Mechanisms and efficacy of immunobiologic therapies for inflammatory bowel diseases.

Current advances in understanding of the pathogenesis of inflammatory bowel disease have encouraged the development of many new therapies targeted at specific and non-specific mediators of the inflammatory bowel disease inflammatory pathway. Crohn's disease and ulcerative colitis, two common inflammatory bowel diseases likely result from interaction of multiple genetic and environmental risk and protective factors, deregulation of mucosal immunity in gut and breakdown of delicate balance of proinflammatory and anti-inflammatory cytokines. Immunobiologic agents targeted against TNF, leukocyte adhesion, Th1 polarization, T cell activation, nuclear factor-kappaB (NF-kappaB), and others are being assessed and will open exciting perspectives on development of therapies for inflammatory bowel disease.

Risk of gastric cancer is associated with the MUC1 568 A/G polymorphism.

Identifying the genetic variants that alter MUC1 protein expression may further our understanding of the risk for development of gastric cancer (GC). We used PCR-SSPs to identify the genotype of MUC1 A/G polymorphism at its 568 site of exon 2 and immunohistochemistry to detect MUC1 protein expression in GC patients and non-cancer subjects and analyzed the association between this polymorphism and MUC1 protein expression. We found that the frequency of AA genotype was significantly high in the GC patients and the risk for GC in AA genotype carriers increased 1.81-fold. Moreover, we found a significant underexpression of MUC1 protein in GC as compared to non-cancer subjects, which was negatively correlated to AA genotype of MUC1 (r=-0.1790, P=0.004). Furthermore, this study provides a possible mechanistic insight that the MUC1 A/G polymorphism at its 568 site disrupts the physiological functions of MUC1 which is important to the physiological protection of gastric mucosa. Thus we have provided evidence that may identify the MUC1 A/G polymorphism at 568 site, as a potential genetic factor which leads to an increase in susceptibility for GC through alteration of MUC1 gene and MUC1 expression in the population that carry the A allele.

Inhibition of COXs and 5-LOX and activation of PPARs by Australian Clematis species (Ranunculaceae).

The species of Clematis (Ranunculaceae) have been traditionally used for inflammatory conditions by indigenous Australians. We have previously reported that the ethanol extract of Clematis pickeringii inhibited COX-1. In this study, we examined the ethanol extracts and fractions of three Clematis species, Clematis pickeringii, Clematis glycinoides and Clematis microphylla, on cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). We further examined the activating effects on the protein expression of peroxisome proliferator-activated receptor alpha (PPARalpha) and gamma (PPARgamma) in HepG2 cells. The ethanol extracts of three Clematis species inhibited the activities of COX-1, COX-2 and 5-LOX in the different extents. The stem extract of Clematis pickeringii showed the highest inhibitory activities among the three species on COX-1, COX-2 and 5-LOX with the IC(50) values of 73.5, 101.2 and 29.3 microg/mL. One of its fractions also significantly elevated PPARalpha expression by 173, 280 and 435% and PPARgamma expression by 140, 228 and 296% at 4, 8 and 16 microg/mL, respectively.

Anti-inflammatory activity, cytotoxicity and active compounds of Tinospora smilacina Benth.

Tinospora smilacina Benth. has been used in Australian indigenous medicine for the treatment of headache, rheumatoid arthritis and other inflammatory disorders. As part of an investigation into the anti-inflammatory potential of plants using an ethnopharmacological approach, the present study sought to evaluate the efficacy and safety of Tinospora smilacina. An ethanol extract of this plant was evaluated in vitro for anti-inflammatory activities on cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LO) and phospholipase A(2) (PA(2)). The ethanol extract of Tinospora smilacina showed inhibitory activities on COX-1, COX-2, 5-LO and PA(2) with the IC(50) values of 63.5, 81.2, 92.1 and 30.5 micro g/mL respectively. Cytotoxic effect of the extracts of Tinospora smilacina was investigated in vitro using ATP-based luminescence assay and the results showed no cytotoxic effect on cell lines of skin fibroblasts (1BR3), human Caucasian hepatocyte carcinoma (Hep G2) and human Caucasian promyelocytic leukaemia (HL-60). This paper also describes the results of fractionations and bioassay guided chemical studies, suggesting that the anti-inflammatory activity is due to triterpene-fatty acid esters and free fatty acids.

A cross-cultural study: anti-inflammatory activity of Australian and Chinese plants.

In this study, in vitro inhibitory effects of 33 ethanol extracts obtained from 24 plant species (representing 11 different families) on cyclooxygenase-1 (COX-1) were evaluated. The plant materials selected for this study have been used in aboriginal medicine in Australia and traditional medicine in China for the treatment of various diseases that are considered as inflammation in nature, e.g. asthma, arthritis, rheumatism, fever, edema, infections, snakebite and related inflammatory diseases. All of the selected plants, with one exception, showed inhibitory activity against COX-1, which supports their traditional uses. The most potent COX-1 inhibition were observed from the extracts of Acacia ancistrocarpa leaves (IC(50)=23 microg/ml). Ficus racemosa bark, Clematis pickeringii stem, Acacia adsurgens leaves, Tinospora smilacina stem and Morinda citrifolia fruit powder exhibited inhibition of COX-1 with the IC(50) of 100, 141, 144, 158 and 163 microg/ml, respectively. Aspirin and indomethacin used as the reference COX-1 inhibitors in this study inhibited COX-1 with IC(50) of 241 and 1.2 microg/ml, respectively. The findings of this study may explain at least in part why these plants have been traditionally used for the treatment of inflammatory conditions in Australian aboriginal medicine and traditional Chinese medicine.