Cornus iridoid glycoside alleviates sepsis-induced acute lung injury by regulating NF-κB and Nrf2/HO-1 pathways.

BACKGROUND: Sepsis-induced acute lung injury (ALI) is a syndrome associated with inflammation. Cornus iridoid glycoside (CIG), a bioactive component isolated from Corni Fructus, exhibits anti-inflammatory activities. However, the function and underlying mechanisms of CIG in mice with sepsis-induced ALI remain elusive. METHODS: The sepsis-elicited ALI model of mice was established by the induction of cecal ligation and puncture (CLP). The wet/dry (W/D) ratio of lung tissues was examined, and the pathological alterations were determined by hematoxylin and eosin staining. The messenger RNA (mRNA) expressions and serum levels of Interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent serologic assay, respectively. The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were assessed by biochemical kits. In addition, the relative protein levels of p-p65, p65, phosphorylated- nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (p-IκBα), IκBα, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) gene were analyzed by Western blotting analysis. RESULTS: CLP enhanced W/D ratio and aggravated pathological changes and scores in mice, which were obviously alleviated by the two concentrations of CIG treatment. CIG treatment notably decreased the CLP-induced mRNA expressions and serum levels of IL-1ß, IL-6, TNF-α, and MDA, but enhanced the decreased concentrations (caused by CLP) of SOD and GSH-Px. Moreover, CIG treatment significantly decreased the ratios of p65/p-p65 and IκBα/p-IκBα caused by CLP, but aggravated the CLP-induced relative protein levels of Nrf2 and HO-1. CONCLUSIONS: CIG obviously ameliorated the sepsis-induced ALI in mice by suppressing inflammation and oxidative stress, which was closely associated with nuclear factor kappa B (NF-κB) and Nrf2-HO-1 signaling pathways.

Acute and sub-chronic toxicological studies of the iridoid glycosides extract of Lamiophlomis rotata (Benth.) Kudo in rats.

Lamiophlomis rotata(Benth.) Kudo is widely used in traditional Chinese medicine and its iridoid glycosides extract (IGLR) was the main active ingredient with hemostatic, antinociceptive and anti-inflammatory effects. This study was aimed to evaluate the safety of IGLR using acute and sub-chronic toxicity study methods on Sprague-Dawley rats. In acute toxicity test, IGLR caused slight diarrhea in three dose groups and a decreased of RBC and increased of MCH and Ret (P < .05) were observed in 16 g/kg group. In sub-chronic toxicity study, unscheduled deaths occurred in 1 and 3 rats at 0.40 and 1.00 g/kg groups, respectively. A slight diarrhea was observed in 1.00 g/kg group. Hemolytic anemia was the main toxicity effects of IGLR found in 0.40 and 1.00 g/kg groups, with a significant decrease of RBC, HGB (P < .05) and increase of Ret, MCV, MCH (P < .05) in hematological parameters, a significant decrease of ALT, Crea (P < .05) and increase of TBIL (P < .05) in biochemical parameters, and a significant increase of the percentage of rubricyte, normoblast (P < .05) in bone marrow. Overall, this study found IGLR has a potential toxicity considering with hemolytic anemia and diarrhea to rat. These results provide an important reference for further IGLR-related drug exploration.

Cytocompatibility study of a natural biomaterial crosslinker--Genipin with therapeutic model cells.

Genipin has been widely used as a natural crosslinker to substitute chemical crosslinkers such as glutaraldehyde to crosslink various biomaterials like gelatin, collagen, and chitosan. However, there are contradicting views on the cytotoxicity and safety of genipin in tissue engineering. Therefore in this study, we aimed to evaluate the toxicity of genipin on skeletal tissues cells-osteoblasts and chondrocytes as they are also representatives of typical anchorage-dependent cells (ADCs) and nontypical ADCs. Results suggest that genipin toxicity is dose dependent and acute but not time dependent on both osteoblasts and chondrocytes. In particular, chondrocytes exhibit substantial alterations in the gene expression when exposed to Maximum nontoxic concentration (MaxNC) of genipin but there were no significant changes in the genes tested in osteoblasts. Since osteoblasts are typical ADCs, cellular focal adhesion assessment was carried out with F-actin being more contracted and unorganized when exposed to minimum toxic concentration (MinTC) of genipin. The mechanisms involved in cell deaths in both cell types are believed to be similar and hence using osteoblast as the model, cells were stained positive for Annexin-V and Reactive oxygen species (ROS) level were elevated at MinTC of genipin. Collectively, genipin induced cell apoptosis via ROS production, and apparently, gene expressions could also be altered at MaxNC. For this reason, we recommend the dose of genipin to be controlled within 0.5 mM.