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Article

Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4

1
Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan
2
Departmental of Biomedical Science and Environmental Biology, Kaoshiung Medical University, Kaoshiung 80708, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 530; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030530
Received: 23 December 2018 / Revised: 14 January 2019 / Accepted: 24 January 2019 / Published: 27 January 2019
Serine protease dipeptidyl peptidase 4 (DPP-4) is involved in self/non-self-recognition and insulin sensitivity. DPP-4 inhibitors are conventional choices for diabetic treatment; however, side effects such as headache, bronchus infection, and nasopharyngitis might affect the daily lives of diabetic patients. Notably, natural compounds are believed to have a similar efficacy with lower adverse effects. This study aimed to validate the DPP-4 inhibitory activity of clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) from Polyalthia longifolia, rutin, quercetin, and berberine, previously selected through molecular docking. The inhibitory potency of natural DPP-4 candidates was further determined by enzymatic, in vitro Caco-2, and ERK/PKA activation in myocyte and pancreatic cells. The hypoglycemic efficacy of the natural compounds was consecutively analyzed by single-dose and multiple-dose administration in diet-induced obese diabetic mice. All the natural-compounds could directly inhibit DPP-4 activity in enzymatic assay and Caco-2 inhibition assay, and HCD showed the highest inhibition of the compounds. HCD down-regulated LPS-induced ERK phosphorylation in myocyte but blocked GLP-1 induced PKA expression. For in vivo tests, HCD showed hypoglycemic efficacy only in single-dose administration. After 28-days administration, HCD exhibited hypolipidemic and hepatoprotective efficacy. These results revealed that HCD performed potential antidiabetic activity via inhibition of single-dose and long-term administrations, and could be a new prospective anti-diabetic drug candidate. View Full-Text
Keywords: dipeptidyl peptidase 4; hyperglycemia; natural compound inhibitors; molecular docking; clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide dipeptidyl peptidase 4; hyperglycemia; natural compound inhibitors; molecular docking; clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide
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MDPI and ACS Style

Huang, P.-K.; Lin, S.-R.; Riyaphan, J.; Fu, Y.-S.; Weng, C.-F. Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4. Int. J. Mol. Sci. 2019, 20, 530. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030530

AMA Style

Huang P-K, Lin S-R, Riyaphan J, Fu Y-S, Weng C-F. Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4. International Journal of Molecular Sciences. 2019; 20(3):530. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030530

Chicago/Turabian Style

Huang, Po-Kai, Shian-Ren Lin, Jirawat Riyaphan, Yaw-Syan Fu, and Ching-Feng Weng. 2019. "Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4" International Journal of Molecular Sciences 20, no. 3: 530. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030530

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