Trichosanthis Semen Exerts Neuroprotective Effects in Alzheimer’s Disease Models by Inhibiting Amyloid-β Accumulation and Regulating the Akt and ERK Signaling Pathways

Background: Alzheimer’s disease (AD), the most common form of dementia, is characterized by memory loss and the abnormal accumulation of senile plaques composed of amyloid-β (Aβ) protein. Trichosanthis Semen (TS) is a traditional herbal medicine used to treat phlegm-related conditions. While TS is recognized for various bioactivities, including anti-neuroinflammatory effects, its ability to attenuate AD remains unknown. Objective: To evaluate the effects of TS extract (TSE) on neuronal damage, Aβ accumulation, and neuroinflammation in AD models. Methods: Thioflavin T and western blot assays were used to assess effects on Aβ aggregation in vitro. TS was treated to PC12 cells with Aβ to assess the neuroprotective effects. Memory functions and histological brain features were investigated in TSE-treated 5×FAD transgenic mice and mice with intracerebroventricularly injected Aβ. Results: TSE disrupted Aβ aggregation and increased the viability of cells and phosphorylation of both protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) in vitro. TSE treatment also suppressed the accumulation of Aβ plaques in the brain of 5×FAD mice, protected neuronal cells in both the subiculum and medial septum, and upregulated Akt/ERK phosphorylation in the hippocampus. Moreover, TSE ameliorated the memory decline and glial overactivation observed in 5×FAD mice. As assessing whether TS affect Aβ-induced neurotoxicity in the Aβ-injected mice, the effects of TS on memory improvement and neuroinflammatory inhibition were confirmed. Conclusions: TSE disrupted Aβ aggregation, protected neurons against Aβ-induced toxicity, and suppressed neuroinflammation, suggesting that it can suppress the development of AD.