Abstract:Diammonium Glycyrrhizinate could reduce inflammatory injury in a rat model of ulcerative colitis. This may occur via suppression of NF-kappaB, TNF-alpha and ICAM-1 in colonic mucosa.
“…It was also reported that GA scavenges free radical species by increasing superoxide dismutase activity in atherosclerotic and hypercholesterolemic rabbits [15] . More recently, studies have suggested that GA and its derivatives may abolish TNF-α-induced leukocyte adhesion and extravasation in the in vivo microcirculation, and attenuate the elevation of ICAM-1 expression in rat models of hepatic injury and colic ulceration [16][17][18] . However, the effect of GA on ICAM-1 expression in cytokine-activated vascular endothelial cells is not clearly defined.…”
Aim: To investigate the effects of glycyrrhetinic acid (GA), an active component extracted from the root of Glycyrrhizae glabra, on the expression of intercellular adhesion molecule-1 (ICAM-1) in tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelial cells (HUVEC). Methods: ICAM-1 mRNA and protein levels were detected using RT-PCR and cell enzyme-linked immunosorbent assays. The adherence of human monocytic THP-1 cells labeled with [ 3 H]thymidine to HUVEC was determined by counting radioactivity with a scintillation counter. The activation of mitogen-activated protein kinases as well as the degradation of IκB and nuclear factor-κB (NF-κB) or phospho-cJun in the nucleus were detected by western blots. NF-κB binding activity was detected using electrophoretic mobility shift assay. Results:GA (50 and 100 mmol/L) significantly inhibits TNF-α-induced ICAM-1 mRNA and protein expressions, as well as THP-1 cell adhesiveness in HUVEC. GA selectively inhibited TNF-α-activated signal pathway of c-Jun N-terminal kinase (JNK), without affecting extracellular signal-regulated kinase 1/2 and p38. Furthermore, GA apparently inhibited IκB/NF-κB signaling system by preventing IκB degradation, NF-κB translocation, and NF-κB/DNA binding activity. Finally, pretreatment with GA or the inhibitors of NF-κB, JNK, and p38 reduced the ICAM-1 protein expression induced by TNF-α. Conclusion: GA inhibits TNF-α-stimulated ICAM-1 expression, leading to a decrease in adherent monocytes to HUVEC. This inhibition is attributed to GA interruption of both JNK/c-Jun and IκB/NF-κB signaling pathways, which decrease activator protein-1 (AP-1) and NF-κB mediated ICAM-1 expressions. The results suggest that GA may provide a beneficial effect in treating vascular diseases associated with inflammation, such as atherosclerosis.
“…It was also reported that GA scavenges free radical species by increasing superoxide dismutase activity in atherosclerotic and hypercholesterolemic rabbits [15] . More recently, studies have suggested that GA and its derivatives may abolish TNF-α-induced leukocyte adhesion and extravasation in the in vivo microcirculation, and attenuate the elevation of ICAM-1 expression in rat models of hepatic injury and colic ulceration [16][17][18] . However, the effect of GA on ICAM-1 expression in cytokine-activated vascular endothelial cells is not clearly defined.…”
Aim: To investigate the effects of glycyrrhetinic acid (GA), an active component extracted from the root of Glycyrrhizae glabra, on the expression of intercellular adhesion molecule-1 (ICAM-1) in tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelial cells (HUVEC). Methods: ICAM-1 mRNA and protein levels were detected using RT-PCR and cell enzyme-linked immunosorbent assays. The adherence of human monocytic THP-1 cells labeled with [ 3 H]thymidine to HUVEC was determined by counting radioactivity with a scintillation counter. The activation of mitogen-activated protein kinases as well as the degradation of IκB and nuclear factor-κB (NF-κB) or phospho-cJun in the nucleus were detected by western blots. NF-κB binding activity was detected using electrophoretic mobility shift assay. Results:GA (50 and 100 mmol/L) significantly inhibits TNF-α-induced ICAM-1 mRNA and protein expressions, as well as THP-1 cell adhesiveness in HUVEC. GA selectively inhibited TNF-α-activated signal pathway of c-Jun N-terminal kinase (JNK), without affecting extracellular signal-regulated kinase 1/2 and p38. Furthermore, GA apparently inhibited IκB/NF-κB signaling system by preventing IκB degradation, NF-κB translocation, and NF-κB/DNA binding activity. Finally, pretreatment with GA or the inhibitors of NF-κB, JNK, and p38 reduced the ICAM-1 protein expression induced by TNF-α. Conclusion: GA inhibits TNF-α-stimulated ICAM-1 expression, leading to a decrease in adherent monocytes to HUVEC. This inhibition is attributed to GA interruption of both JNK/c-Jun and IκB/NF-κB signaling pathways, which decrease activator protein-1 (AP-1) and NF-κB mediated ICAM-1 expressions. The results suggest that GA may provide a beneficial effect in treating vascular diseases associated with inflammation, such as atherosclerosis.
“…DG possesses a high antiinflammatory effect, which protects the hepatic cell membrane, and ameliorates liver function (Xu et al 2009;Yuan et al 2006). It would undoubtedly be beneficial to understand the mechanisms of the hepatoprotective effect of this herbal ingredient in metabolic regulation.…”
“…Clinically, DG is widely used in the therapy of chronic hepatitis for its effects of inhibiting inflammatory reactions and ischemia-reperfusion injury. These effects have been demonstrated to be beneficial in rat models of ulcerative colitis and cerebral ischemia reperfusion (7,8). The present study focused on its effect on random skin flap survival in rats.…”
Section: Discussionmentioning
confidence: 99%
“…Currently, DG is widely administered to patients with chronic hepatitis and human immunodeficiency virus infection for its anti-inflammatory, anti-viral and hepatoprotective effects (5,6). A previous study in a model of ulcerative colitis indicated that DG was able to reduce inflammatory injury via suppression of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α and intercellular adhesion molecule 1, which are thought to promote inflammatory injury (7). Furthermore, it was found that DG had neuroprotective potential against ischemia-reperfusion injury in a model of focal cerebral ischemic-reperfusion injury, and this effect was also likely associated with the anti-inflammatory function of DG according to a previous study (8).…”
Abstract. Partial necrosis of skin flaps continues to restrict the survival of local skin flaps following plastic and reconstructive surgeries. The aim of the present study was to investigate the effects of diammonium glycyrrhizinate (DG), a salt of glycyrrhetinic acid that has been widely used in the therapy of chronic hepatitis and human immunodeficiency virus infection, on random skin flap survival in rats. McFarlane flaps were established in 60 male Sprague-Dawley rats randomly divided into three groups. Group I served as the control group and was injected with saline (10 mg/kg) once per day. Group II and group III were the experimental groups, and were injected with 10 mg/kg DG once and twice per day, respectively. On day 7, the survival area of the flap was measured. Tissue samples were stained with hematoxylin and eosin and immunohistochemically evaluated. Tissue edema, neutrophil density, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were evaluated. The mean survival areas of the flaps of group II were significantly larger when compared with those of group I (P<0.05), and the rats of group III exhibited significantly higher survival areas than group II (P<0.05). Histologic and immunohistochemical evaluation showed that microvessel development and the expression level of vascular endothelial growth factor were higher in the two experimental groups than in the control group. Furthermore, SOD activity was significantly increased (P<0.05), while the neutrophil density and MDA level were significantly reduced (P<0.05) in group II when compared with group I. Significant differences between group II and group III with regard to SOD activity and MDA level were also observed (P<0.05). Thus, DG may have a dose-dependent effect on promoting the survival of random skin flaps.
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