shikonin and Acute-Lung-Injury

Shikonin is the major active component in

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Bronchoalveolar Lavage Fluid; Caspase 3; Cytokines; Disease Models, Animal; DNA Fragmentation; Inflammation; Lipopolysaccharides; Male; Mice, Inbred C57BL; Myeloid Cell Leukemia Sequence 1 Protein; Naphthoquinones; Neutrophil Infiltration; Neutrophils; Poly(ADP-ribose) Polymerases; Teichoic Acids; Tumor Suppressor Protein p53

Shikonin is an anti-inflammatory agent extracted from natural herbs. The aim of this study is to explain the treatment effects and mechanism of Shikonin in acute lung injury induced by sepsis. In this study, first, we evaluate different Shikonin concentrations for the anti-inflammation of acute lung injury induced by sepsis in an in vivo study. On the basis of the results, we confirm that 50.0 mg/kg was the best therapeutic Shikonin concentration. As a second step, we discuss the mechanism of Shikonin by a vitro cell experiment. Finaly, we validate that Shikonin has effective treatment effects on acute lung injury via regulation of microRNA-140-5p/toll-like receptor 4 (miRNA-140-5p/TLR4) in the in vivo study. The results of vitro and vivo study showed that Shikonin could improve acute lung injury induced by sepsis. The mechanism might be correlation miRNA-140-5p expression increasing, and regulated targeted gene TLR4, with TLR4 expression depressing, the downstream myeloid differentiation protein 88 and nuclear factor κB proteins expression were suppressed. In conclusion, Shikonin improved sepsis induced lung injury by regulation miRNA-140-5p/TLR4.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Cell Proliferation; Cells, Cultured; Gene Expression Regulation; Male; MicroRNAs; Naphthoquinones; Rats; Sepsis; Specific Pathogen-Free Organisms; Toll-Like Receptor 4

Acute lung injury (ALI) is a challenging clinical syndrome, which manifests as an acute inflammatory response. Myeloid differentiation protein 2 (MD2) has an important role in mediating LPS-induced inflammation. Currently, there are no effective molecular-based therapies for ALI or viable biomarkers for predicting the severity of disease. Recent preclinical studies have shown that shikonin, a natural naphthoquinone, prevents LPS-induced inflammation. However, little is known about the underlying mechanisms.. The binding affinity of shikonin to MD2 was analysed using computer docking, surface plasmon resonance analysis and elisa. In vitro, the anti-inflammatory effect and mechanism of shikonin were investigated through elisa, real-time quantitative reverse transcription PCR, Western blotting and immunoprecipitation assay. In vivo, lung injury was induced by intratracheal administration of LPS and assessed by changes in the histopathological and inflammatory markers. The underlying mechanisms were investigated by immunoprecipitation in lung tissue.. Shikonin directly bound to MD2 and interfered with the activation of toll-like receptor 4 (TLR4) induced by LPS. In cultured macrophages, shikonin inhibited TLR4 signalling and pro-inflammatory cytokine production. These effects were produced through suppression of key signalling proteins including the NF-κB and the MAPK pathway. We also showed that shikonin inhibits MD2-TLR4 complex formation and reduces LPS-induced inflammatory responses in a mouse model of ALI.. Our studies have uncovered the mechanism underlying the biological activity of shikonin in ALI and suggest that the targeting of MD2 may prove to be beneficial as a treatment option for this condition.

Topics: Acute Lung Injury; Animals; Cytokines; Humans; Inflammation; Lipopolysaccharides; Lymphocyte Antigen 96; MAP Kinase Signaling System; Mice; Molecular Docking Simulation; Naphthoquinones; Toll-Like Receptors

Shikonin, an analog of naphthoquinone pigments isolated from the root of Lithospermum erythrorhyzon, was recently reported to exert beneficial anti-inflammatory effects both in vivo and in vitro. The present study aimed to investigate the potential therapeutic effect of shikonin in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Dexamethasone was used as a positive control to evaluate the anti-inflammatory effect of shikonin in the study. Pretreatment with shikonin (intraperitoneal injection) significantly inhibited LPS-induced increases in the macrophage and neutrophil infiltration of lung tissues and markedly attenuated myeloperoxidase activity. Furthermore, shikonin significantly reduced the concentrations of TNF-α, IL-6 and IL-1β in bronchoalveolar lavage fluid induced by LPS. Compared with the LPS group, lung histopathologic changes were less pronounced in the shikonin-pretreated mice. Additionally, Western blotting results showed that shikonin efficiently decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα. These results suggest that shikonin exerts anti-inflammatory properties in LPS-mediated ALI, possibly through inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. Shikonin may be a potential agent for the prophylaxis of ALI.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Lipopolysaccharides; Lithospermum; Lung; Male; Mice; Mice, Inbred BALB C; Naphthoquinones; NF-kappa B; Organ Size; Plant Roots; Signal Transduction

Shikonin, a natural naphthoquinone pigment extracted from the root of Lithospermum erythrorhizon, has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of shikonin in acute lung injury induced by lipopolysaccharide (LPS) in mice.. Sixty male BALB/C mice were randomly allocated into six groups (n = 10, each): control group, shikonin group (50 mg/kg), LPS group, and three different doses (12.5, 25, and 50 mg/kg) for shikonin-treated groups. Shikonin or vehicle was given with an intragastric administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge.. Shikonin pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by shikonin pretreatment. Moreover, shikonin decreased the productions of the proinflammatory cytokines including tumor necrosis factor alpha and interleukin 1β and the concentration of total proteins in the bronchoalveolar lavage fluid. Shikonin pretreatment also reduced the concentrations of myeloperoxidase and nitric oxide in lung tissues. In addition, shikonin pretreatment significantly suppressed LPS-induced activation of cyclooxygenase 2 and inducible nitric oxide synthase and the nuclear factor κB DNA-binding activity in lung tissues.. This study indicates that shikonin may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may attribute partly to the inhibition of inducible nitric oxide synthase and cyclooxygenase 2 expression by downregulating nuclear factor κB activation.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchoalveolar Lavage Fluid; Cyclooxygenase 2; DNA; Drugs, Chinese Herbal; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred BALB C; Naphthoquinones; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Peroxidase; Pulmonary Edema