A Purified Anthraquinone-Glycoside Preparation From Rhubarb Ameliorates Type 2 Diabetes Mellitus by Modulating the Gut Microbiota and Reducing Inflammation.

Hong-Xin Cui,Ling-Shuai Zhang,Ke Yuan,Yang Luo,Zhi-Yong Huang,Ying Guo

doi:10.3389/fmicb.2019.01423

Abstract

Rheum palmatum L. is widely used in traditional Chinese medicine for the treatment of constipation. Here, the therapeutic effects and underlying mechanisms of purified anthraquinone-glycoside preparation from rhubarb (RAGP) on the type 2 diabetes mellitus (T2DM) rats were investigated. After 6 weeks of metformin and RAGP treatment, the weight returned to normal. Fasting blood glucose (FBG), glycated serum protein (GSP), insulin concentration and HOMA-IR index had significantly decreased, and glucagon-like peptide-1 (GLP-1) concentrations had increased. Histological abnormalities in the pancreas and ileum had improved. These effects were associated with enhanced intestinal integrity, thereby reducing the absorption of lipopolysaccharide (LPS) and inflammation. To investigate whether RAGP ameliorated insulin resistance via effects on the gut microbiota, we performed 16s rDNA sequencing of ileal gut contents. This showed an amelioration of gut dysbiosis, with greater abundance of probiotic Lactobacillus and short-chain fatty acid-producing bacteria, and lower abundance of the Lachnospiraceae NK4A136 group and LPS-producing Desulfovibrio. The mechanism of the hypoglycemic effect of RAGP involves regulation of the gut microbiota, activation of the GLP-1/cAMP pathway to ameliorate insulin resistance. Thus, this study provides a theoretical basis for the use of RAGP to treat T2DM, and it may be a novel approach to restore the gut microbiota.

Highlights

Rheum palmatum L., a perennial herb belonging to the Polygonaceae, is well-known in traditional Chinese medicine (TCM) for use in patients with constipation or gastrointestinal hemorrhage and ulcers, and it has antibacterial, anti-inflammatory properties (Zargar et al, 2011)
We used a high-fat, high-sugar diet and low-dose STZ i.p. injection to induce diabetes in rats that mimics the characteristics of human Type 2 diabetes mellitus (T2DM)
The T2DM rats in MET, low dose of purified anthraquinone glycoside preparation from rhubarb (RAGP) (LOW), and high dose of RAGP (HIG) groups slowly regained body mass, and high-dose RAGP treatment had a greater effect (Figure 2A, P < 0.05)

Summary

Introduction

Rheum palmatum L., a perennial herb belonging to the Polygonaceae, is well-known in TCM for use in patients with constipation or gastrointestinal hemorrhage and ulcers, and it has antibacterial, anti-inflammatory properties (Zargar et al, 2011). Rhubarb contains a variety of potentially bioactive components, including anthraquinones, bianthrone, stilbenes, polysaccharides, and tannins. Type 2 diabetes mellitus (T2DM) is widespread worldwide, with an annually escalating incidence. According to statistics from the International Diabetes Federation demonstrate, there were 415 million diabetic patients worldwide in 2015, and this number will increase to 642 million by 2040 (Rocha Fernandes et al, 2016). T2DM involves multiple disorders, including of lipid and glucose metabolism, β-cell dysfunction, chronic low-grade inflammation, and oxidative stress, which result in insulin resistance and insufficient insulin secretion (Tangvarasittichai, 2015; Gutierrez-Rodelo et al, 2017). Rhubarb and other Chinese herbal decoctions have been used to treat diabetes and its complications (Li et al, 2004; Aditya et al, 2015), but anti-diabetic effects of anthraquinoneglycosides have rarely been reported and its mechanism are still unclear

Objectives

Methods

Results

Conclusion