Abelmoschus esculentus subfractions attenuate Aß and tau by regulating DPP-4 and insulin resistance signals.
BMC Complement Med Ther
; 20(1): 370, 2020 Dec 02.
Article
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| MEDLINE
| ID: mdl-33267804
ABSTRACT
BACKGROUND:
Insulin resistance could be associated with the development of Alzheimer disease (AD). The neuropathological hallmarks of AD are beta amyloid (Aß) produced from sequential cleavage initiated by ß-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 aim to investigate whether AE works to reduce Aß generation via regulating DPP4 and insulin resistance.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 Aß40 and Aß42, both AE subfractions were effective to reduce Aß generation of and ß-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 ß-secretase and production of Aß. Moreover, the present data revealed that both AE subfractions significantly decrease the level of p-Tau.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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
/
Extractos Vegetales
/
Péptidos beta-Amiloides
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Proteínas tau
/
Dipeptidil Peptidasa 4
Límite:
Humans
País/Región como asunto:
Asia
Idioma:
En
Revista:
BMC Complement Med Ther
Año:
2020
Tipo del documento:
Article
País de afiliación:
Taiwán