Overexpression of manganese superoxide dismutase in human dermal fibroblasts enhances the contraction of free floating collagen lattice: implications for ageing and hyperplastic scar formation.

Cell-matrix interactions are of significant importance for tissue homeostasis of the skin and, if disturbed, may lead to ageing and hyperplastic scar formation. We have studied fibroblasts stably overexpressing manganese superoxide dismutase (MnSOD) with a defined capacity for the removal of superoxide anions and concomitant accumulation of hydrogen peroxide to evaluate the role of enhanced MnSOD activity on the dynamics of cell-matrix interactions in the three-dimensional collagen lattice contraction assay. MnSOD overexpressing fibroblast populated collagen lattices revealed a significantly enhanced contraction compared to collagen lattices populated with vector control cells. The enhanced collagen lattice contraction was in part due to an increase in active TGF-beta1 and the accumulation of H2O2 in MnSOD overexpressing fibroblasts populated collagen lattices. Inhibition of TGF-beta1 signalling by the ALK4,5,7 kinases' inhibitor SB431542 at least partly inhibited the enhanced collagen lattice contraction of MnSOD overexpressing fibroblasts populated lattices. In addition, supplementation of vector control fibroblast populated collagen lattices with recombinant TGF-beta1 concentration dependently enhanced the collagen lattice contraction. In the presence of the antioxidant Ebselen, a mimic of H2O2 and other hydroperoxides/peroxynitrite-detoxifying glutathione peroxidase, collagen lattice contraction and the activation of TGF-beta1 were significantly reduced in collagen lattices populated with MnSOD overexpressing fibroblasts. Collectively, these data suggest that H2O2 or other hydroperoxides or peroxynitrite or a combination thereof may function as important second messengers in collagen lattice contraction and act at least in part via TGF-beta1 activation.

The use of neem for controlling gastric hyperacidity and ulcer.

H(2)-receptor blockers and proton pump inhibitors are now used extensively to control gastric and duodenal ulcer, inflammation and pain, but these drugs have limitations and are not always affordable. The development of novel nontoxic antiulcer drugs, including from medicinal plants, is therefore desirable, and Azadirachta indica A. Juss, commonly known as Neem, is known to have potent gastroprotective and antiulcer effects. This review deals with the pharmacological and biochemical studies carried out regarding the antiulcer activities of Neem extracts and their mechanism of action, including the inhibition of acid secretion. A comparison with ranitidine and omeprazole in some animal models has been included and clinical studies, where available, have also been incorporated, along with a safety evaluation. Neem bark extract has the potential for the development of novel medicines for the therapeutic control of gastric hyperacidity and ulcer.

Biological activities of crude extracts and chemical constituents of Bael, Aegle marmelos (L.) Corr.

Bael (Aegle marmelos (L.) Corr.) is an important medicinal plant of India. Leaves, fruits, stem and roots of A. marmelos have been used in ethno medicine to exploit its' medicinal properties including astringent, antidiarrheal antidysenteric, demulcent, antipyretic and anti-inflammatory activities. Compounds purified from bael have been proven to be biologically active against several major diseases including cancer, diabetes and cardiovascular diseases. Preclinical studies indicate the therapeutic potential of crude extracts of A. marmelos in the treatment of many microbial diseases, diabetes and gastric ulcer. This review covers the biological activities of some isolated chemical constituents of A. marmelos and preclinical studies on some crude extracts and pure compounds to explore novel bioactive compounds for therapeutic application.