2. Academic Validation
  3. Huang-Pu-Tong-Qiao Formula Alleviates Hippocampal Neuron Damage by Inhibiting NLRP3 Inflammasome-mediated Pyroptosis in Alzheimer's Disease

Huang-Pu-Tong-Qiao Formula Alleviates Hippocampal Neuron Damage by Inhibiting NLRP3 Inflammasome-mediated Pyroptosis in Alzheimer's Disease

  • Mol Neurobiol. 2024 Oct 28. doi: 10.1007/s12035-024-04547-0.
Nan Shao # 1,  Zhixian Ding # 1,  Fei Liu # 1,  Xiaoyan Zhang 1,  Xiaojuan Wang 1,  Shenglin Hu 1 2 3 4,  Shu Ye 1 2 3 4,  Tingting Wang 1 2 3 4,  Wenwen Si 5 6 7 8,  Biao Cai 9 10 11 12
Affiliations

Affiliations

  • 1 College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012, China.
  • 2 Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, China.
  • 3 Key Laboratory of Xin'an Medicine, Anhui University of Chinese Medicine, Ministry of Education, Hefei, 230012, China.
  • 4 Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, 230012, China.
  • 5 College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012, China. siwenwen2008@163.com.
  • 6 Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, China. siwenwen2008@163.com.
  • 7 Key Laboratory of Xin'an Medicine, Anhui University of Chinese Medicine, Ministry of Education, Hefei, 230012, China. siwenwen2008@163.com.
  • 8 Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, 230012, China. siwenwen2008@163.com.
  • 9 College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012, China. caibiao@ahtcm.edu.cn.
  • 10 Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, China. caibiao@ahtcm.edu.cn.
  • 11 Key Laboratory of Xin'an Medicine, Anhui University of Chinese Medicine, Ministry of Education, Hefei, 230012, China. caibiao@ahtcm.edu.cn.
  • 12 Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, 230012, China. caibiao@ahtcm.edu.cn.
  • # Contributed equally.
PMID: 39466576 DOI: 10.1007/s12035-024-04547-0
Abstract

Huang-Pu-Tong-Qiao (HPTQ), a Traditional Chinese Medicine formula, has achieved remarkable efficacy in clinically treating Alzheimer's disease (AD). Pyroptosis refers to the inflammatory necrosis of cells, which contributes to AD pathological progression. However, it is unclear whether the therapeutic effect of HPTQ on AD is related to reducing Pyroptosis. In this study, the network pharmacology analysis was used to predict the molecular mechanism of HPTQ in treating AD and validated our hypothesis through mice and cell experiments. APP/PS1 transgenic mice and Aβ25-35-injured HT22 cells were used as AD models in vivo and in vitro. The pharmacological effects and mechanisms of HPTQ on AD were evaluated by Morris water maze, Y-maze, transmission electron microscope, immunofluorescence, Hoechst/PI staining, western blot, and ELISA. Network pharmacology reveals the correlation between the therapeutic effect of HPTQ on AD and the NOD-like Receptor signaling pathway. In APP/PS1 mice, HPTQ reduced the escape latency and maintained cell membrane integrity. In HT22 cells, 15% HPTQ-medicated serum and 10 µM MCC950 increased cell viability and decreased PI positive rate compared with the Model group. In addition, HPTQ treatment in AD animal and cell models reduced the protein expressions of NLRP3, ASC, cleaved Caspase-1, GSDMD, GSDMD-N, IL-1β, and IL-18. The experimental results of MCC950 specifically inhibiting the NLRP3 expression suggested that HPTQ might reduce neuronal Pyroptosis by reducing NLRP3 inflammasome. Network pharmacology and experimental validation suggested that HPTQ alleviated NLRP3 inflammasome-mediated neuronal Pyroptosis in AD, which could provide valuable candidate drugs for AD clinical treatment.

Keywords

Alzheimer’s disease; Huang-Pu-Tong-Qiao; NLRP3 inflammasome; Network pharmacology; Pyroptosis; Traditional Chinese medicine.

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