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Hypoglycemic effect and mechanism of honokiol on type 2 diabetic mice

Authors Sun J, Fu X, Liu Y, Wang Y, Huo B, Guo Y, Gao X, Li W, Hu X

Received 21 July 2015

Accepted for publication 15 September 2015

Published 4 December 2015 Volume 2015:9 Pages 6327—6342


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Wei Duan

Jing Sun,1 Xueqi Fu,1–3 Ye Liu,1 Yongsen Wang,1 Bo Huo,1 Yidi Guo,1 Xuefeng Gao,1 Wannan Li,1–3,* Xin Hu1–3,*

1School of Life Sciences, 2Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, 3National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China

*These authors contributed equally to this work

Background: Honokiol is one of the main bioactive constituents of the traditional Chinese herbal drug Magnolia bark (Cortex Magnoliae officinalis, Hou Po). The aim of this study was to probe its anti-type 2 diabetes mellitus effects and the underlying mechanism.
Methods: Type 2 diabetic mouse model was established by intraperitoneally injecting with streptozotocin. Fasting blood glucose, body weight, and lipid profile were measured. The subcutaneous adipose tissue, skeletal muscle, and liver were isolated as well as homogenized. The phospho-insulin receptor β-subunit (IRβ), IRβ, phospho-AKT, AKT, phospho-ERK1/2, ERK1/2, phosphotyrosine, and actin were examined by Western blot assay. Cell viability or cytotoxicity was analyzed by using MTT method. The inhibitory potencies of honokiol on the protein tyrosine phosphatase 1B (PTP1B) activity were performed in reaction buffer. Molecular docking and dynamic simulation were also analyzed.
Results: In in vivo studies, oral treatment with 200 mg/kg honokiol for 8 weeks significantly decreases the fasting blood glucose in type 2 diabetes mellitus mice. The phosphorylations of the IRβ and the downstream insulin signaling factors including AKT and ERK1/2 significantly increase in adipose, skeletal muscle, and liver tissue of the honokiol-treated mice. Moreover, honokiol enhanced the insulin-stimulated phosphorylations of IRβ, AKT, and ERK1/2 in a dose-dependent manner in C2C12 myotube cells. Meanwhile, honokiol enhanced insulin-stimulated GLUT4 translocation. Importantly, honokiol exhibited reversible competitive inhibitory activity against PTP1B with good selectivity in vitro and in vivo. Furthermore, using molecular docking and dynamic simulation approaches, we determined the potential binding mode of honokiol to PTP1B at an atomic level.
Conclusion: These findings indicated the hypoglycemic effects of honokiol and its mechanism that honokiol improved the insulin sensitivity by targeting PTP1B. Therefore, our study may highlight honokiol as a promising insulin sensitizer for the therapy of type 2 diabetes.

Keywords: honokiol, T2DM, insulin sensitizer, PTP1B

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