The association between diabetes and
dementia has been well demonstrated by epidemiologic studies.
Berberine (BBR) has been reported to ameliorate diabetes and
diabetic encephalopathy (DE). However, the mechanism is still unknown. In this study, we employ a diabetic model, db/db mice, to explore whether BBR could protect DE through the
SIRT1/endoplasmic reticulum (ER) stress pathway. Behavioral results (Morris water maze, Y-maze spontaneous alternation test, and fear conditioning test) showed that
oral administration of BBR (50 mg/kg) improved the learning and memory ability. Furthermore, BBR promoted lipid metabolism and decreased fasting
glucose in db/db mice. Moreover, western blot analysis revealed that BBR increased the synapse- and nerve-related
protein expression (PSD95, SYN, and
NGF) and decreased the
protein expression of inflammatory factors (TNF-α and NF-κB) in the hippocampus of db/db mice. BBR also increased the
protein expression of
SIRT1 and downregulated ER stress-associated
proteins (PERK, IRE-1α, eIF-2α, PDI, and CHOP) in the hippocampus of db/db mice. Taken together, the present results suggest that the
SIRT1/ER stress pathway might be a crucial mechanism in the
neuroprotective effect of BBR against DE.