Screening and evaluation of Thai herbal plants as multifunctional agents for targeting amyloid β pathogenesis in Alzheimer's disease

Background: Alzheimer's disease (AD) is a neurodegenerative disorder driven by complex pathophysiological processes. Current therapeutic strategies emphasize the development of multifunctional agents, particularly those derived from natural sources, to target multiple stages of the amyloid β (Aβ) cascade, a central contributor to AD pathology. Objectives: This study aimed to investigate the anti-Aβ activity of nine Thai herbs and evaluate their potential as multifunctional agents for AD treatment. Methods: Nine Thai herbs—Caesalpinia sappan (CS), Thunbergia laurifolia (TL), Rhinacanthus nasutus (RN), Tabernaemontana divaricata (TD), Cyperus rotundus (CR), Terminalia chebula (TC), Azadirachta indica (AI), Piper retrofractum (PR), and Asparagus racemosus (AR)—were screened using a two-step in vitro testing system. Biochemical assays assessed Aβ aggregation and fibril disaggregation, while cell-based assays evaluated neuroprotective effects against Aβ-induced toxicity in SH-SY5Y neuroblastoma cells. The extracts’ impact on the expression of genes related to Aβ production (App, Bace1, Adam10) and clearance (Ide, Nep) was further analyzed. Results: Eight herbal extracts, excluding AR, inhibited Aβ aggregation and promoted Aβ fibril disaggregation. Among these, RN, TD, TC, and PR demonstrated significant neuroprotective effects in SH-SY5Y cells. Further evaluation revealed that PR reduced Aβ production by downregulating Bace1 and upregulating Adam10, while TC enhanced Aβ clearance by increasing Ide expression. Conclusion: PR and TC exhibited multifunctional anti-Aβ activities, highlighting their potential as promising candidates for developing anti-AD agents. These findings provide a foundation for future therapeutic development targeting AD pathology.