Boswellic acids ameliorate neurodegeneration induced by AlCl₃: the implication of Wnt/β-catenin pathway

Alzheimer's disease (AD) is a neurodegenerative disease (ND) that represents the principal cause of dementia. Effective treatment is still lacking. Without prevention, Alzheimer's disease (AD) incidence is expected to triple within 30 years. The risk increases in highly polluted areas and is positively linked to chronic aluminum (Al) exposure. Canonical Wingless-Int (Wnt)/β-catenin pathway has been found to play a considerable role in ND pathogenesis. Resins of Boswellia serrata (frankincense) have been used traditionally for their psychoactive activity, in addition to their memory-boosting effects. Boswellic acids (BA) are pentacyclic triterpenes. They have antioxidant, anti-inflammatory, antinociceptive, and immunomodulatory activities. This study aimed to elucidate the role of the Wnt/β-catenin pathway in BA protective activity against aluminum-induced Alzheimer's disease. For 6 weeks, rats were treated daily with AlCl3 (100 mg/kg/i.p.) either alone or with BA (125 or 250 mg/kg PO). Results indicated that BA significantly improved learning and memory impairments induced by AlCl₃ treatment. Moreover, BA treatment significantly decreased acetylcholinesterase levels and reduced amyloid-beta (Aβ) expression. In addition, BA ameliorated the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), inhibited lipid peroxidation, and increased total antioxidants in the brain. Indeed, BA significantly suppressed AlCl₃-induced decrease of brain-derived neurotrophic factor, pGSK-3β (Ser 9), and β-catenin. BA (250 mg/kg) showed a significant protective effect compared to a lower dose. The results conclude that BA administration modulated the expression of Wnt/β-catenin pathway-related parameters, contributing to BA's role against Al-induced Alzheimer's disease. Effect of Boswellic acids on AlCl₃-induced neurodegenerative changes. ChE cholinesterase, Ach acetylcholine, BDNF brain-derived neurotrophic factor, IL-1β interleukin-1β, TNF-α tumor necrosis factor-α.