Yang_2025_J.Microbiol.Biotechnol_35_e2412026

Zizania latifolia and its bioactive compound tricin have been recognized for their anti-inflammatory, anti-allergic, and anti-aging properties. However, the impact of Z. latifolia extract (ZLE) and tricin on astrocyte dysfunction, particularly related to disruptions in the amyloid beta (Abeta) clearance pathway, has not been extensively studied. This research aims to explore the regulatory effects of ZLE and tricin on astroglial dysfunction, utilizing astrocytic differentiated C6 cells (passages 75~85) subjected to Abeta and high-dose insulin, as well as scopolamine-induced mice. Results revealed that ZLE (500 microg/ml) and tricin (1 microg/ml) significantly upregulated the expression of astrocyte proteins GFAP and AQP4, brain-derived neurotrophic factor (BDNF), low-density lipoprotein receptor-related protein 1 (LRP1), and matrix metalloproteinases (MMPs) in C6 cells treated with Abeta and high-dose insulin. Furthermore, oral administration of ZLE (100 and 300 mg/kg) and tricin (0.3 mg/kg) in mice led to an increase in acetylcholine (ACh) levels and upregulation of insulin-degrading enzyme (IDE), LRP1, and MMPs, while reducing the levels of acetylcholinesterase (AChE), Abeta and ApoE4. These findings suggest that ZLE and tricin may ameliorate Abeta and high-dose insulin-induced astrocyte dysfunction in C6 cells and scopolamine-treated mice, potentially through the AQP4/LRP1 pathway.