Chinese medicine monomers in the treatment of Alzheimer’s disease: Some preclinical findings

• DOI: 10.1002/alz.063031
• Publication Date: 2023-06-16T10:06:46Z
• Authors: Jianping Jia; Yan Li; Diyang Lyu; Haishan Jiao; Yuqing Shi; Meina Quan
• Keywords: Hyperphosphorylation

Abstract Background Most of the FDA approved drugs for AD are symptom driven and effects limited. Because is a complex disease involving multiple pathological changes, such as senile plaques formed by amyloid‐β (Aβ) deposition, neurofibrillary tangles caused tau hyperphosphorylation, microglia‐evoked neuroinflammation, synaptic degeneration, blood‐brain barrier (BBB) disruption. While current anti‐dementia mostly single targets, Chinese medicines have great development potential considering their multi‐target components. Method Several medicine monomers, including cryptotanshinone (CTS), pterostilbene (PTE), Ginsenoside Compound K (GCK), glabridin (Gla) were selected to test safety efficacy in cell models, further explore possible molecular mechanisms target action. Aβ42 oligomers (AβO) used establish models. The cytotoxicity AβO well protective monomers on models evaluated using MTT assay. pathways tested qRT‐PCR, ELISA, Western blot immunofluorescence. Result induced injury, apoptosis, generation intracellular reactive oxygen species (ROS). In AβO‐induced CTS significantly reduced hyperphosphorylation at Ser202, Ser404, Thr181, Thr231, increased levels PSD95 synaptophysin; PTE attenuated ROS generation; GCK diminished inflammatory cytokine production; Gla injury (figure1). Further study found that action include PI3K/Akt/GSK3β pathway (figure2), BBB permeability tight junction scaffold protein (figure3), NF‐kB via LRP1 activation (figure4), respectively. Conclusion These results provides rational basis therapeutic application treatment AD, support evaluation these treatment.