Background
Insulin resistance could be associated with the development of Alzheimer disease (AD). The neuropathological hallmarks of AD are beta amyloid (Aβ) produced from sequential cleavage initiated by β-secretase and degraded by insulin degradation enzyme (IDE), as well as hyperphosphorylation of tau (p-tau). Insulin action involves the cascades of insulin receptor substrates (IRS) and phosphatidylinositol 3-kinase (PI3K), while phosphorylation of IRS-1 at ser307 (p-ser307IRS-1) hinders the response. Our previous report suggested dipeptidyl peptidase-4 (DPP-4) is crucial to insulin resistance, and the subfractions of Abelmoschus esculentus (AE), F1 and F2, attenuate the signaling. Here we
Conclusions
In conclusion, we demonstrated that AE would be a potential adjuvant to prevent insulin resistance and the associated pathogenesis of AD, and F2 seems more feasible to be developed.
Methods
The subfractions F1 and F2 were prepared according to a succession of procedures. F1 was composed by quercetin glycosides and triterpene ester, and F2 contained a large amount of polysaccharides. The in vitro insulin resistance model was established by SK-N-MC cell line treated with palmitate. MTT was used to define the dose range, and thereby Western blot, ELISA, and the activity assay were used to detect the putative markers. One-way ANOVA was performed for the statistical analysis.
Results
Treatment of palmitate induced the level of p-ser307IRS-1. Both F1 and F2 effectively decrease p-ser307IRS-1, and recover the expression of p-PI3K. However, the expression of total IRS plunged with 25 μg/mL of F1, while descended steadily with 5 μg/mL of F2. As palmitate increased the levels of Aβ40 and Aβ42, both AE subfractions were effective to reduce Aβ generation of and β-secretase activity, but IDE was not altered in any treatment conditions. The expression of DPP4 was also accompanied with insulin resistance signals. Inhibition of DPP4 attenuated the activity of β-secretase and production of Aβ. Moreover, the present data revealed that both AE subfractions significantly decrease the level of p-Tau. Conclusions: In