Asiaticoside Mitigates Alzheimer’s Disease Pathology by Attenuating Inflammation and Enhancing Synaptic Function

Author:

Liu Sai12,Chen Long12,Li Jinran12,Sun Yuan12,Xu Yue3,Li Zhaoxing4,Zhu Zheying5ORCID,Li Xinuo12

Affiliation:

1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

2. Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

3. Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA

4. State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China

5. School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UK

Abstract

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder, hallmarked by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles. Due to the uncertainty of the pathogenesis of AD, strategies aimed at suppressing neuroinflammation and fostering synaptic repair are eagerly sought. Asiaticoside (AS), a natural triterpenoid derivative derived from Centella asiatica, is known for its anti-inflammatory, antioxidant, and wound-healing properties; however, its neuroprotective function in AD remains unclear. Our current study reveals that AS, when administered (40 mg/kg) in vivo, can mitigate cognitive dysfunction and attenuate neuroinflammation by inhibiting the activation of microglia and proinflammatory factors in Aβ1-42-induced AD mice. Further mechanistic investigation suggests that AS may ameliorate cognitive impairment by inhibiting the activation of the p38 MAPK pathway and promoting synaptic repair. Our findings propose that AS could be a promising candidate for AD treatment, offering neuroinflammation inhibition and enhancement of synaptic function.

Funder

Nature Science Foundation of Jiangsu Province

Postdoctoral Excellence Program of Jiangsu Province

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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