Genistein and phycocyanobilin may prevent hepatic fibrosis by suppressing proliferation and activation of hepatic stellate cells

Hepatic fibrosis reflects hepatotoxin-mediated activation of hepatic stellate cells, resulting in their proliferation and transformation to myofibroblasts that secrete collagen. This activation is suppressed by estrogen, an effect which explains the decreased risk for hepatic fibrosis enjoyed by premenopausal women and by postmenopausal women receiving hormone replacement therapy. Since stellate cells have been found to express the beta but not the alpha isoform of the estrogen receptor, it can be predicted that nutritional intakes of the soy isoflavone genistein - a selective agonist for ERbeta in the low nanomolar plasma concentrations achievable with these intakes - have potential for suppressing hepatic fibrosis, in both men and women. The antiproliferative impact of estrogen on stellate cells is mediated at least in part by suppression of NADPH oxidase activity; oxidant production by this enzyme complex plays a crucial role in stellate cell activation. Alternatively, it may be feasible to inhibit NADPH oxidase with phycocyanobilin (PCB), a biliverdin homolog found in spirulina that has recently been shown to inhibit the NADPH oxidase activity of human cell cultures in low micromolar concentrations. joint administration of soy isoflavones and PCB in appropriate doses might have considerable potential for prevention of hepatic fibrosis in at-risk subjects. (C) 2008 Elsevier Ltd. All rights reserved.