Therapeutic potential of bitter taste receptor agonists on amyloid β-induced rat model of Alzheimer’s disease

Abstract

ABSTRACT This study was conducted to investigate the effect of bitter taste receptor (T2R) agonists (caffeine and extracts of myrrh and Boswellia serrata) on amyloid β (Aβ)-induced Alzheimer’s disease (AD) in rats. Rats intracerebroventricularly (ICV) injected with a single dose of Aβ (3 μg/μL/rat) had significantly: 1) lower brain weight, 2) higher short-term memory impairment, 3) lower serum dopamine level, 4) higher AChE activity, 5) higher brain lipid peroxide malonaldehyde, 6) lower brain antioxidant activities of catalase, superoxide dismutase and glutathione peroxidase, 7) higher brain phosphor tau protein level, 8) higher brain levels of apoptotic markers (Bax and caspase 3), 9) lower brain level of antiapoptotic marker Bcl2, 10) downregulated brain expression of the bitter receptor (T2R4) gene, 11) upregulated brain expression of tumor necrosis factor α (TNFα) and nuclear factor κB (NF-κB) genes and 12) marked neuronal degeneration associated with severe vacuolation of neutrophils. All deteriorated effects of Aβ were restored following treatment with caffeine (20 mg/kg), myrrh aqueous extract (10 mg/kg) and Boswellia serrata aqueous extract (400 mg/kg) with best effect for myrrh aqueous extract. These data conclude that bitter taste receptor agonists (caffeine and extracts of myrrh and Boswellia serrata) had therapeutic potential on amyloid β-induced rat model of Alzheimer’s disease.