Hepatoprotective effects of salidroside on fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide in mice.
ABSTRACT The aim was to investigate the protective effect of salidroside isolated from Rhodiola sachalinensis A. Bor. (Crassulaceae) on D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure.
Hepatotoxicity was induced by an intraperitoneal injection of D-galactosamine (700 mg/kg) and lipopolysaccharide (10 mug/kg); salidroside (20, 50 and 100 mg/kg) was administered intraperitoneally 1 h before induction of hepatoxicity. Liver injury was assessed biochemically and histologically.
Salidroside attenuated the induced acute increase in serum aspartate aminotransferase and alanine aminotransferase activities, and levels of tumour necrosis factor-alpha levels and serum nitric oxide. It restored depleted hepatic glutathione, superoxide dismutase, catalase and glutathione peroxidase activities, decreased malondialdehyde levels and considerably reduced histopathological changes. Histopathological, immunohistochemical and Western blot analyses also demonstrated that salidroside could reduce the appearance of necrotic regions and expression of caspase-3 and hypoxia-inducible factor-1alpha in liver tissue.
Salidroside protected liver tissue from the oxidative stress elicited by D-galactosamine and lipopolysaccharide. The hepatoprotective mechanism of salidroside appear to be related to antioxidant activity and inhibition of hypoxia-inducible factor-1alpha.
Article: Highest Frequencies of Interleukin-22-Producing T Helper Cells in Alcoholic Hepatitis Patients with a Favourable Short-Term Course.[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Alcoholic hepatitis (AH) has a severe prognosis due to hepatic inflammatory injury. The cytokine interleukin-22 (IL-22) is reported to exert anti-apoptotic and proliferative effects, but IL-22 has not been studied during the course of AH. IL-22 is mainly produced by CD4(+) (helper) T cells, including Th17 cells. In addition, Th17 cells produce the proinflammatory cytokine IL-17A, which has been implicated in AH. AIMS: We aimed to study the levels of circulating IL-22- and IL-17A-producing T helper cells and plasma cytokines in patients with AH and to examine the observations in relation to the short-term disease course. METHODS: We collected blood samples from 21 consecutive patients with severe AH on days 0, 14 and 30 after diagnosis, and included 10 stable alcoholic cirrhosis patients and 10 healthy subjects as controls. Analyses were performed using flow cytometry and ELISA. RESULTS: We found higher frequencies of IL-22-producing T helper cells in AH patients (median 1.7%) than in cirrhosis patients (1.0%, p = 0.03) and healthy controls (1.0%, p = 0.01), and a 1.5-fold increase in the plasma concentration of IL-17A in AH compared with healthy controls (p<0.01). Those patients who markedly improved their Glasgow Alcoholic Hepatitis Score demonstrated a 2-fold higher frequency of IL-22-producing T helper cells at baseline and during follow-up than patients whose condition deteriorated (p = 0.04). CONCLUSIONS: The frequency of IL-22-producing T helper cells was increased in AH patients and most so in those whose condition seemed to improve. T cell differentiation toward an IL-22-producing phenotype may thus be favourable in AH.PLoS ONE 01/2013; 8(1):e55101. · 4.09 Impact Factor
Article: Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study.[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far. METHODS: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications. RESULTS: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P <0.001). Elevated levels of IL-22 were associated with ascites (P = 0.006), hepatorenal syndrome (P <0.0001), and spontaneous bacterial peritonitis (P = 0.001). Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). CONCLUSIONS: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis.BMC Medicine 09/2012; 10(1):102. · 6.03 Impact Factor
Article: Protective effect of salidroside from Rhodiolae Radix on diabetes-induced oxidative stress in mice.[show abstract] [hide abstract]
ABSTRACT: It has been confirmed that diabetes mellitus (DM) carries increased oxidative stress. This study evaluated the effects of salidroside from Rhodiolae Radix on diabetes-induced oxidative stress in mice. After induction of diabetes, diabetic mice were administered daily doses of 50, 100 and 200 mg/kg salidroside for 28 days. Body weights, fasting blood glucose (FBG), serum insulin, TC (total cholesterol), TG (triglyceride), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured. Results showed that salidroside possessed hypoglycemic activity and protective effects against diabetes-induced oxidative stress, which could significantly reduce FBG, TC, TG and MDA levels, and at same time increase serum insulin levels, SOD, GPx and CAT activities. Therefore, salidroside should be considered as a candidate for future studies on diabetes.Molecules 01/2011; 16(12):9912-24. · 2.39 Impact Factor