Magnolia officinalisExtract Contains Potent Inhibitors against PTP1B and Attenuates Hyperglycemia in db/db Mice

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is an established therapeutic target for type 2 diabetes mellitus (T2DM) and obesity. The aim of this study was to investigate the inhibitory activity of Magnolia officinalis extract (ME) on PTP1B and its anti-T2DM effects. Inhibition assays and inhibition kinetics of ME were performed in vitro. 3T3-L1 adipocytes and C2C12 myotubes were stimulated with ME to explore its bioavailability in cell level. The in vivo studies were performed on db/db mice to probe its anti-T2DM effects. In the present study, ME inhibited PTP1B in a reversible competitive manner and displayed good selectivity against PTPs in vitro. Furthermore, ME enhanced tyrosine phosphorylation levels of cellular proteins, especially the insulin-induced tyrosine phosphorylations of insulin receptor β-subunit (IRβ) and ERK1/2 in a dose-dependent manner in stimulated 3T3-L1 adipocytes and C2C12 myotubes. Meanwhile, ME enhanced insulin-stimulated GLUT4 translocation. More importantly, there was a significant decrease in fasting plasma glucose level of db/db diabetic mice treated orally with 0.5 g/kg ME for 4 weeks. These findings indicated that improvement of insulin sensitivity and hypoglycemic effects of ME may be attributed to the inhibition of PTP1B. Thereby, we pioneered the inhibitory potential of ME targeted on PTP1B as anti-T2DM drug discovery.

Hypoglycemic effect and mechanism of honokiol on type 2 diabetic mice

“…C2C12 myoblasts culture and differentiation were performed as our previously published. 13 In brief, C2C12 myoblasts were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM), supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin (PS) at 37°C in humidified atmosphere with 5% CO 2 . For differentiation, C2C12 myoblasts were cultured to 75% confluence in DMEM with 10% FBS, 1% PS.…”

“…12 In our previous study, we validated the antidiabetic activity of Magnolia bark. 13 Honokiol is proved to be the pharmacologically effective component 12 with the potent activity of antioxidant, anti-inflammatory, antibacterial, antitumor, and antianxiety antithrombotic. 14 – 17 Recently, Atanasov et al 18 demonstrated that honokiol functions as a novel nonadipogenic partial PPAR-γ activator in vitro.…”

Extracts of Magnolia Species-Induced Prevention of Diabetic Complications: A Brief Review

“…Using a type 2 diabetes (T2DM) mouse model established by high-fat diet (HFD) combining with streptozotocin (STZ) injection, Sun et al [17] demonstrated that oral gavage of honokiol at dose of 200 mg/kg once per day for 8 weeks significantly decreased the blood glucose levels. Sun et al [5] also investigated the effect of Magnolia officinalis extract on blood glucose level of db/db mice which have been recognized as a model of T2DM. The authors found that Magnolia extracts (ME) treatment once a day at dose of 0.5 g/kg for 4 weeks attenuates hyperglycemia in db/db mice.…”

“…Sun et al [5] demonstrated that in vitro treatment with Magnolia officinalis extracts enhanced the phosphorylation of insulin receptor β-subunit (IRβ) in response to insulin stimulation in 3T3-L1 adipocytes and C2C12 myotubes by suppressing the activity of protein tyrosine phosphatases 1B, which finally resulted in enhanced insulin-stimulated glucose transporter 4 (GLUT4) translocation and extracellular signal-regulated kinases phosphorylation. Furthermore, it has been reported that honokiol can act as an agonist of peroxisome proliferator-activated receptor gamma, which plays an important role in regulation of glucose homeostasis [14].…”

“…Many natural plants are known to have promising antidiabetic properties [1,2,3,4]. For example, bioactive constituents of Magnolia attenuated hyperglycemia [5], prevented cardiac pathogenesis [6] and live damage [7] and histologic renal damage [8] in diabetes and obesity.…”