Arctium lappa L. Leaves Alleviate Alzheimer's Disease-Like Pathologies by Modulating the Tricarboxylic Acid Cycle and Inhibiting STAT3/NF-кB Signaling.

Current drugs for Alzheimer's disease (AD) have limited efficacy and often cause adverse side effects. Burdock leaves, known for their heat-clearing and anti-inflammatory properties, can be consumed as a vegetable or brewed into tea. According to traditional Chinese medicine, heat-clearing and anti-inflammatory strategies are considered beneficial for the treatment of AD. Nevertheless, it remains unclear whether burdock leaves have neuroprotective effects or can alleviate neuroinflammation to delay AD progression. Herein, we found that the decline in learning and memory, as well as cognitive impairments in AD model rats, were significantly improved following burdock leaf intervention. Notably, the medium- and high-dose groups showed superior therapeutic outcomes compared to the low-dose group. Histopathological analysis of rat hippocampal tissue revealed that burdock leaves mitigated hippocampal lesions, neuronal loss, pathological amyloid β-protein accumulation, and abnormal phosphorylation of the microtubule-associated Tau protein. Metabolomics studies identified the tricarboxylic acid (TCA) cycle as a key metabolic pathway modulated by burdock leaves in AD regulation. Western blot analysis revealed that the therapeutic effects of burdock leaves may be mediated through the suppression of the STAT3/NF-κB signaling pathway and downregulation of inflammatory protein expression. Of note, the present study uncovered that burdock leaves could delay AD progression by ameliorating metabolic dysregulation and inhibiting STAT3/NF-κB-mediated inflammatory pathways, positioning them as a promising candidate for further exploration in AD therapeutics.