Many clinical studies have been carried out to determine the health benefits of soy protein and the isoflavones contained in soy. S-equol is not present in soybeans but is produced naturally in the gut of certain individuals, particularly Asians, by the bacterial biotransformation of daidzein, a soy isoflavone. In those intervention studies in which plasma S-equol levels were determined, a concentration of >5-10 ng/mL has been associated with a positive outcome for vasomotor symptoms, osteoporosis (as measured by an increase in bone mineral density), prostate cancer, and the cardiovascular risk biomarkers low-density lipoprotein cholesterol and C-reactive protein. These studies suggest that S-equol may provide therapeutic benefits for a number of medical needs.
We have evaluated the properties of a new class of anti-inflammatory agents derived from capsaicin, using the analogs NE-19550 (N-vanillyloleamide) and NE-28345 (N-oleyl-homovanillamide) as examples. This class displayed an atypical profile in the assays utilized, including 1) anti-edema and antileukocyte migration activity in the rat carrageenan pleurisy assay without suppression of pleural prostanoid synthesis, 2) blockade of human platelet aggregation induced by arachidonate or PAF but not that induced by the PGH2 analog U-46619, without equivalent inhibition in vitro of mammalian cyclooxygenase or thromboxane synthetase preparations, 3) greater potency and efficacy in the rat implanted sponge assay than in the adjuvant arthritis assay, without inhibition of LTB4 or 15-HETE synthesis in vitro, 4) stronger topical activity in the mouse croton oil inflamed ear assay than the guinea pig UV erythema assay, and 5) oral activity in the rat carrageenan paw edema assay and mouse phenylquinone abdominal constriction rest combined with failure to induce gastric erosion in rats at therapeutic doses. We conclude that NE-19550 and NE-28345 do not act like conventional NSAIDs via suppression of arachidonic acid metabolism.
Oestrogen (17b estradiol) and the dietary antioxidants resveratrol, genistein and S-equol, an isoflavone produced from the gut biotransformation of soy daidzein, are effective agents to reduce ageing in skin. It is widely held that these antioxidants scavenge free radicals to prevent skin damage. However, the evidence to date suggests that the primary mechanism of action of these antioxidants is to activate oestrogen receptor b (ERb), which in turn enhances the expression of antioxidant enzymes and inhibits the expression of snail, a transcription factor that regulates keratinocyte cell proliferation and migration. Based on their selectivity, ERb agents provide a treatment option for ageing skin without the potential safety issues associated with oestrogen therapy.Key words: AP-1 -oestrogen receptor b -photoaging -resveratrol -S-equol Accepted for publication 8 August 2011Ageing skin: scope of the problem 'Old age isn't so bad when you consider the alternative' (Maurice Chevalier-New York Times, 9 October 1960). Although ageing skin has minimal effects on long-term health, more than $50 billion a year is spent on skin products, which claim to prevent or reverse the ageing process. Although the skin is the largest organ in the body, it is one of the least studied and we know very little about the changes that occur with ageing. It is known that oestrogen plays a key role in ageing skin. In this viewpoint, we present the evidence for a selective oestrogen receptor b (ERb) agonist as an agent to prevent the ageing process.Reactive oxygen activates transcription factors AP-1 and snail in skin Fine wrinkles, dry skin, hair loss and hyperpigmented spots are early indications of skin ageing. The accumulation of collagen breakdown products is a hallmark of ageing skin and results in a decrease in mechanical tension that leads to wrinkles (1). Agerelated differences in the amount and structure of proteoglycans that bind to collagen also determine the mechanical properties of skin (2). There are multiple pathways (3) that can contribute to ageing skin, presenting a challenge for treatment. Both natural skin ageing and photoageing owing to exposure to the sun generate the superoxide radical (O 2 ·) that activates the transcription factor AP-1 (Fig. 1). This transcription factor consists of heterodimers of c-Jun and c-Fos. Phosphorylation of c-Jun by mitogenactivated protein kinases (MAP kinases) leads to increased AP-1 activity (4); retinoids, a mainstay for the treatment of photoageing, inhibit the activation of c-Jun. Activated AP-1 binds to the promoter region of the procollagen gene to inhibit its transcription, thus reducing the amount of collagen in skin. AP-1 also activates the matrix metalloproteinase genes MMP-1 (collagenase), MMP-3 (stromelysin) and MMP-9 (gelatinase), enzymes that degrade collagen (5). Another protein that is induced with UV irradiation through AP-1 is snail (6), a transcription factor that plays an important role in the epithelial-to-mesenchymal transition (EMT), promoting keratinocyt...
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