Deng Xuming

Geniposide, an Iridoid Glucoside Derived from Gardenia jasminoides, Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice

Geniposide, a main iridoid glucoside component of gardenia fruit, has been shown to possess anti-inflammatory activity. However, its potential use for acute lung injury (ALI) has not yet been studied. The aim of this study was to evaluate the anti-inflammatory properties of geniposide using a mouse ALI model. ALI was induced by intranasal injection of lipopolysaccharide (LPS). Pretreatment of mice with geniposide (20, 40, or 80 mg/kg) resulted in a marked reduction in inflammatory cells and total protein concentration in the bronchoalveolar lavage fluid (BALF) of mice. Levels of inflammatory mediators, including tumour necrosis factor- α (TNF- α), interleukin-6 (IL-6), and interleukin-10 (IL-10), were significantly altered after treatment with geniposide. Histological studies using hematoxylin and eosin (H&E) staining demonstrate that geniposide substantially inhibited LPS-induced alveolar wall changes, alveolar haemorrhage, and neutrophil infiltration in lung tissue, with evidence of reduced myeloperoxidase (MPO) activity. In addition, we investigated potential signal transduction mechanisms that could be implicated in geniposide activity. Our results suggest that geniposide may provide protective effects against LPS-induced ALI by mitigating inflammatory responses and that the compounds mechanism of action may involve blocking nuclear factor-kappaB (NF- κB) and mitogen-activated protein kinases (MAPK) signalling pathway activation.

Immunosuppressive Activity of Florfenicol on the Immune Responses in Mice

Florfenicol is a new type of broad-spectrum antibacterial that has been used in veterinary clinics. It shows immunosuppressive activity on the immune responses to ovalbumin (OVA) in mice. In the present study, florfenicol suppressed lipopolysaccharide (LPS)-stimulated splenocyte proliferation in a concentration-dependent manner in vitro and in vivo. BALB/c mice were immunized subcutaneously with OVA on days 1 and 4. Following the second immunization, mice were treated with a single daily oral dose of florfenicol (50, 100, and 200 mg/kg) for 10 consecutive days. On day 14, blood samples were collected to analyze OVA-specific IgG, IgG1, and IgG2b antibodies, and splenocytes were harvested to assess lymphocyte proliferation, CD3+ T and CD19+ B lymphocyte subsets. The results presented here demonstrate that florfenicol not only significantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation but also decreased the percentage of CD19+ B cells in a dose-dependent manner and suppressed CD3+ T cell at high doses. Moreover, OVA-specific IgG, IgG1 and IgG2b titers in OVA-immunized mice were reduced by florfenicol. These results suggest that florfenicol could suppress humoral and cellular immune responses in mice.

Florfenicol inhibits allergic airway inflammation in mice by p38 MAPK-mediated phosphorylation of GATA 3

Florfenicol has been shown to possess anti-inflammatory activity. However, its possible use for asthma has not yet been studied. First we investigated the anti-inflammatory properties of florfenicol using mice asthma model. BALB/c mice were immunized and challenged by ovalbumin. Treatment with florfenicol caused a marked reduction in inflammatory cells and three Th2 type cytokines in the bronchoalveolar lavage fluids of mice. The levels of ovalbumin-specific IgE and airway hyperresponsiveness were significantly altered after treatment with florfenicol. Histological studies using H&E and AB-PAS staining demonstrate that florfenicol substantially inhibited ovalbumin-induced inflammatory cells infiltration in lung tissue and goblet cell hyperplasia in the airway. These results were similar to those obtained with dexamethasone treatment. We then investigated which signal transduction mechanisms could be implicated in florfenicol activity. Our results suggested that the protective effect of florfenicol was mediated by the inhibition of the p38 MAPK-mediated phosphorylation of GATA 3.