Anti-Hyperglycemic Effects of Refined Fractions from Cyclocarya paliurus Leaves on Streptozotocin-Induced Diabetic Mice.

Zheling Feng,Lishe Gan,Chi Teng Vong,Maggie Pui Man Hoi,Cheng Chen,Ligen Lin,Ruohan Lou,Jiali Chen,Zhujun Fang

doi:10.3390/molecules26226886

Abstract

To identify the chemical components responsible for the anti-hyperglycemic effect of Cyclocarya paliurus (Batal.) Iljinsk (Juglandaceae) leaves, an ethanol extract (CPE) and a water extract (CPW) of C. paliurus leaves, as well as their total flavonoids (CPF), triterpenoids (CPT) and crude polysaccharides (CPP), were prepared and assessed on streptozotocin (STZ)-induced diabetic mice. After being orally administrated once a day for 24 days, CPF (300 mg/kg), CPP (180 mg/kg), or CPF+CPP (300 mg/kg CPF + 180 mg/kg CPP) treatment reversed STZ-induced body weight and muscle mass losses. The glucose tolerance tests and insulin tolerance tests suggested that CPF, CPP, and CPF+CPP showed anti-hyperglycemic effect in STZ-induced diabetic mice. Furthermore, CPF enhances glucose-stimulated insulin secretion in MIN6 cells and insulin-stimulated glucose uptake in C2C12 myotubes. CPF and CPP suppressed inflammatory cytokine levels in STZ-induced diabetic mice. Additionally, CPF and CPP improved STZ-induced diabetic nephropathy assessed by H&E staining, blood urea nitrogen content, and urine creatinine level. The molecular networking and Emperor analysis results indicated that CPF showed potential anti-hyperglycemic effects, and HPLC–MS/MS analysis indicated that CPF contains 3 phenolic acids and 9 flavonoids. In contrast, CPT (650 mg/kg) and CPC (300 mg/kg CPF + 180 mg/kg CPP + 650 mg/kg CPT) did not show anti-hyperglycemic effect. Taken together, polysaccharides and flavonoids are responsible for the anti-hyperglycemic effect of C. paliurus leaves, and the clinical application of C. paliurus need to be refined.

Highlights

Diabetes mellitus is increasing at an alarming rate worldwide, especially in developing countries [1,2]
The body weight from the STZ group of mice was significantly decreased in comparison to that of the control group (Figure 1B); 25 days treatment of CPP + mg/kg CPT (CPC) or CPT slightly reversed body weight loss compared to the STZ group, and treatment of C. paliurus leaves. Total flavonoids (CPF), C. paliurus polysaccharides (CPP), or CPF+CPP reversed STZ-induced body weight loss (Figure 1B)
The results indicate that the fragments in CPF with potential anti-diabetic activity were mainly distributed in 90%

Summary

Introduction

Diabetes mellitus is increasing at an alarming rate worldwide, especially in developing countries [1,2]. Type 2 diabetes is characterized by hyperglycemia and insulin deficiency [3,4,5]. Long-term hyperglycemia causes damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels [6]. Hyperglycemiaassociated muscle mass and functional loss appear in the very early stage of diabetes [7]. A recent study showed high blood glucose decelerates WWP1-associated ubiquitous degradation of the transcription factor KLF15, resulting in muscle atrophy [8]. Diabetic nephropathy is a major complication of diabetes; poorly controlled diabetes causes damage to blood vessel clusters in the kidneys, leading to kidney damage and high blood pressure [9]

Objectives

Methods

Results

Conclusion