function and neuronal damage in VaD rats, and reduced inflammatory response and repaired the intestinal barrier. In addition, TQYZD had the effect of modulating gut microbes in VaD rats, and FMT further confirmed that gut flora plays an important role in TQYZD treatment of VaD. Untargeted metabolomics revealed that VaD could lead to metabolic disorders in brain tissues, and TQYZD significantly altered the metabolites of brain tissues in Middle Cerebral Artery Occlusion rats. The results of spearman correlation analysis showed that there was a significant correlation between intestinal flora and the metabolites of brain tissues.

CONCLUSION: In this study, we demonstrated that TQYZD can improve metabolic disorders in vascular dementia rats by acting on intestinal flora.

Key words： dementia, vascular; gastrointestinal microbiome; fecal microbiota transplantation; metabolomics; Tongqiao Yizhi decoctionSupporting information

Cite this article

Raoqiong WANG , Linyao HAO , Ye LU , Lingxue WANG , Jianrong LI , Yan PENG , Hongmei TANG , Shuangyang LI , Xue BAI . Mechanism analysis of Tongqiao Yizhi decoction (通窍益智颗粒) in treating vascular dementia rats by brain tissue untargeted metabonomics and fecal 16S rRNA gene sequencing[J]. Journal of Traditional Chinese Medicine, 2025 , 45(4) : 759 -769 . DOI: 10.19852/j.cnki.jtcm.2025.04.006

References

1. O'Brien JT, Thomas A. Vascular dementia. Lancet 2015; 386: 1698-706.
2. Smith EE. Clinical presentations and epidemiology of vascular dementia. Clin Sci (Lond) 2017; 131: 1059-68.
3. Korczyn AD, Vakhapova V, Grinberg LT. Vascular dementia. J Neurol Sci 2012; 322: 2-10.
4. Schneider E, O'Riordan KJ, Clarke G, Cryan JF. Feeding gut microbes to nourish the brain: unravelling the diet-microbiota-gut-brain axis. Nat Metab 2024; 6: 1454-78.
5. Ma Q, Xing C, Long W, Wang HY, Liu Q, Wang RF. Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis. J Neuroinflammation 2019; 16: 53.
6. Yang YF, Xu GY, Wang Q, et al. The effect of mangiferin on the structure and abundance of intestinal microbiota in mice. Xi Nan Yi Ke Da Xue Xue Bao 2023; 46: 344-9.
7. Antushevich H. Fecal microbiota transplantation in disease high-doseerapy. Clin Chim Acta 2020; 503: 90-8.
8. Tian Z, Liu J, Liao M, et al. Beneficial effects of fecal microbiota transplantation on ulcerative colitis in mice. Dig Dis Sci 2016; 61: 2262-71.
9. Meng S, Li S, Chen H, Deng C, Meng Z, Wang Y. Metabolomics deciphering high-dosee potential biomarkers of Hengqing I prescription against vascular dementia. Evid Based Complement Alternat Med 2022; 2022: 1636145.
10. Fleszar MG, Wi?niewski J, Zboch M, Diakowska D, Gamian A, Krzystek-Korpacka M. Targeted metabolomic analysis of nitric oxide/L-arginine pahigh-doseway metabolites in dementia: association wihigh-dose pahigh-doseology, severity, and structural brain changes. Sci Rep 2019; 9: 13764.
11. Jian WX, Zhang Z, Zhan JH. Donepezil attenuates vascular dementia in rats through increasing BDNF induced by reducing HDAC6 nuclear translocation. Acta Pharmacol Sin 2020; 41: 588-98.
12. Xu P, Liang L, Bai X. Clinical observation on the effect of modified Qufeng Tongqiao recipe on cognitive dysfunction after stroke. Shi Jie Zui Xin Yi Xue Xin Xi Wen Zhai 2019; 19: 16-7.
13. Ye LS, Bai X, Zhang DC. Observation on the effect of Qufeng Tongqiao recipe in the treatment of post circulatory transient ischemic attack. Zhong Guo Yi Liao Ji Qiu 2022; 31: 1415-8.
14. Ren JH, Xu P, Li SY, et al. The effect and mechanism of Tongqiao Yizhi granules on blood-brain barrier function and angiogenesis in vascular dementia rats. Xian Dai Zhong Xi Yi Jie He Za Ji 2022; 31: 3238-3245.
15. Li SY, Wang LX, Pu YT, Wang RQ, Tang HM, Bai X. Study on the effect of Tongqiao Yizhi Granule on apoptosis of hippocampal neurons in rats with vascular dementia through cAMP/PKA-CREB signal pathway. Zhong Yao Yao Li Yu Lin Chuang 2020; 36: 190-5.
16. Wang G, Zhao G, Chao X, Xie L, Wang H. The characteristic of virulence, biofilm and antibiotic resistance of Klebsiella pneumoniae. Int J Environ Res Public Health 2020; 17: 6278.
17. Yang Q, Wu SM, Wang CM, et al. Effects of decabromodiphenyl ether exposure on learning and memory and hippocampal NMDA receptors in rats. Xi Nan Yi Ke Da Xue Xue Bao 2022; 45: 211-6.
18. Borody TJ, Paramsothy S, Agrawal G. Fecal microbiota transplantation: indications, methods, evidence, and future directions. Curr Gastroenterol Rep 2013; 15: 337.
19. Djoumbou FY, Eisner R, Knox C. Classyfire: automated chemical classification with a comprehensive, computable taxonomy. J Cheminform 2016; 8: 61.
20. Lazarov O, Hollands C. Hippocampal neurogenesis: learning to remember. Prog Neurobiol 2016; 138-40: 1-18.
21. Georgy GS, Nassar NN, Mansour HA, Abdallah DM. Cerebrolysin ameloriates cognitive deficits in type Ⅲ diabetic rats. PLoS One 2013; 8: e64847.
22. Rosenberg GA. Extracellular matrix inflammation in vascular cognitive impairment and dementia. Clin Sci (Lond) 2017; 131: 425-37.
23. Skoog I, Korczyn AD, Guekht A. Neuroprotection in vascular dementia: a future path. J Neurol Sci 2012; 322: 232-6.
24. Wang HX, Wang YP. Gut microbiota-brain axis. Chin Med J (Engl) 2016; 129: 2373-80.
25. McDonald AJ, Mott DD. Functional neuroanatomy of amygdalohippocampal interconnections and their role in learning and memory. J Neurosci Res 2017; 95: 797-820.
26. Qiao L, Li B, Li Q. Effects of polygonum multiflorum on vascular dementia and IL-6, IL-8 and TNF- α Horizontal influence. Shangxi Zhong Yi 2018; 39: 1177-80.
27. Ohland CL, Kish L, Bell H. Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinology 2013; 38: 1738-47.
28. Huang HM, Wu XX, Wang Y, et al. Effects of excessive intake of free sugars on colitis mice and gut microbiota. Xi Nan Yi Ke Da Xue Xue Bao 2021; 44: 619-27.
29. Wang L, Yang JW, Lin LT. Acupuncture attenuates inflammation in microglia of vascular dementia rats by inhibiting miR-93-mediated low-doseR4/MyD88/NF-κB signaling pathway. Oxid Med Cell Longev 2020; 2020: 8253904.
30. Toombs-Ruane LJ, Benschop J, Burgess S, Priest P, Murdoch DR, French NP. Multidrug resistant enterobacteriaceae in New Zealand: a current perspective. N Z Vet J 2017; 65: 62-70.
31. Iljazovic A, Roy U, Gálvez EJC. Perturbation of the gut microbiome by Prevotella spp. enhances host susceptibility to mucosal inflammation. Mucosal Immunol 2021; 14: 113-24.
32. Zafar H, Saier MH. Gut Bacteroides species in health and disease. Gut Microbes 2021; 13: 1-20.
33. O'Callaghan J, O'Toole PW. Lactobacillus: host-microbe relationships. Curr Top Microbiol Immunol 2013; 358: 119-54.
34. Rocha-Ramírez LM, Pérez-solano RA, Casta?ón-Alonso SL, et al. Probiotic Lactobacillus strains stimulate the Inflammatory response and activate human macrophages. J Immunol Res 2017; 2017: 4607491.
35. Wu H, Xie S, Miao J. Lactobacillus reuteri maintains intestinal epithelial regeneration and repairs damaged intestinal mucosa. Gut Microbes 2020; 11: 997-1014.
36. Rudolphi KA, Schubert P. Modulation of neuronal and glial cell function by adenosine and neuroprotection in vascular dementia. Behav Brain Res 1997; 83: 123-8.
37. Du B, Zhang Y, Liang M. N6-methyladenosine (m6A) modification and its clinical relevance in cognitive dysfunctions. Aging (Albany NY) 2021; 13: 20716-37.
38. Rudman D, Mattson DE, Feller AG. Serum fatty acid profile of elderly tube-fed men in a nursing home. J Am Geriatr Soc 1989; 37: 229-34.
39. R?nnemaa E, Zethelius B, Vessby B, Lannfelt L, Byberg L, Kilander L. Fatty-acid composition and the risk of Alzheimer's disease: a longitudinal population-based study. Eur J Clin Nutr 2012; 66: 885-90.
40. Li CY, Zhang L, Li J. Effect of endogenous arginine-vasopressin arising from the paraventricular nucleus on learning and memory functions in vascular dementia model rats. Biomed Res Int 2017; 2017: 3214918.
Options
Outlines

/

〈 〉