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

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. Graphical abstract 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

The protective effects of sesamol and/or the probiotic, Lactobacillus rhamnosus, against aluminum chloride-induced neurotoxicity and hepatotoxicity in rats: Modulation of Wnt/β-catenin/GSK-3β, JAK-2/STAT-3, PPAR-γ, inflammatory, and apoptotic pathways

“…In addition, previous reports highlighted the potential of certain Lactobacillus strain supplementation as a probiotic in the regulation of emotional behavior in stress-related disorders (Bravo et al, 2011;Karen et al, 2021). Downregulation of the Wnt signaling balance has been interconnected with the development of Al-induced neurotoxicity (Mohamed et al, 2022). Therefore, upregulation of the Wnt signaling pathway prevents the cytotoxic effects of the accumulated Aβ (Toledo and Inestrosa, 2010).…”

The clinical efficacy of Olibanum gum chewing in patients with Mild‐to‐Moderate Alzheimer disease: A randomized Parallel‐Design controlled trial

“…In addition, anti-inflammatory effects of B. elongate have been frequently reported. [28][29][30][31] The resin of Boswellia serrata has shown a beneficial effect on treatment of inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, bronchial asthma osteoarthritis, and Frankincense Placebo chronic colitis. 26 More than 200 constituents of Olibanum may be responsible for therapeutic properties against inflammatory diseases 32 .…”

“…Methanol extract of the resin of B. carterii exhibited marked anti‐inflammatory activity for their inhibitory effect against 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced inflammation in mice. In addition, anti‐inflammatory effects of B. elongate have been frequently reported 28‐31 …”

“…In addition, anti‐inflammatory effects of B. elongate have been frequently reported. 28 , 29 , 30 , 31 …”

Water extract of frankincense and myrrh inhibits liver cancer progression and epithelial‑mesenchymal transition through Wnt/β‑catenin signaling

“…Acetyl-11-keto-β-boswellic acid (an active component of FM) can effectively inhibit the Wnt/β-catenin signaling pathway in mouse intestinal tumors, thereby inhibiting the proliferation and metastasis of mouse intestinal cancer cells (20). To the best of our knowledge, however, in HCC, there are few reports about FM and Wnt signaling (13,21).…”