ABSTRACT
Control of inflammation is widely accepted as an important strategy for cancer chemoprevention. Anti-inflammatory effects of bark extracts of elm tree (BEE) have been amply reported. Therefore, BEE may be a good candidate cancer chemopreventive agent. Considering the high incidence of hepatic cancer and limited therapeutic approaches for treating this disease, it is important to develop liver cancer-specific chemopreventive agents. To evaluate the chemopreventive potential of BEE, we investigated the growth inhibition effect of BEE on the HepG2 human hepatocellular carcinoma cell line. We performed a cell counting kit-8 assay to determine cell viability, and 4,6-diamino-2-phenylindole staining and flow cytometry to measure apoptotic cell death. Finally, the expression levels of pro- and anti-apoptotic proteins were measured. BEE inhibited the growth of HepG2 cells and induced apoptosis in a dose-dependent manner. Pro-apoptotic activity was promoted via the mitochondrial pathway of apoptosis, as demonstrated by the activation of pro-apoptotic proteins Bax, caspase-9, caspase-3, and poly (ADP-ribose) polymerase as well as the down-regulation of the anti-apoptotic protein Bcl-2. These results suggest that BEE may have potential use in hepatic cancer chemoprevention by suppressing cancer cell growth via pro-apoptotic activity.
Subject(s)
Humans , Apoptosis/drug effects , Blotting, Western , Carcinoma, Hepatocellular/drug therapy , Caspase 3/metabolism , Caspase 9/metabolism , Cell Survival/drug effects , Flow Cytometry , Hep G2 Cells , Indoles/chemistry , Liver Neoplasms/drug therapy , Plant Bark/chemistry , Plant Extracts/pharmacology , Poly(ADP-ribose) Polymerases/metabolism , Ulmus/chemistry , bcl-2-Associated X Protein/metabolismABSTRACT
Ulmus davidiana var. japonica Rehder (Urticales: Ulmaceae) (UD) is a tree widespread in northeast Asia. It is traditionally used for anticancer and anti-inflammatory therapy. The present study investigated the effect of an ethanol extract of UD on vascular tension and its underlying mechanism in rats. The dried root bark of UD was ground and extracted with 80% ethanol. The prepared UD extract was used in further analysis. The effect of UD on the cell viability, vasoreactivity and hemodynamics were investigated using propidium iodide staining in cultured cells, isometric tension recording and blood pressure analysis, respectively. Low dose of UD (10~100microg/ml) did not affect endothelial cell viability, but high dose of UD reduced cell viability. UD induced vasorelaxation in the range of 0.1~10microg/ml with an ED50 value of 2microg/ml. UD-induced vasorelaxation was completely abolished by removal of the endothelium or by pre-treatment with L-NAME, an inhibitor of nitric oxide synthase. UD inhibited calcium influx induced by phenylephrine and high K+ and also completely abolished the effect of L-NAME. Intravenous injection of UD extracts (10~100 mg/kg) decreased arterial and ventricular pressure in a dose-dependent manner. Moreover, UD extracts reduced the ventricular contractility (+dP/dt) in anesthetized rats. However, UD-induced hypotensive actions were minimized in L-NAME-treated rats. Taken together, out results showed that UD induced vasorelaxation and has antihypertensive properties, which may be due the activation of nitric oxide synthase in endothelium.
Subject(s)
Animals , Rats , Asia , Blood Pressure , Calcium , Cell Survival , Cells, Cultured , Endothelial Cells , Endothelium , Ethanol , Hemodynamics , Injections, Intravenous , NG-Nitroarginine Methyl Ester , Nitric Oxide Synthase , Nitric Oxide Synthase Type III , Phenylephrine , Propidium , Trees , Ulmus , Vasodilation , Ventricular PressureABSTRACT
This study was conducted to investigate the effects of Aralia elata, Acanthopanacis cortex and Ulmus davidiana water extracts on blood hemoglobin, HbA1c levels and biomarkers in the streptozotocin (STZ)-induced diabetic rats. Male Wistar rats divided into normal and diabetic groups. The diabetic groups subdivided into the control group (DM) and Araliaceae water extracts supplemented groups: Aralia elata (AE), Acanthopanacis cortex (AC) and Ulmus davidiana (UD). The extracts were supplemented in diet base on 11.42 g of raw Araliaceae/kg diet for 7 weeks. The diabetes was induced by injecting STZ (55 mg/kg B.W., i.p.) once 2 weeks before sacrifying. Relative weights of liver were significantly lowered in the DM group compared to the normal group, whereas those of kidney and heart were significantly increased in the DM group. Supplementation of the Araliaceae water extracts improved reduced liver weights in STZ-induced diabetic rats. Blood glucose level was significantly higher in the DM group than in the normal group, whereas insulin contents were significantly lowered in the DM groups. However, these parameters were normalized in the AE, AC and UD supplemented groups, respectively. Blood hemoglobin and HbA(1c) levels were significantly higher in the DM group than in the normal group. When all of Araliaceae water extracts were supplemented to the diabetic rats lowered hemoglobin and HbAI(1c) levels. Red blood cell, white blood cell and lymphocyte were significantly higher in the DM group than in the normal group. The supplementation of Araliaceae family water extracts significantly lowered these parameters compared to the DM group. MCV, MCH contents were declined in the DM group, while the supplementation of Aralia elata, Acanthopanacis cortex and Ulmus davidiana water extracts elevated of these contents in STZ-induced diabetic rats. Accordingly, these results indicate that Aralia elata, Acanthopanacis cortex and Ulmus davidiana water extracts would seem to improve the blood biomarkers in STZ-induced diabetic rats.