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. 2019 Apr 12;24(8):1454.
doi: 10.3390/molecules24081454.

Ameliorative Effect and Mechanism of the Purified Anthraquinone-Glycoside Preparation from Rheum Palmatum L. on Type 2 Diabetes Mellitus

Fang-Rong Cheng  1 , Hong-Xin Cui  2   3 , Ji-Li Fang  4 , Ke Yuan  5 , Ying Guo  6
Affiliations

Ameliorative Effect and Mechanism of the Purified Anthraquinone-Glycoside Preparation from Rheum Palmatum L. on Type 2 Diabetes Mellitus

Fang-Rong Cheng et al. Molecules. .

Abstract

Rheum palmatum L. is a traditional Chinese medicine with various pharmacological properties, including anti-inflammatory, antibacterial, and detoxification effects. In this study, the mechanism of the hypoglycemic effect of purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR) in streptozotocin (STZ) and high-fat diet induced type 2 diabetes mellitus (T2DM) in rats was investigated. The rats were randomly divided into normal (NC), T2DM, metformin (Met), low, middle (Mid), and high (Hig) does of PAGR groups. After six weeks of continuous administration of PAGR, the serum indices and tissue protein expression were determined, and the pathological changes in liver, kidney, and pancreas tissues were observed. The results showed that compared with the type 2 diabetes mellitus group, the fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) levels in the serum of rats in the PAGR treatment groups were significantly decreased, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels were noticeably increased. The expression of Fas ligand (FasL), cytochrome C (Cyt-c), and caspase-3 in pancreatic tissue was obviously decreased, and the pathological damage to the liver, kidney, and pancreas was improved. These indicate that PAGR can reduce oxidative stress in rats with diabetes mellitus by improving blood lipid metabolism and enhancing their antioxidant capacity, thereby regulating the mitochondrial apoptotic pathway to inhibitβ-cell apoptosis and improve β-cell function. Furthermore, it can regulate Fas/FasL-mediated apoptosis signaling pathway to inhibit β-cell apoptosis, thereby lowering blood glucose levels and improving T2DM.

Keywords: Rheum palmatum L.; apoptosis; oxidative stress; type 2 diabetes mellitus.

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Conflict of interest statement

The authors have no conflicts of interest to declare. All of the authors have approved the final article.

Figures

Figure 1
Figure 1
The structure of the emodin-8-O-β-d-glucoside (I), aloe-emodin-8-O-β-d-glucoside (II), and chrysophanol-8-O-β-d-glucoside (III) and HPLC chromatogram of purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR) (a) and mixed Reference (b).
Figure 2
Figure 2
The changes in body weight (a) and fasting blood glucose (FBG) (b) of rats during the administration of Met and purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR). NC, normal group; T2DM, type 2 diabetes mellitus; Met, metformin group; Low, low group (100 mg/kg); Mid, middle group (200 mg/kg); Hig, high group (400 mg/kg). The data were expressed as mean ± standard deviation (SD) (n = 10), # p < 0.05 ## p < 0.01 vs.NC group; * p < 0.05 ** p < 0.01 vs. T2DM group.
Figure 3
Figure 3
Effects of purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR) on total cholesterol (TC) (a), triglyceride (TG) (b), superoxide dismutase (SOD) (c), glutathione peroxidase (GSH-PX) (d), creatinine (e), and BUN (f) in serum of rats. NC, normal group; T2DM, type 2 diabetes mellitus; Met, metformin group; Low, low group (100 mg/kg); Mid, middle group (200 mg/kg); Hig, high group (400 mg/kg). The data were expressed as mean ± SD (n = 10), # p < 0.05, ## p < 0.01 vs. NC group. * p < 0.05, ** p < 0.01 vs. T2DM group.
Figure 4
Figure 4
The effects of purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR) on histopathological changes in the liver of rats. Histological observation, H&E, a–f×200; (a), normal (NC) group; (b), type 2 diabetes mellitus (T2DM) group; (c), metformin (Met) group; (d), Low group; (e), middle (Mid) group; (f), high (Hig) group; CV, central veins; formula image, hepatocyte; formula image, inflammatory cell; formula image, lipid droplet.
Figure 5
Figure 5
Effects of purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR) on histopathological changes in the kidney of rats. Histological observation, H&E, a-f×400; (a), normal (NC) group; (b), type 2 diabetes mellitus (T2DM) group; (c), metformin (Met) group; (d), Low group; (e), middle (Mid) group; (f), high (Hig) group; formula image, glomerulus; formula image, base membrane; formula image, mesangial.
Figure 6
Figure 6
Effects of purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR) on histopathological changes in the pancreas of rats. Histological observation, H&E, a–f×400; (a), normal (NC) group; (b), type 2 diabetes mellitus (T2DM) group; (c), metformin (Met) group; (d), Low group; (e), middle (Mid) group; (f), high (Hig) group; formula image, islet; formula image, islet cell; formula image, lipid droplet.
Figure 7
Figure 7
The effect of purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR) on the protein expression of Fas ligand (FasL), cytochrome C (Cyt-c), and Caspase-3 in pancreatic tissue. NC, normal group; T2DM, type 2 diabetes mellitus; Met, metformin group; Low, low group (100 mg/kg); Mid, middle group (200 mg/kg); Hig, high group (400 mg/kg).
Figure 8
Figure 8
The signaling pathway of apoptosis. Hyperglycemia leads to the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) which change the membrane potential of mitochondria, leading to the release of cytochrome C (Cyt-c). It also leads to the expression of Fas ligand (FasL) and Fas, and they combine to form the Fas-associated death domain protein (FADD). The Cyt-c and FADD all activate caspase cascade reaction, leading to apoptosis.
See this image and copyright information in PMC

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