Huang-Pu-Tong-Qiao Formula Ameliorates the Hippocampus Apoptosis in Diabetic Cognitive Dysfunction Mice by Activating CREB/BDNF/TrkB Signaling Pathway

Shu Ye; Dao-Jun Xie; Peng Zhou; Hua-Wu Gao; Meng-Ting Zhang; Da-Bao Chen; Yun-Peng Qin; Xin Lei; Xin-Quan Li; Juan Liu; Ya-Xun Cheng; Yong-Chuan Yao; Biao Cai; Guo-Ming Shen

doi:10.1155/2021/5514175

Huang-Pu-Tong-Qiao Formula Ameliorates the Hippocampus Apoptosis in Diabetic Cognitive Dysfunction Mice by Activating CREB/BDNF/TrkB Signaling Pathway

Evid Based Complement Alternat Med. 2021 Jun 9:2021:5514175. doi: 10.1155/2021/5514175. eCollection 2021.

Authors

Shu Ye^{1

2

3}, Dao-Jun Xie⁴, Peng Zhou^{1

2

5}, Hua-Wu Gao^{1

2}, Meng-Ting Zhang^{1

2}, Da-Bao Chen^{1

3}, Yun-Peng Qin^{1

3}, Xin Lei^{1

3}, Xin-Quan Li^{1

3}, Juan Liu^{1

3}, Ya-Xun Cheng^{1

3}, Yong-Chuan Yao⁴, Biao Cai^{1

2

5}, Guo-Ming Shen^{1

2

3}

Affiliations

¹ School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China.
² Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei 230012, Anhui Province, China.
³ Graduate School of Anhui, Anhui University of Chinese Medicine, Hefei 230012, Anhui, China.
⁴ The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, Anhui Province, China.
⁵ Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei 230012, Anhui Province, China.

Abstract

Background: Huang-Pu-Tong-Qiao formula (HPTQ), a traditional Chinese medicine (TCM) formula used to improve cognitive impairment. However, the underlying neuroprotective mechanism of HPTQ treated for diabetic cognitive dysfunction (DCD) remains unclear. The purpose of this study was to investigate the neuroprotective mechanism of HPTQ in DCD mice based on molecular docking.

Methods: To investigate the neuroprotective effect of HPTQ in DCD, the Morris water maze (MWM), novel object recognition (NOR) test was used to detect the learning and memory changes of mice; hematoxylin-eosin (HE) staining was used to investigate the damage of hippocampal neurons; the western blot (WB) was used to examine the level of brain-derived neurotrophic factor (BDNF) of hippocampus. To investigate the neuroprotective mechanism of HPTQ in DCD, molecular docking was used to predict the possible target proteins of different active components in HPTQ and then the WB was used to verify the expression of key target proteins in the hippocampus of mice.

Results: HPTQ improved the learning and memory ability, hippocampal neuron damage, and the level of BDNF in the hippocampus of the DCD model treated with HFD/STZ for 12 weeks. Besides, the results of molecular docking showed that the main chemical components of HPTQ could be well combined with the targets of Bcl-2-associated X (Bax) and B-cell lymphoma2 (Bcl-2) and caspase-3. The levels of Bax/Bcl-2 protein ratio and caspase-3 increased in the DCD model while the HPTQ inhibited it. In addition, HPTQ restored DCD-induced decline of p-CREB, BDNF, TrkB, and p-Akt in the hippocampus.

Conclusions: These data indicated that HPTQ ameliorates the hippocampus apoptosis in diabetic cognitive dysfunction mice by activating CREB/BDNF/TrkB signaling pathway.