Triptolide preserves cognitive function and reduces hippocampal inflammation in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that affects an estimated 50 million people worldwide. This remains a significant medical challenge. Despite the availability of numerous therapeutic agents, they are often only partially effective, highlighting the urgent need for the development of more effective next-generation drugs. Triptolide (T10), a key bioactive compound found in traditional Chinese medicine, is renowned for its wide range of pharmacological properties, including promising neuroprotective effects observed in vitro. However, its therapeutic effects and underlying mechanisms in the 5xFAD mouse model, particularly regarding microglial-mediated neuroinflammation, remain incompletely characterized. This study explored the impact of peripherally administered T10 on AD-associated behaviors and neuroinflammation in 5xFAD mice. The findings indicate that a 45-day T10 regimen significantly improved cognitive impairment in mice. Immunohistochemical analyses further demonstrated that T10 treatment markedly decreased Iba1-positive cell density in the CA1 region of the hippocampus and reduced immune and inflammatory responses in this region. Transcriptomic profiling suggests that T10 modulates cognitive function in 5xFAD mice via inflammatory signaling pathways. Taken together, these results suggest that T10 improves learning and cognitive performance and reduces hippocampal inflammatory responses in 5xFAD mice, supporting its further investigation as a potential therapeutic intervention for AD.