Berberine and N-Acetylcysteine ameliorate diabetes-induced hippocampal damage by inhibiting apoptosis and neuroinflammation, and improve synaptic plasticity in rats.

Diabetes Mellitus (DM) is a metabolic disease characterized by hyperglycemia resulting from impaired insulin secretion and resistance. Berberine (BBR) and N-acetylcysteine are anti-inflammatory and antiapoptotic compounds that have beneficial effects on diabetic complications. This study aimed to investigate the effects of BBR and NAC on the Hippocampus in an experimental diabetes model in rats. Rats were divided into 5 groups: control, diabetes (D), D + NAC, D + BBR, and D + BBR + NAC. STZ (45 mg/kg, i.p.) was administered to the other four groups except the control group. BBR and NAC (50 mg/kg/day) were given intragastrically (i.g.) to the treatment groups for 28 days. Decreased cell body size, pyknotic cells and necrotic neurons were observed in the D group. However, these pathological changes were largely improved in the D + BBR, D + NAC, and D + BBR + NAC. Stereologically, there was no significant difference between the groups in terms of hippocampus volume. The number of pyramidal neurons in CA1 was significantly decreased in the D group. But the number of CA1 pyramidal neurons was higher in both the alone and combined BBR and NAC treatment groups than in the D group. Expressions of Caspase-3, TNF-α, and IL-1β increased in the D group, while expressions of Bcl-2 and SYP decreased. But, BBR and NAC treatments decreased Caspase-3, TNF-α, and IL-1β expressions and increased Bcl-2 and SYP expressions. These results revealed that BBR and NAC can have an antidiabetic effect against the neuronal damage caused by diabetes in the hippocampus CA1 region, suppressing inflammation and apoptosis and preventing the decrease in the number of pyramidal neurons. Also, they reveal that they may modulate synaptic plasticity by increasing synaptophysin expression.