Abelmoschus esculentus subfractions attenuate beta amyloid-induced neuron apoptosis by regulating DPP-4 with improving insulin resistance signals.

Abstract

The association of Alzheimer disease (AD) and Diabetes (DM) is less clear. Accumulation of beta amyloid (Aβ) and presence of hyperphosphorylated tau (p-tau) are hallmarks of AD, spreading in the region where insulin receptors are also found. Aβ exerts neuron toxicity, and could disturb insulin signaling of phosphatidylinositol 3-kinase (PI3K), glycogen synthase kinase (GSK)-3β and AMP-activated protein kinase (AMPK), but increase IRS-1-Ser307 phosphorylation which is viewed as insulin resistance marker. Previously we reported dipeptidyl peptidase-4 (DPP-4) mediate insulin resistance signals, and Abelmoschus esculentus (AE) subfractions F1 (rich in quercetin glucosides and triterpene ester) and F2 (containing large amount of polysaccharides) attenuate DPP-4-mediated apoptosis. In the present study, we aim to investigate if Aβ induce neuron death by regulating DPP-4 and insulin resistance signals, and the putative effect of F1 and F2. By MTT, microscopy, and Western blotting, we demonstrate treatment of appropriate doses of AE subfractions prevent Aβ-induced neuron apoptosis. F1 attenuate Aβ-induced caspase 3 expression especially at 25 μg/mL, while F2 attenuate caspase 3 activation even at the low dose of 1 μg/mL. Both AE subfractions decrease Aβ-enhanced DPP-4, but increase Aβ-reduced p-AMPK and p-PI3K. The activity analysis reveals that F2 is more valid than F1 to reduce DPP-4 activity. The inhibition of DPP-4 demonstrates it plays the pivotal role in Aβ-induced neuron apoptosis. Moreover, although both F1 and F2 are effective to inhibit p-IRS-1-Ser307, F2 takes advantage to reduce p-Tau while F1 is superior to enhance p-GSK-3β. This implies AE subfractions act on different targets, and could be developed respectively. In conclusion, we demonstrate AE is potential to prevent Aβ-induced neuron damage by regulating DPP-4 and the insulin resistance cascades. AE could be an adjuvant to protect neuron degenerative disease related to Aβ and insulin resistance.

• Authors: Chien-Ning Huang, Chau-Jong Wang, Chih-Li Lin, An-Ting Yen, Hsin-Hua Li, Chiung-Huei Peng
• Journal: PloS one (PLoS One) Vol. 14 Issue 6 Pg. e0217400 ( 2019) ISSN: 1932-6203 [Electronic] United States
• PMID: 31237881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Plant Extracts
• AMP-Activated Protein Kinases
• DPP4 protein, human
• Dipeptidyl Peptidase 4

Topics

• AMP-Activated Protein Kinases (metabolism)
• Abelmoschus (chemistry)
• Alzheimer Disease (drug therapy, metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Apoptosis (drug effects)
• Cell Line
• Diabetes Mellitus (drug therapy, metabolism, pathology)
• Dipeptidyl Peptidase 4 (metabolism)
• Humans
• Insulin Resistance
• Neurons (metabolism, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Plant Extracts (chemistry, pharmacology)
• Signal Transduction (drug effects)