Aqueous extract of Liriope platyphylla, a traditional Chinese medicine, significantly inhibits abdominal fat accumulation and improves glucose regulation in OLETF type II diabetes model rats

Abstract

Liriope platyphylla is a medical herb that has long been used in Korea and China to treat cough, sputum, neurodegenerative disorders, obesity, and diabetes. The aims of this study were to determine the antidiabetic and antiobesity effects of aqueous extract of L. platyphylla (AEtLP) through glucose and lipid regulation in both pre-diabetes and obesity stage of type II diabetes model. Two concentrations of AEtLP were orally administrated to OLETF (Otsuka Long-Evans Tokushima Fatty) rats once a day for 2 weeks, after which changes in glucose metabolism and fat accumulation were measured. Abdominal fat mass dramatically decreased in AEtLP-treated OLETF rats, whereas glucose concentration slightly decreased in all AEtLP-treated rats. However, compared to vehicle-treated OLETF rats, only AEtLP10 (10% concentration)-treated OLETF rats displayed significant induction of insulin production, whereas AEtLP5 (5% concentration)-treated OLETF rats showed a lower level of insulin. Although serum adiponectin level increased in only AEtLP5-treated rats, significant alteration of lipid concentration was detected in AEtLP5-treated OLETF rats. Expression of Glut-1 decreased in all AEtLP-treated rats, whereas Akt phosphorylation increased only in AEtLP10-treated OLETF rats. Furthermore, the pattern of Glut-3 expression was very similar with that of Glut-1 expression, which roughly corresponded with the phosphorylation of c-Jun N-teminal kinase (JNK) and p38 in the mitogen-activated protein kinase pathway. Therefore, these findings suggest that AEtLP should be considered as a therapeutic candidate during pre-diabetes and obesity stage capable of inducing insulin secretion from pancreatic β-cells, glucose uptake in liver cells, as well as a decrease in fat and lipid accumulation.

Keywords: Liriope platyphylla; diabetes; glucose transporter; insulin; signaling pathway.

Figure 1

Effects of AEtLP on body weight and blood glucose and insulin levels. (A) Body weight analysis. At 24 h after final AEtLP treatment, body weight of rats was measured with an electronic balance electronic scale. (B) Glucose and insulin concentration analysis. Blood was collected from abdominal veins of vehicle- and AEtLP-treated OLETF rats. Glucose level was measured using a CareSence Kit, and insulin level was determined using an insulin ELISA kit. (C) Immunohistochemistry. Expression level of insulin was detected in pancreatic islets of vehicle-treated and AEtLP-treated OLETF rats by immunostaining analysis. High intensity was observed in pancreatic islets of AEtLP10-treated OLETF rats as compared with vehicle-treated mice at 200x magnification. Data represent the mean±SD from three replicates. ^*P<0.05 is the significance level compared to LETO rats. ^**P<0.05 is the significance level compared to vehicle-treated group in OLETF rats.

Figure 2

Effects of AEtLP on abdominal fat mass and lipid concentration. (A) At 24 h after final AEtLP treatment, abdominal fat collected from abdominal region of rats and their weight was measured with an electronic balance. Blood was collected from abdominal veins of rats, and (B) adiponectin level in serum was analyzed using an ELISA kit. This kit has 0.1 ng/mL of sensitivity, and the interassay coefficient of variation was between 2.86-5.17. (C-E) Levels of triglycerides, cholesterol, and LDL were analyzed in triplicate using a serum biochemical analyzer. Data represent the mean±SD from three replicates. ^*P<0.05 is the significance level compared to LETO rats. ^**P<0.05 is the significance level compared to vehicle-treated group in OLETF rats.

Figure 3

Glut-1 expression and its regulatory mechanism in liver. Tissue lysates were prepared from liver tissues of LETO, vehicle-, and AEtLP-treated OLETF rats. Fifty micrograms of protein per sample was immunoblotted with antibody for each protein. Glut-1 protein expression was detected with primary antibodies for Glut-1 (A), Akt and p-Akt (B), and horseradish peroxidase-conjugated goat anti-rabbit IgG. Intensity of each protein was calculated using an imaging densitometer. Three out of 4 to 5 rats per group were assayed in duplicate by western blot. Data represent the mean±SD. ^*P<0.05 is the significance level compared to LETO rats. ^**P<0.05 is the significance level compared to vehicle-treated group in OLETF rats.

Figure 4

Glut-3 expression and its regulatory mechanism in the liver. Fifty micrograms of protein per sample was immunoblotted with antibody for p-ERK, ERK, p-JNK, JNK, p38, p-p38, or actin. Intensity of each protein was calculated using an imaging densitometer. Three out of 4 to 5 rats per group were assayed in duplicate by western blot. Data represent the mean±SD. ^*P<0.05 is the significance level compared to LETO rats. ^**P<0.05 is the significance level compared to vehicle-treated group in OLETF rats.