ABSTRACT
This study used an integrated approach to investigate the effects of Gymnema sylvestre (GS) extract as a functional dietary supplement with a high-fat diet. This approach examined insulin resistance, the dysfunction of adipose tissue, and liver steatosis. Male C57BL/6J mice were fed a normal chow or high-fat diet (HFD) for the acute and chronic study, in addition to GS in different doses (100, 250 and 500[Formula: see text]mg/kg body weight). Their body composition changes, serum lipid and glucose parameters, adipose and liver tissue histology, and gene expression were measured. It was found that GS significantly suppressed the increase of body weight, serum levels of lipid, insulin and leptin, and adipose tissue, and liver inflammation. GS also demonstrated hypoglycemic effects due to the amylase inhibition activity. Our results support the existence of a relationship between the HFD induced insulin resistance, adipose dysfunction and liver steatosis. In conclusion, GS works as a functional dietary supplement with preventative effects against metabolic disorder.
Subject(s)
Diet, High-Fat/adverse effects , Dietary Supplements , Gymnema sylvestre , Metabolic Diseases/drug therapy , Metabolic Diseases/prevention & control , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Animals , Blood Glucose/metabolism , Disease Models, Animal , Hypoglycemic Agents , Insulin/metabolism , Insulin Resistance , Leptin/metabolism , Lipids/blood , Male , Metabolic Diseases/etiology , Metabolic Diseases/metabolism , Mice, Inbred C57BLABSTRACT
BACKGROUND: Rab25, a member of Rab family of small guanosine triphosphatase, is associated with progression of various types of human cancers, including lung cancer, the leading cause of cancer-associated deaths around the globe. METHODS: In this study, we report the gene therapeutic effect of short hairpin Rab25 RNA (shRab25) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in female A/J mice. Initially, mice (6 weeks old) were injected with single dose of NNK (2 mg/0.1 mL saline/mouse) by intraperitoneal injection to induce the tumor. Eight weeks later, shRab25 was complexed with glycerol propoxylate triacrylate-spermine (GPT-SPE) copolymer and delivered into tobacco-induced lung cancer models through a nose-only inhalation system twice a week for 2 months. RESULTS: GPT-SPE/shRab25 largely decreased the tobacco-induced tumor numbers and tumor volume in the lungs compared to GPT-SPE- or GPT-SPE/shScr-delivered groups. Remarkably, aerosol-delivered GPT-SPE/shRab25 significantly decreased the expression level of Rab25 and other prominent apoptosis-related proteins in female A/J mice. The apoptosis in these mice was determined by detecting the expression level of Bcl-2, proliferating cell nuclear antigen, Bax, and further confirmed by TUNEL assay. CONCLUSIONS: Our results strongly confirm the tumorigenic role of Rab25 in tobacco carcinogen-induced lung cancer and hence demonstrate aerosol delivery of shRab25 as a therapeutic target for lung cancer treatment.
Subject(s)
Lung Neoplasms/prevention & control , Proteins/genetics , RNA, Small Interfering/administration & dosage , Spermine/administration & dosage , Administration, Inhalation , Aerosols , Animals , Apoptosis/genetics , Carcinogenesis/genetics , Carcinogens/toxicity , Female , Glycerol/chemistry , In Situ Nick-End Labeling , Lung Neoplasms/etiology , Lung Neoplasms/genetics , Mice , Nitrosamines/toxicity , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Small Interfering/genetics , Nicotiana/toxicity , bcl-2-Associated X Protein/geneticsABSTRACT
OBJECTIVE: To investigate the effect of Gymnema sylvestre extract (GS) on initial anti-obesity, liver injury, and glucose homeostasis induced by a high-fat diet (HFD). METHODS: The dry powder of GS was extracted with methanol, and gymnemic acid was identified by high performance liquid chromatography as deacyl gymnemic acid. Male C57BL/6J mice that fed on either a normal diet, normal diet containing 1 g/kg GS (CON+GS), HFD, or HFD containing 1.0 g/kg GS (HFD + GS) for 4 weeks were used to test the initial anti-obesity effect of GS. Body weight gain and food intake, and serum levels about lipid and liver injury markers were measured. Histopathology of adipose tissue and liver stained with hematoxylin and eosin (H&E) and oil-red O were analyzed. After 4 weeks of GS extract feeding, intraperitoneal glucose tolerance test (IPGTT) was performed. RESULTS: The methanol extracts of GS exerted significant anti-obesity effects in HFD + GS group. They decreased body weight gain, a lower food and energy efficiency ratio, and showed lower serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL)-cholesterol, very-low density lipoprotein (VLDL)-cholesterol and leptin compared with the HFD group. The decreases of abdominal as well as epididymal fat weight and adipocyte hypertrophy, lipid droplets in liver, and serum levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) were also observed. The CON + GS group showed an effect of glucose homeostasis compared to the CON group. CONCLUSIONS: This study shows that GS provide the possibility as a key role in an initial anti-obesity effects feeding with a HFD.
