Forsythoside A inhibits adhesion and migration of monocytes to type II alveolar epithelial cells in lipopolysaccharide-induced acute lung injury through upregulating miR-124.

Acute lung injury (ALI) is a severe disease for which effective drugs are still lacking at present. Forsythia suspensa is a traditional Chinese medicine commonly used to relieve respiratory symptoms in China, but its functional mechanisms remain unclear. Therefore, forsythoside A (FA), the active constituent of F. suspensa, was studied in the present study. Inflammation models of type II alveolar epithelial MLE-12 cells and BALB/c mice stimulated by lipopolysaccharide (LPS) were established to explore the effects of FA on ALI and the underlying mechanisms. We found that FA inhibited the production of monocyte chemoattractant protein-1 (MCP-1/CCL2) in LPS-stimulated MLE-12 cells in a dose-dependent manner. Moreover, FA decreased the adhesion and migration of monocytes to MLE-12 cells. Furthermore, miR-124 expression was upregulated after FA treatment. The luciferase report assay showed that miR-124 mimic reduced the activity of CCL2 in MLE-12 cells. However, the inhibitory effects of FA on CCL2 expression and monocyte adhesion and migration to MLE-12 cells were counteracted by treatment with a miR-124 inhibitor. Critically, FA ameliorated LPS-induced pathological damage, decreased the serum levels of tumor necrosis factor-α and interleukin-6, and inhibited CCL2 secretion and macrophage infiltration in lungs in ALI mice. Meanwhile, administration of miR-124 inhibitor attenuated the protective effects of FA. The present study suggests that FA attenuates LPS-induced adhesion and migration of monocytes to type II alveolar epithelial cells though upregulating miR-124, thereby inhibiting the expression of CCL2. These findings indicate that the potential application of FA is promising and that miR-124 mimics could also be used in the treatment of ALI.

Glycyrrhizin Ameliorates Radiation Enteritis in Mice Accompanied by the Regulation of the HMGB1/TLR4 Pathway.

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients' tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF-α in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1ß, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1ß, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.

Antioxidant and Antiapoptotic Polyphenols from Green Tea Extract Ameliorate CCl4-Induced Acute Liver Injury in Mice.

OBJECTIVE: To investigate the phenolic composition, antioxidant properties, and hepatoprotective mechanisms of polyphenols from green tea extract (GTP) in carbon tetrachloride (CCl4)-induced acute liver injury mouse model. METHODS: High-performance liquid chromatography was used to analyze the chemical composition of the extract. Antioxidant activity of GTP was assessed by O2∙-, OH∙, DPPH∙, and ferric-reducing antioxidant power (FRAP) assay in vitro. Sixty Kunming mice were divided into 6 groups including control, model, low-, medium-, and high-doses GTP (200, 400, 800 mg/kg) and vitamin E (250 mg/kg) groups, 10 in each group. GTP and vitamin E were administered at a level of abovementioned doses twice per day for 7 days prior to exposure to a single injection of CCl4. Hepatoprotective effects of GTP were evaluated in a CCl4-induced mouse model of acute liver injury, using commercial enzyme linked immunosorbent assay kits, histopathological observation, terminal deoxynucleotidyl transferase-mediated dUTPNick-end labeling (TUNEL) assay and Western blot. RESULTS: GTP contained 98.56 µg gallic acid equivalents per milligram extract total polyphenols, including epicatechingallate, epigallocatechin gallate, epicatechin, and epigallocatechin. Compared with the model group, low-, medium-, or high doses GTP significantly decreased serum levels of alanine aminotransferase and aspartate transaminase (P<0.01). Histopathological observation confirmed that pretreatment of GTP prevented swelling and necrosis in CCl4-exposed hepatocytes. Hepatoprotective effects of low-, medium-, and high-dose GTP were associated with eliminating free radicals and improving superoxide dismutase, catalase, and glutathione peroxidase activity in the liver. Additionally, low-, medium-, and high-dose GTP decreased cell apoptosis in the CCl4-exposed liver (P<0.01). Phosphorylated nuclear factor kappa-B (NF-κB), p53, Bcl-2 associated x protein/B-cell lymphoma/leukemia-2 gene, cytochrome C, and cleaved caspase-3 levels were downregulated compared with the model group (P<0.01). CONCLUSION: GTP achieves hepatoprotective effects by improving hepatic antioxidant status and preventing cell apoptosis through caspase-3-dependent signaling pathways.