Abstract:Abstract. High mobility group box-1 protein (HMGB1), primarily from the nucleus, is released into the extracellular milieu either passively from necrotic cells or actively through secretion by monocytes/macrophages. Extracellular HMGB1 acts as a potent inflammatory agent by promoting the release of cytokines such as tumor necrosis factor (TNF)-·, has procoagulant activity, and is involved in death due to sepsis. Accordingly, HMGB1 is an appropriate therapeutic target. In this study, we found that an extract of… Show more
“…These findings suggest that HMGB1 is a potential target for the treatment of hepatic IRI. OA inhibits HMGB1-mediated pathway activation in lipopolysaccharide-stimulated RAW264.7 cells [32] and human umbilical vein endothelial cells [33]. HMGB1 acts as a late mediator of the inflammatory response, activating monocytes to secrete proinflammatory cytokines, including TNF- α and IL-1 [34], and inducing inflammation as the ligand of TLR4 [18].…”
Hepatic ischemia reperfusion (IR) injury (IRI) occurs during liver transplantation, hepatectomy, and hemorrhagic shock. Oleanolic acid (OA) is a natural compound with antioxidant and anti-inflammatory activity that has been used to treat liver disorders in clinical practice for several years. Here, we investigated the effects and underlying mechanisms of OA in hepatic IRI. A 60-minute partial (70%) hepatic, warm, ischemic reperfusion model was established in BALB/c mice, and two doses (30 and 60 mg/kg) of OA were administered intragastrically for 7 consecutive days prior to hepatic IR. Orbital blood and liver specimens were collected at 2, 8, and 24 h after IR. The results showed that OA preconditioning significantly alleviated hepatic injury, as evidenced by decreased alanine aminotransferase and aspartate aminotransferase levels; improved histology, inhibition of JNK phosphorylation, and high mobility group box 1 (HMGB1); and tumor necrosis factor-α downregulation in hepatic IR mice. OA upregulated Bcl-2 and downregulated caspase-3, caspase-9, Bax, Beclin 1, and LC3, which play crucial roles in the regulation of apoptosis and autophagy. These findings highlighted the protective effects of OA against hepatic IRI mediated by the inhibition of apoptosis and autophagy and the release of HMGB1, which acted as a late inflammatory mediator in hepatic IRI.
“…These findings suggest that HMGB1 is a potential target for the treatment of hepatic IRI. OA inhibits HMGB1-mediated pathway activation in lipopolysaccharide-stimulated RAW264.7 cells [32] and human umbilical vein endothelial cells [33]. HMGB1 acts as a late mediator of the inflammatory response, activating monocytes to secrete proinflammatory cytokines, including TNF- α and IL-1 [34], and inducing inflammation as the ligand of TLR4 [18].…”
Hepatic ischemia reperfusion (IR) injury (IRI) occurs during liver transplantation, hepatectomy, and hemorrhagic shock. Oleanolic acid (OA) is a natural compound with antioxidant and anti-inflammatory activity that has been used to treat liver disorders in clinical practice for several years. Here, we investigated the effects and underlying mechanisms of OA in hepatic IRI. A 60-minute partial (70%) hepatic, warm, ischemic reperfusion model was established in BALB/c mice, and two doses (30 and 60 mg/kg) of OA were administered intragastrically for 7 consecutive days prior to hepatic IR. Orbital blood and liver specimens were collected at 2, 8, and 24 h after IR. The results showed that OA preconditioning significantly alleviated hepatic injury, as evidenced by decreased alanine aminotransferase and aspartate aminotransferase levels; improved histology, inhibition of JNK phosphorylation, and high mobility group box 1 (HMGB1); and tumor necrosis factor-α downregulation in hepatic IR mice. OA upregulated Bcl-2 and downregulated caspase-3, caspase-9, Bax, Beclin 1, and LC3, which play crucial roles in the regulation of apoptosis and autophagy. These findings highlighted the protective effects of OA against hepatic IRI mediated by the inhibition of apoptosis and autophagy and the release of HMGB1, which acted as a late inflammatory mediator in hepatic IRI.
“…Extracellular high-mobility group box-1 protein (HMGB1) is a potent inflammatory agent that can promote the release of pro-inflammatory mediators such as TNF-α. The triterpenoid compounds extracted from P. mume, such as oleanolic acid (compound 133), inhibited HMGB1 release from lipopolysaccharide (LPS)-stimulated RAW246.7 cells via the Nrf2/HO-1 pathway (Kawahara et al, 2009). MK615 or a water extract of P. mume inhibited the production of cytokines induced by LPS in RAW246.7 cells and in gingival fibroblast cells.…”
Section: Anti-inflammatory and Antioxidant Activitiesmentioning
Prunus mume is one of the most ancient medicinal herbs and health foods commonly used in Asian countries. It is widely used as a constituent of many medicinal preparations and as a food ingredient for its beneficial health effects. In this review, we retrieved reports from PubMed, embase, Scopus, and SciFinder databases, to collect extensive scientific evidence on the phytochemical constituents, pharmacological properties, and clinical applications of Prunus mume. The literature review revealed that approximately 192 compounds have been isolated from different parts of the plant, and their molecular structures have been identified. The pharmacological properties of the plant, including anti-diabetic, liver-protective, antitumor, antimicrobial, antioxidant, and anti-inflammatory activities, as well as their underlying mechanisms, have been clarified by in vitro and in vivo studies. Clinical studies, although very limited, have been highlighted in this review to provide a reference for further exploration on therapeutic applications of the plant.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.