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

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

doi:10.1155/2021/5514175

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.

Highlights

Diabetic cognitive dysfunction (DCD), a diabetic central nervous system (CNS) complication, is characterized by cognitive deficits, neurochemical electrophysiological neurostructural abnormalities [1,2,3]
The hippocampus involved in the pathophysiology of streptozocin (STZ) induced cognitive dysfunction [8, 9]. e loss of glucose levels in the hippocampus may lead to mitochondrial dysfunction, initiate apoptosis, and eventually lead to hippocampal neuron damage. e pathogenesis of diabetic cognitive dysfunction (DCD) is complex, including insulin signaling disorders, autonomic dysfunction, and neuroinflammatory pathway abnormalities, advanced glycation end products deposition, mitochondrial metabolism disorders, etc
Our previous studies have demonstrated that Huang-Pu-Tong-Qiao formula (HPTQ) could improve cognitive impairments of Alzheimer’s disease (AD) rats by inhibiting multiple pathways, including EGFR-PLCc, CaM-CaMKIV, oxidative stress, and mitochondrial apoptotic signaling pathways [11, 14]. e HPTQ could improve the apoptosis of primary hippocampal neurons induced by Aβ25-35 [15]

Summary

Introduction

Diabetic cognitive dysfunction (DCD), a diabetic central nervous system (CNS) complication, is characterized by cognitive deficits, neurochemical electrophysiological neurostructural abnormalities [1,2,3]. E purpose of this study was to investigate the neuroprotective mechanism of HPTQ in DCD mice based on molecular docking. 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; hematoxylineosin (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. 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. Ese data indicated that HPTQ ameliorates the hippocampus apoptosis in diabetic cognitive dysfunction mice by activating CREB/BDNF/TrkB signaling pathway Conclusions. ese data indicated that HPTQ ameliorates the hippocampus apoptosis in diabetic cognitive dysfunction mice by activating CREB/BDNF/TrkB signaling pathway

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Discussion

Conclusion