Hypoglycemic effect and mechanism of honokiol on type 2 diabetic mice

Abstract

BackgroundHonokiol 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.MethodsType 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.ResultsIn 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.ConclusionThese 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.

Honokiol Restores Polymyxin Susceptibility to MCR-1-Positive Pathogens both In Vitro and In Vivo

“…Fortunately, recent research has shown that new dosage forms of honokiol were developed to improve its solubility and bioavailability without toxic side effects, making it better for clinical use (35,36). It was reported that mice were orally administered 200 mg/kg honokiol for 8 weeks without any toxicity and with good tolerance and high median lethal dose safety (25). In addition, intravenous administration of 20 to 80 mg/kg in rats showed no significant difference in serum biochemical parameters or histopathological changes in the rats (37).…”

“…Here, our study found a natural compound, honokiol [3=,5-di-(2-propenyl)-1,1=biphenyl-2,4=-diol], which is mainly derived from the dry skin and the root bark and branch bark of Magnolia officinalis, to be an effective MCR-1 inhibitor. Honokiol performs various pharmacological functions, including anti-inflammatory, antiulcer, antioxidation, anti-aging, antitumor, and cholesterol-lowering activities, and it displays significant protection of the central nervous system (22)(23)(24)(25)(26). As yet, there has been no report of honokiol as an inhibitor of resistant enzymes.…”

Honokiol induces reactive oxygen species-mediated apoptosis in Candida albicans through mitochondrial dysfunction

“…Honokiol, a phenolic compound, has been isolated from the bark of the Magnolia officinalis tree. It has been used in traditional Chinese medicine due to its potent properties, which include anti-hyperglycemic [ 12 ], anti-depressant [ 13 ], anti-tumor [ 14 ], and anti-inflammatory abilities [ 15 ]. Previous work from our lab has shown that honokiol can inhibit adhesion, transition from yeast to hypha, and biofilm formation in C .…”

Honokiol induces superoxide production by targeting mitochondrial respiratory chain complex I in Candida albicans

“…Honokiol, a neolignan isolated from the oriental medicine plant Magnolia officinalis , is an interesting compound exhibiting various pharmacological activities in preclinical experimental models [ 10 – 14 ]. Honokiol molecule contains two phenolic groups which can exhibit antioxidant properties similar to vitamin E or polyphenols.…”