Huang-Pu-Tong-Qiao Formula Ameliorates Tau Phosphorylation by Inhibiting the CaM-CaMKIV Pathway

Shu Ye; Biao Cai; Peng Zhou; Guoquan Wang; Huawu Gao; Rupeng Hua; Liangzhen You; Yongchuan Yao; Yan Wang; Guoming Shen

doi:10.1155/2020/8956071

Huang-Pu-Tong-Qiao Formula Ameliorates Tau Phosphorylation by Inhibiting the CaM-CaMKIV Pathway

Evid Based Complement Alternat Med. 2020 May 11:2020:8956071. doi: 10.1155/2020/8956071. eCollection 2020.

Authors

Shu Ye^{1

2}, Biao Cai^{1

2

3}, Peng Zhou^{1

2

3}, Guoquan Wang¹, Huawu Gao^{1

2}, Rupeng Hua¹, Liangzhen You¹, Yongchuan Yao⁴, Yan Wang^{1

2}, Guoming Shen^{1

2}

Affiliations

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

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disease. It is a chronic, lethal disease in which brain function is severely impaired and neuronal damage is irreversible. Huang-Pu-Tong-Qiao (HPTQ), a formula from traditional Chinese medicine, has been used in the clinical treatment of AD for many years, with remarkable effects. However, the neuroprotective mechanisms of HPTQ in AD have not yet been investigated. In the present study, we used AD models in vivo and in vitro, to investigate both the neuroprotective effect of HPTQ water extracts (HPTQ-W) and the potential mechanisms of this action. For the in vivo study, after HPTQ intervention, the Morris water maze test was used to examine learning and memory in rats. Transmission electron microscopy and immunofluorescence methods were then used to investigate neuronal damage. For the in vitro experiments, rat primary hippocampal neurons were cultured and cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Additionally, mRNA levels of CaM, CaMKK, CaMKIV, and tau were examined using qRT-PCR, and protein expression of CaM, CaMKK, p-CaMKIV, and p-tau were examined using western blot. In vivo, we revealed that HPTQ significantly improved learning and memory deficits and attenuated neuronal damage in the AD rat model. Furthermore, in vitro results showed that HPTQ significantly increased cell viability in the AD cell model. We also demonstrated that HPTQ significantly decreased the mRNA levels of CaM, CaMKK, CaMKIV, and tau and significantly decreased the protein expressions of CaM, CaMKK, p-CaMKIV, and p-tau. In conclusion, our results indicated that HPTQ improved cognition and ameliorated neuronal damage in AD models and implicated a reduction in tau phosphorylation caused by inhibition of the CaM-CaMKIV pathway as a possible mechanism.