Zhi-Shi-Wu-Huang attenuates amyloid beta toxicity in Caenorhabditis elegans Alzheimer's disease models via modulating insulin DAF-16 signaling pathway

Alzheimers disease (AD) is a common neurodegenerative disorder primarily caused by Amyloid-beta (A{beta}) toxicity. Therefore, there is an urgent need to develop novel, effective, and safe drugs to treat AD. Traditional Chinese Medicine (TCM) has a long history of use in protecting against memory impairments. Recently, TCM has attracted growing attention from researchers as a source of potent neuroprotective compounds. In this study, we focus on four TCM herbs with multiple therapeutic properties: Valeriana jatamansi (V; 20 mg/mL), Acori tatarinowii (A; 10 mg/mL), Fructus Schisandrae (F; 5 mg/mL), and Scutellaria baicalensis (S; 2.5 mg/mL). The aim is to develop a neuroprotective anti-AD formulation, named "Zhi-Shi-Wu-Huang" derived from V, A, F, and S, and evaluate its efficacy in transgenic Caenorhabditis elegans models of AD. These four TCM herbs are among the most potent activators of the HSP-70 promoter, promoting the expression of heat shock protein 70 (HSP-70), which helps prevent protein misfolding and aggregation. Additionally, V, A, F, S, and the Zhi-Shi-Wu-Huang formula were found to reduce reactive oxygen species (ROS) production and enhance the expression of superoxide dismutase-3 (sod-3) and chymotrypsin-like proteasomes. Our findings demonstrate that both the individual extracts (V, A, F, S) and the Zhi-Shi-Wu-Huang formulation significantly reduce A{beta}-induced toxicity in transgenic worms by activating the insulin/DAF-16 signaling pathway.