Neuroprotective effects of Uncaria rhynchophylla alkaloid extracts against amyloid-β toxicity via regulation of oxidative stress pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla is a important medicinal plant in Chinese traditional medicine for the treatment of neurological disorders, its alkaloid-rich constituents are considered the primary bioactive components responsible for its effects on the central nervous system. AIM OF THE STUDY: This study aimed to investigate the neuroprotective effects of U. rhynchophylla alkaloid extract (URAs) against amyloid-β (Aβ)-induced neurotoxicity and oxidative stress, and elucidate underlying molecular mechanisms. MATERIALS AND METHODS: URAs was prepared and characterized by LC-MS/MS for chemical profiling. The neuroprotective effects were evaluated using transgenic C. elegans CL2006 and CL2355, and H2O2-induced PC12 cells. In C. elegans, paralysis assay, Aβ deposition, and chemotaxis behavior were assessed. Oxidative stress markers including reactive oxygen species (ROS), lipofuscin accumulation, lipid peroxidation (MDA), and antioxidant enzyme activities (SOD, CAT) were measured. Quantitative real-time PCR was performed to examine the expression of genes of related signaling pathways. In PC12 cells, cell viability, ATP levels, and oxidative stress were evaluated. RESULTS: URAs treatment significantly delayed Aβ-induced paralysis, reduced Aβ deposition, and improved chemotaxis behavior in transgenic C. elegans, while decreasing ROS, lipofuscin, and MDA, and increasing SOD and CAT activities. Furthermore, URAs modulated the expression of genes involved in Aβ metabolism, proteasome function, and antioxidant defense, and significantly suppressed the expression of p38 MAPK signaling pathway components. CONCLUSION: Our findings demonstrate that URAs exert neuroprotective effects against Aβ toxicity and oxidative stress through multi-target mechanisms involving enhanced antioxidant defense, regulated proteostasis, highlighting their therapeutic potential for AD intervention.