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

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

Research on Evaluation Index System of Scientific and Technological Achievements in Traditional Chinese Medicine Clinical Research

Background The effective evaluation of scientific and technological achievements in traditional Chinese medicine (TCM) is of great significance in promoting the innovative development of TCM. Previous evaluations of scientific and technological achievements in TCM often used a generalized evaluation method, leading to problems such as inappropriate indicators and limited dimensions, which is not conducive to reflecting the multiple values of achievements in a scientific and comprehensive way. Consequently, there is an urgent need to establish categorized and multi-dimensional evaluation index system for the evaluation of scientific and technological achievements in TCM in the new period. Objective To establish a scientific, categorized, reliable and comprehensive evaluation index system that reflects the principles of TCM and highlights its unique advantages aiming at the scientific and technological achievements in TCM, in accordance with the contemporary requirements for scientific and technological evaluation in China. Methods This study began in November 2022 and was completed in May 2023. A preliminary index framework was developed through literature review and focus group discussions. Delphi expert consultation was then conducted over two rounds to determine the evaluation indexes and points. The hierarchical analysis method was used to calculate the weight of each index. Results The final evaluation index system of scientific and technological achievements in TCM clinical research comprised 10 threshold indicators, 4 primary indicators, 17 secondary indicators, and 17 evaluation points. After testing, the positive coefficient of experts in both rounds of Delphi method implementation was 100%, the authority coefficient was 0.94 and 0.93, respectively. The Kendall's W consistency test for each level of indicators yielded two-tailed significance (P<0.05), indicated high levels of expert positivity and authority, strong consistency of expert opinion, and reliable consulting results. Conclusion This study constructs a scientific, reasonable, reliable and easy-to-operate evaluation index system for scientific and technological achievements in TCM clinical research. The indexes cover a wide range with highly differentiated weights and TCM characteristics, which is conducive to highlighting the core strengths while comprehensively considering the multiple value of the results. Additionally, the associated evaluation points, enhancing the operationalization of the index system, may potentially serve as a valuable reference for related evaluation activities