Progress in the Treatment of Alzheimer’s Disease with Osthole

Abstract

As a progressive neurodegenerative disorder, Alzheimer’s disease is characterized by complex pathogenic mechanisms and a lack of effective therapeutic options, and has become a global public health challenge. Most current mainstream therapeutic agents target a single pathological process, with limited efficacy and frequent adverse effects. Consequently, identifying multi-target, low-toxicity active compounds from traditional Chinese medicine has emerged as an important research direction. Osthole, the major coumarin monomer component of Cnidium monnieri (L.) Cuss., exhibits multiple pharmacological activities, including neuroprotection, anti-inflammatory and antioxidant effects, as well as modulation of the cholinergic system. However, its specific mechanisms of action, efficacy, and safety in the treatment of Alzheimer’s disease have not yet been systematically summarized and elucidated. This paper aims to systematically review recent preclinical and clinical research progress on osthole in the treatment of Alzheimer’s disease, with a particular focus on its regulatory effects on key pathological processes such as β-amyloid protein deposition, Tau hyperphosphorylation, neuroinflammation, oxidative stress, and synaptic dysfunction. Existing evidence indicates that osthole can reduce Aβ production by inhibiting β-secretase activity, enhance autophagic clearance of abnormal proteins, attenuate neuroinflammation by suppressing excessive microglial activation, and improve mitochondrial function to counteract oxidative damage. In animal models, it has also been shown to ameliorate cognitive and memory impairments. These findings preliminarily reveal the potential of osthole to intervene in the pathological progression of Alzheimer’s disease via multiple pathways and targets, providing important experimental evidence and theoretical support for the development of novel Alzheimer’s disease therapies based on single compounds derived from traditional Chinese medicine, and laying a solid foundation for future in-depth studies on its pharmacodynamics, pharmacokinetics, and clinical applications.