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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 (A?) and presence of hyperphosphorylated tau (p-tau) are hallmarks of AD, spreading in the region where insulin receptors are also found. A? exerts neuron toxicity, and could disturb insulin signaling of phosphatidylinositol 3-kinase (PI3K), glycogen synthase kinase (GSK)-3? 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 A? 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 A?-induced neuron apoptosis. F1 attenuate A?-induced caspase 3 expression especially at 25 ?g/mL, while F2 attenuate caspase 3 activation even at the low dose of 1 ?g/mL. Both AE subfractions decrease A?-enhanced DPP-4, but increase A?-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 A?-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-3?. This implies AE subfractions act on different targets, and could be developed respectively. In conclusion, we demonstrate AE is potential to prevent A?-induced neuron damage by regulating DPP-4 and the insulin resistance cascades. AE could be an adjuvant to protect neuron degenerative disease related to A? and insulin resistance.

SUBMITTER: Huang CN

PROVIDER: S-EPMC6592593 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Huang Chien-Ning CN Wang Chau-Jong CJ Lin Chih-Li CL Yen An-Ting AT Li Hsin-Hua HH Peng Chiung-Huei CH

PloS one 20190625 6

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 ...[more]

PMID: 31237881

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Project description:Nonalcoholic fatty liver disease (NAFLD) is recognized as the liver component of metabolic syndrome. The regulation of hepatic lipid should be emphasized to prevent accompanying illness. As AMP-activated protein kinase (AMPK) and sterol regulatory element binding protein (SREBP) regulate lipid metabolism, CD36 and fatty acid synthase (FAS) promote lipid uptake and lipogenesis respectively, while acetyl-CoA carboxylase (ACC) is an indicator of negative feedback. The increase of IRS-1 phosphorylation at the residue ser307 (p-ser307-IRS-1) and decrease of p-ser473-Akt (p-Akt) are viewed as the insulin resistance markers, and our previous reports suggested dipeptidyl peptidase-4 (DPP-4) mediates insulin resistance, the crucial factor of metabolic syndrome. Abelmoschus esculentus (AE) fruit is well-known for its antidiabetic utility. We had isolated several AE subfractions by successive steps, and found that F1 and F2 were especially valid in suppressing DPP-4 signaling. Since little is known if AE works on NAFLD, now we first attempt to investigate whether AE is useful to attenuate hepatic lipogenesis and lipid uptake in liver cells, along with improving the metabolic targets. We demonstrated that AE subfractions attenuated the hepatic lipid accumulation induced by free fatty acids. Treatment of AE alleviated FAS and returned the level of p-ser79-ACC (p-ACC). Although F1 was more effective on AMPK, F2 seemed more stable to attenuate SREBP-1. Moreover, as fatty acids stimulated the expression of CD36, F2 showed a superior effect to down-regulate the lipid uptake. Both AE subfractions reduced the generation of ROS, decreased the level of p-ser307-IRS-1, and restored the expression of p-Akt. Moreover, treatment of DPP-4 inhibitor linagliptin revealed that, AE could prevent the hepatic lipogenesis, oxidative burden, and the related insulin resistance via downregulating DPP-4. In conclusion, the present investigation revealed that AE, especially F2, is potential to be developed as adjuvant to prevent NAFLD.

Dataset Information

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

Publications

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

Similar Datasets

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