Hepatic protection by glycyrrhizin and inhibition of iNOS expression in concanavalin A-induced liver injury in mice
ABSTRACT In this study, the possible protective effect of glycyrrhizin (GL), an active compound derived from licorice root, was examined on T cell-mediated liver injury in mice.
Mice were subjected to liver injury by intravenous injection of concanavalin A (Con A). They had been treated with GL (i.p.) 30 min before the injection. Liver injury was estimated by measuring serum levels of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST), and by examining liver sections with hematoxylin-eosin staining. Expression of inducible nitric oxide synthase (iNOS) mRNA and protein in the liver was determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting.
Serum transaminases and hepatic iNOS levels increased with time after Con A treatment. Expression of iNOS mRNA in the liver was elevated for up to 8 h, and at 8 h, GL (ED(50): 10.5 mg/kg) suppressed the increases in AST and ALT in response to Con A. An increase in iNOS mRNA expression and protein was inhibited by treatment with GL. Furthermore, GL inhibited cell infiltration and the degeneration of hepatocytes in the liver of Con A-treated mice.
The present study suggests that the prevention by GL of Con A-induced hepatitis is due partly to the modulation of hepatic iNOS induction and of degeneration of hepatocytes.
- SourceAvailable from: Alessandro Federico
[Show abstract] [Hide abstract]
- "In animal studies, GL inhibits CD4+ T-cell and tumor necrosis factor- (TNF-) mediated cytotoxicity , activated NK cells and extrathymic T lymphocyte differentiation [94, 95], and promoted maturation of dendritic cells . "
ABSTRACT: Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice. We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin. We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role) in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology). The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population.Evidence-based Complementary and Alternative Medicine 09/2012; 2012(9):837939. DOI:10.1155/2012/837939 · 1.88 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Glycyrrhizin (GL), a major active constituent of licorice root, has been attributed numerous pharmacologic effects, including anti-inflammatory, anti-viral, anti-tumor, and hepatoprotective activities. In this study, we investigated the anti-inflammatory effect of GL on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in Balb/c mice by intratracheal instillation of LPS (1 mg/kg). Before 1 h of LPS administration, the mice received intraperitoneal injection of GL at varied doses (10, 25, and 50 mg/kg). The severity of pulmonary injury was evaluated 12 h after LPS administration. GL pretreatment led to significant attenuation of LPS induced evident lung histopathologic changes, alveolar hemorrhage, and neutrophil infiltration with evidence of reduced myeloperoxidase (MPO) activity. The lung wet/dry weight ratios, as an index of lung edema, were markedly reduced by GL pretreatment. The concentrations of pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α were elevated in bronchoalveolar lavage fluid (BALF) after LPS administration, which were significantly inhibited by GL pretreatment. GL pretreatment also reduced the concentrations of nitric oxide (NO) in lung tissues. Furthermore, the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was suppressed by GL pretreatment. In conclusion, GL potently protected against LPS-induced ALI, and the protective effects of GL may attribute partly to the suppression of COX-2 and iNOS expression.Journal of Surgical Research 11/2010; 165(1):e29-35. DOI:10.1016/j.jss.2010.10.004 · 1.94 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Licorice has been used in Chinese folk medicine for the treatment of various disorders. Licorice has the biological capabilities of detoxication, antioxidation, and antiinfection. In this study, we evaluated the antihepatotoxic effect of licorice aqueous extract (LE) on the carbon tetrachloride (CCl(4))-induced liver injury in a rat model. Hepatic damage, as reveled by histology and the increased activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, and decreased levels of serum total protein (TP), albumin (Alb) and globulin (G) were induced in rats by an administration of CCl(4) at 3 mL/kg b.w. (1:1 in groundnut oil). Licorice extract significantly inhibited the elevated AST, ALP and ALT activities and the decreased TP, Alb and G levels caused by CCl(4) intoxication. It also enhanced liver super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), Glutathione S-transferase (GST) activities and glutathione (GSH) level, reduced malondialdehyde (MDA) level. Licorice extract still markedly reverses the increased liver hydroxyproline and serum TNF-α levels induced by CCl(4) intoxication. The data of this study support a chemopreventive potential of licorice extract against liver oxidative injury.International Journal of Molecular Sciences 12/2011; 12(10):6529-43. DOI:10.3390/ijms12106529 · 2.86 Impact Factor