Abelmoschus esculentus Improves Hippocampal Function Associated with Dipeptidyl Peptidase-4 in High Fat Diet-Fed db/db Mice

Hippocampal function can be impaired by diabetes mellitus (DM) and obesity. Abelmoschus esculentus (AE) fractions reportedly mitigate the symptoms of Alzheimer's disease (AD) by downregulating dipeptidyl peptidase-4 (DPP-4)-mediated insulin resistance. AE extracted by alcohol (fraction 1, F1) and water (fraction 2, F2) contained quercetin glycosides and polysaccharides, respectively. In this study, we investigated whether AE affects hippocampal function in in vitro and in vivo systems. Our results indicate that F1 or F2 enhanced neurogenesis and synapse formation in palmitate-treated hippocampal neural cells, presumably by downregulating DPP-4. In db/db mice fed with high fat diet, the hippocampal insulin resistance correlated spatial recognition, with fraction F2 improving hippocampal function. Of note, the alteration of neurogenesis seems interconnecting with changes in gut microbiota. In summary, AE can improve hippocampal function, attenuate insulin resistance, and promote neurogenesis by regulating DPP-4. AE, particularly F2, has the potential to serve as an adjuvant in preventing DM-associated AD.