Leaf Extract from Lithocarpus polystachyus Rehd. Promote Glycogen Synthesis in T2DM Mice

Abstract

The purpose of this study was to investigate the effects of leaf extract from Lithocarpus polystachyus Rehd. on type II diabetes mellitus (T2DM) and the active ingredients of this effect. In addition, this study determined, for the first time, the underlying molecular and pharmacological mechanisms of the extracts on hyperglycemia using long-term double high diet-fed and streptozotocin (STZ) induced type II diabetic mice. In the present study, leaf extract, phloridzin and trilobatin were assessed in vivo (gavage) and in vitro (non-invasive micro-test technique, NMT) in experimental T2DM mice. The biochemical parameters were measured including blood glucose and blood lipid level, liver biochemical indexes, and hepatic glycogen. The relative expression of glycometabolism-related genes was detected. The effect of leaf extracts on physiological glucose flux in liver tissue from control and T2DM mice was also investigated. Body weight of experimental T2DM mice increased significantly after the first week, but stabilized over the subsequent three weeks; body weight of all other groups did not change during the four weeks’ study. After four weeks, all treatment groups decreased blood glucose, and treatment with leaf extract had numerous positive effects: a) promoted in glucose uptake in liver, b) increased synthesis of liver glycogen, c) reduced oxidative stress, d) up-regulation of glucokinase (GK), glucose transporter 2 (GLUT2), insulin receptor (IR) and insulin receptor substrate (IRS) expression in liver, e) down-regulation of glucose-6-phosphatase (G-6-P) expression, and f) ameliorated blood lipid levels. Both treatment with trilobatin or phloridzin accelerated liver glycogen synthesis, decreased oxidative stress and increased expression of GK. IRS and phosphoenolpyruvate carboxykinase (PEPCK) were both up-regulated after treatment with trilobatin. Expression of GLUT2, PEPCK and G-6-P were also increased in liver tissue after treatment with phloridzin. Our data indicate that leaf extract from L. polystachyus Rehd. has a preferable hypoglycemic effects than trilobatin or phloridzin alone. Leaf extract significantly increased glucose uptake and hepatic glycogen synthesis while also inducing a decline of hepatic gluconeogenesis and oxidative stress in T2DM mice. From this study, we draw conclusions that L. polystachyus promoted glycogen synthesis in T2DM mice, and that the active compounds were not only the trilobatin or phloridzin.

Trilobatin Protects Against Oxidative Injury in Neuronal PC12 Cells Through Regulating Mitochondrial ROS Homeostasis Mediated by AMPK/Nrf2/Sirt3 Signaling Pathway

“…Trilobatin (TLB; Figure 1A ), a small molecule monomer, is considered as a novel bioactive compound of Lithocarpus polystachyus Rehd. Previous studies have demonstrated that TLB exhibited anti-oxidant and anti-inflammatory activities (Fan et al, 2015 ; Wang J. et al, 2016 ), but until now, the protective effect of TLB on oxidative stress-induced cellular mitochondrial dysfunction and apoptosis in neuron still remains a mystery. Under this scenario, the aim of this study was designed to assess whether TLB exerts salutary effects on H 2 O 2 -induced PC12 cell injury and its underlying mechanisms.…”

Cryoconcentration of flavonoid extract for enhanced biophotovoltaics and pH sensitive thin films

“…In addition to the proof of principle demonstrations herein, our previous work has shown that anthocyanin can be used to synthesize nanoparticles or for functional foods, and Castañeda‐Ovando et al discuss a variety of other applications such as cosmetic and pharmaceutical uses. We have shown the simple extraction and cryoconcentration of anthocyanin from B. oleracea using block cryoconcentration with partial gravitational thawing as an effective method for creating value added products.…”

“…4,5 Plants that are rich in anthocyanins include blueberries, raspberries, concord grapes, and red cabbage. 6 Anthocyanin extracts are used as food additives, 7,8 medicinal supplements, 9,10 molecular templates for nanomaterial synthesis, 11,12 various cosmetic applications, 13 dyesensitized solar cells, 14,15 and as biodetectors. 16,17 Due to the diverse applications of anthocyanins, research on the development of this value added agricultural product has increased in the last decade.…”

Trilobatin Ameliorates Insulin Resistance through IRS-AKT-GLUT4 Signaling Pathway in C2C12 Myotubes and ob/ob Mice

“…It has been shown that trilobatin has anti-oxidative 9,10 , anti-viral and anti-in ammatory activities 11,12 . Trilobatin also exhibits anti-hyperglycemic properties by accelerating liver glycogen synthesis, decreasing oxidative stress, increasing the expression of glucokinase, and up-regulating the expression of insulin receptor substrate (IRS) on long-term double high fat-diet and streptozotocin (STZ) induced type 2diabetic mice 13 . Similar to other dihydrochalcones, phlorizin (a dual SGLT1/SGLT2 inhibitor) 14 , phloretin (a GLUT2 inhibitor) 15 , and acarbose (an alpha-glucosidase inhibitor) 16,17 , our previous works demonstrated that trilobatin could be bind with SGLT1/2 18 .…”