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

Environ Sci Pollut Res Int. 2022 Oct;29(50):76135-76143. doi: 10.1007/s11356-022-20611-5. Epub 2022 Jun 6.

Abstract

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.

Keywords: Aluminum toxicity; Alzheimer’s disease; Boswellic acids; Neurodegenerative diseases; Wnt/β-catenin.

MeSH terms

  • Acetylcholine / therapeutic use
  • Acetylcholine / toxicity
  • Acetylcholinesterase / metabolism
  • Aluminum / toxicity
  • Aluminum Chloride / toxicity
  • Alzheimer Disease* / drug therapy
  • Analgesics / toxicity
  • Animals
  • Anti-Inflammatory Agents
  • Antioxidants / metabolism
  • Boswellia*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Frankincense* / therapeutic use
  • Frankincense* / toxicity
  • Interleukin-1beta / metabolism
  • Neurodegenerative Diseases* / chemically induced
  • Neurodegenerative Diseases* / drug therapy
  • Pentacyclic Triterpenes / therapeutic use
  • Pentacyclic Triterpenes / toxicity
  • Rats
  • Triterpenes
  • Tumor Necrosis Factor-alpha / metabolism
  • beta Catenin / metabolism

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Antioxidants
  • Brain-Derived Neurotrophic Factor
  • Interleukin-1beta
  • Pentacyclic Triterpenes
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • beta Catenin
  • Aluminum Chloride
  • boswellic acid
  • Aluminum
  • Acetylcholinesterase
  • Acetylcholine
  • Frankincense