Abstract
AIM: This study aims to systematically evaluate and synthesize preclinical evidence on the neuroprotective effects of Triptolide (Tri) in Alzheimer's disease (AD) models, focusing on its impact on amyloid-beta accumulation, synaptic dysfunction, neuroinflammation, oxidative stress, autophagy, and apoptosis. INTRODUCTION: AD is the most common cause of dementia, yet current treatments largely target symptoms rather than underlying pathology. Tri, a bioactive compound from Tripterygium wilfordii, has shown promise due to its anti-inflammatory, antioxidant, and neuroprotective properties. METHODS: A systematic search of PubMed, Embase, and Web of Science was conducted up to 16 March 2024. English-language in vivo and in vitro studies on Tri's effects in AD models were included. Methodological quality was assessed using SYRCLE and SciRAP tools. The review is registered in PROSPERO (CRD42024521822). RESULTS: Out of 403 studies, 15 met the inclusion criteria (6 in vivo, 8 in vitro, 1 both). Tri reduced Aβ burden, enhanced memory and synaptic integrity, suppressed neuroinflammation and oxidative stress, and modulated autophagy and apoptosis. CONCLUSION: Tri demonstrates significant multi-target neuroprotective effects in AD preclinical models. Further high-quality studies are warranted to optimize dosing, delivery, and safety for clinical translation.