ABSTRACT
This study evaluated the antilipogenic and anti-inflammatory effects of Codonopsis lanceolata (C. lanceolata) root extract in mice with alcohol-induced fatty liver and elucidated its underlying molecular mechanisms. Ethanol was introduced into the liquid diet by mixing it with distilled water at 5% (wt/v), providing 36% of the energy, for nine weeks. Among the three different fractions prepared from the C. lanceolata root, the C. lanceolata methanol extract (CME) exhibited the most remarkable attenuation of alcohol-induced fatty liver with respect to various parameters such as hepatic free fatty acid concentration, body weight loss, and hepatic accumulations of triglyceride and cholesterol. The hepatic gene and protein expression levels were analysed via RT-PCR and Western blotting, respectively. CME feeding significantly restored the ethanol-induced downregulation of the adiponectin receptor (adipoR) 1 and of adipoR2, along with their downstream molecules. Furthermore, the study data showed that CME feeding dramatically reversed ethanol-induced hepatic upregulation of toll-like receptor- (TLR-) mediated signaling cascade molecules. These results indicate that the beneficial effects of CME against alcoholic fatty livers of mice appear to be with adenosine- and adiponectin-mediated regulation of hepatic steatosis and TLR-mediated modulation of hepatic proinflammatory responses.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Codonopsis/chemistry , Fatty Liver, Alcoholic/prevention & control , Lipid Regulating Agents/administration & dosage , Plant Extracts/administration & dosage , Adenosine/genetics , Adenosine/metabolism , Animals , Cholesterol/metabolism , Disease Models, Animal , Ethanol/toxicity , Gene Expression Regulation/drug effects , Liver/drug effects , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Adiponectin/genetics , Receptors, Adiponectin/metabolism , Signal Transduction/drug effects , Toll-Like Receptors/genetics , Toll-Like Receptors/metabolism , Triglycerides/metabolismABSTRACT
The fruit of Terminalia chebula Retz. (T. chebula), which is a member of the Combfreetaceae family, is used widely in Asian countries as a traditional folk medicine, and its extract has been reported to be an anticancer, antidiabetic and anticaries agent. In our previous study, chebulic acid isolated from T. chebula extract was confirmed to show antioxidant activity and protective action against endothelial cell dysfunction. In order to support the safety-in-use of the ethyl acetate (EtOAc)-soluble portion of a T. chebula ethanol extract containing 29.4% chebulic acid content, the prepared portion was tested in an in vitro mutagenicity assay, and a single- and 14-day repeated dose oral toxicity study. In the bacterial mutation assay, up to 5000 µg/mL concentration of the EtOAc-soluble portion, the numbers of colonies did not increase whether with or without metabolic activation. In the oral toxicity study, the single oral dose of the extract at 2000 mg/kg did not produce mortality or abnormal lesions in the internal organs of rats. The results of a 14-day orally repeated dose showed that the EtOAc-soluble portion of T. chebula ethanol extracts gave no adverse effects at dosages of 2000 mg/kg in rats in the study.
Subject(s)
Benzopyrans/adverse effects , Mutagenesis , Plant Extracts/toxicity , Terminalia/toxicity , Animals , Bacteria/drug effects , Bacteria/genetics , Colony Count, Microbial , Death , Female , Fruit , Male , Mutagenicity Tests , Mutagens/toxicity , Rats , Rats, Sprague-Dawley , Terminalia/chemistryABSTRACT
Terminalia chebula has been widely used in India as a folk medicine. This study investigated the in vivo anti-hyperglycemia and anti-diabetic complication effects of the EtOAc-soluble portion of ethanolic extract of T. chebula fruit (EETC) containing 29.4% chebulic acid. Rats were divided into non-diabetic, untreated diabetic and diabetic groups. Streptozotocin (40 mg/kg body weight (BW))-induced diabetic rats were orally administered the aminoguanidine (100 mg/kg BW), high dose (500 mg/kg BW; HEETC) and low dose (100 mg/kg BW; LEETC) for 13 weeks. HEETC administration reduced the levels of blood glucose and serum lipids, decreased malondialdehyde concentrations of serum and thoracic aorta in diabetic rats, and significantly improved serum biochemical values and the pathomorphological changes of the liver and kidney in diabetic rats. Also, HEETC decreased the advanced glycation end products (AGEs) distribution in testis seminiferous tubules. Therefore, HEETC has a merit to be a potent candidate to control glycemic and diabetic complications.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/therapeutic use , Phytotherapy , Plant Extracts/therapeutic use , Terminalia/chemistry , Administration, Oral , Animals , Aorta, Thoracic/metabolism , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Fruit , Glycation End Products, Advanced/metabolism , Hypoglycemic Agents/pharmacology , Kidney/drug effects , Kidney/pathology , Kidney Diseases/etiology , Kidney Diseases/pathology , Kidney Diseases/prevention & control , Lipids/blood , Liver/drug effects , Liver/pathology , Liver Diseases/etiology , Liver Diseases/pathology , Liver Diseases/prevention & control , Male , Malondialdehyde/blood , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley , Seminiferous Tubules/metabolism , SolubilityABSTRACT
Plantago asiatica is a member of the Plantaginaceae family, and is widely distributed in East Asia. In our previous work, a single active compound, plantamajoside was isolated and confirmed to have glycation inhibitory activity, and did not possess toxicity during a 90 day repeated oral toxicity test in rats. In the present study, a chromosomal aberration test was performed to investigate the genotoxicity of plantamajoside. From the results of the cytotoxicity test, plantamajoside proved to be less toxic when it was treated combined with S9 cell fractions. However, there was a significant increase in structural aberrations during the short-term treatment of plantamajoside at its highest dose (5000 microg/mL) even when combined with S9. This seems to have been a natural phenomenon due to the very high dose of plantamajoside that was used. However, to confirm the safety of plantamajoside for its potential use as a phytochemical agent in health products, additional mutagenicity tests are necessary.