In the present study, in vitro, in vivo, and in silico models were used to evaluate the therapeutic potential of Pulmeria alba methanolic (PAm) extract, and we identified the major phytocompound,
apigetrin. Our in vitro studies revealed dose-dependent increased
glucose uptake and inhibition of α-
amylase (50% inhibitory concentration (IC50)= 217.19 µg/mL),
antioxidant (DPPH, ferric-reducing activity of plasma (FRAP), and lipid peroxidation (LPO) [IC50 = 103.23, 58.72, and 114.16 µg/mL respectively]), and anti-inflammatory potential (stabilizes human red blood cell (HRBC) membranes, and inhibits
proteinase and protein denaturation [IC50 = 143.73, 131.63, and 198.57 µg/mL]) by the PAm extract. In an in vivo model, PAm treatment reversed
hyperglycemia and attenuated
insulin deficiency in rats with
streptozotocin (STZ)-induced diabetes. A post-treatment tissue analysis revealed that PAm attenuated neuronal oxidative stress, neuronal
inflammation, and neuro-cognitive deficiencies. This was evidenced by increased levels of
antioxidants enzymes (
superoxide dismutase (SOD),
catalase (CAT), and
reduced glutathione (GSH)), and decreased
malondialdehyde (MDA), proinflammatory markers (
cyclooxygenase 2 (COX2), nuclear factor (NF)-κB and
nitric oxide (NOx)), and
acetylcholinesterase (AChE) activities in the brain of PAm-treated rats compared to the STZ-induced diabetic controls. However, no treatment-related changes were observed in levels of
neurotransmitters, including
serotonin and
dopamine. Furthermore, STZ-induced
dyslipidemia and alterations in serum
biochemical markers of hepatorenal dysfunction were also reversed by PAm treatment. Extract characterization identified
apigetrin (retention time: 21,227 s, 30.48%, m/z: 433.15) as the major bioactive compound in the PAm extract. Consequently, we provide in silico insights into the potential of
apigetrin to target AChE/COX-2/NOX/NF-κB Altogether the present study provides preclinical evidence of the therapeutic potential of the
apigetrin-enriched PAm extract for treating oxidative stress and neuro-
inflammation associated with diabetes.