• Ershiwuwei Zhenzhu pills may be a potential candidate against Alzheimer’s disease. • Ershiwuwei Zhenzhu pills alleviated amyloid-β induced paralysis in Caenorhabditis elegans. • Component of water extract of Ershiwuwei Zhenzhu pills was identified using UPLC-Q-TOF-MS/MS. • Ershiwuwei Zhenzhu pills increased the expression of daf-16, skn-1 and bec-1. Alzheimer’s disease (AD) is the most common form of dementia which burdens patients’ family and society heavily. However, no effective cure for AD was proposed. Ershiwuwei Zhenzhu pills (EZP) is a kind of traditional Tibetan medicine formulation with a wide range of clinical uses. An increasing number of research demonstrates that EZP possesses neuroprotective, anti-inflammatory and antioxidant effect, suggesting that EZP could be a potential candidate against AD. This study was conducted with the aim to identify the components in the water extract of EZP (WE-EZP) and validate the effect of WE-EZP against amyloid-β (Aβ) induced toxicity in transgenic Caenorhabditis elegans ( C. elegans ) AD model. We evaluated the effect against Aβ-induced toxicity of six EZP extracts using the C. elegans AD‐like model CL4176 and CL2355. To investigate the impact on Aβ expression, transgenic worms CL2006 and qRT-PCR were applied. Network pharmacology was utilized to find out the possible mechanism and qRT-PCR was used for validation. By screening from six extracts of EZP, the WE-EZP showed prominent effect in delaying Aβ-induced paralysis within the range of 1-6 mg/mL. This effect was further identified in CL2355. WE-EZP treatment significantly reduced the number of amyloid deposits in a dose-dependent manner and decreased the expression level of Aβ mRNA. Analysis of network pharmacology indicated that EZP may alleviate Aβ-induced toxicity by regulating antioxidant system and autophagy. Further study showed that WE-EZP may exert effect against Aβ-induced toxicity by up-regulating daf-16, skn-1, and bec-1. In conclusion, this study provided experimental evidence supporting the neuroprotective potential of WE-EZP against Aβ toxicity, primarily through the modulation of stress-response and autophagy pathways. Further investigations are warranted to identify the precise bioactive compounds and to validate the efficacy in mammalian models.
Wang et al. (Sun,) studied this question.