Inhibition of lipoxygenase by soy isoflavones: evidence of isoflavones as redox inhibitors

Hydroperoxides, the products of lipoxygenase mediated pathways, play a major role in the manifestation of chronic inflammatory diseases. Soy isoflavones act as antioxidants due to their ability to scavenge free radicals. Isoflavones inhibit the activity of soy lipoxygenase-1 and 5-lipoxygenase, from human polymorph nuclear lymphocyte in a concentration dependent manner. Spectroscopic and enzyme kinetic measurements have helped to understand the nature and mechanism of inhibition. Genistein is the most effective inhibitor of soy lipoxygenase 1 and 5-lipoxygenase with IC(50) values of 107 and 125 microM, respectively. Genistein and daidzein are noncompetitive inhibitors of soy lipoxygenase 1 with inhibition constants, K(i), of 60 and 80 microM, respectively. Electron paramagnetic resonance and spectroscopic studies confirm that isoflavones reduce active state iron to ferrous state and prevent the activation of the resting enzyme. A model for the inhibition of lipoxygenase by isoflavones is suggested.     

Metabolism of isoflavones in human subjects

Isoflavones form a group of plant compounds that occur mainly in legumes, soy being the most important source in human diet. The high levels of isoflavones in the diet have been associated with a lowered risk for hormone-dependent diseases, including breast and prostate cancers, osteoporosis and cardiovascular disease. The metabolism of isoflavones in humans has been studied to a certain extent, but detailed studies are lacking. This paper reviews the current knowledge on metabolism of isoflavones and presents some preliminary results of a comprehensive soy feeding study, in which the phase I metabolites of soy isoflavones, daidzein, genistein and glycitein, were identified by GC-MS. This revised version was published online in June 2006 with corrections to the Cover Date.     

New isoflavones from Ceiba pentandra

Two new isoflavones, pentandrin (1) and pentandrin glucoside (2), were isolated from the stem barks of Ceiba pentandra along with beta-sitosterol and its 3-O-beta-D-glucopyranoside, which was isolated for the first time from this plant. The structures of these compounds were elucidated with the help of spectroscopic techniques, while the structure of 1 was unambiguously confirmed by single-crystal X-ray diffraction studies.     

Soy isoflavones and cellular mechanics

Soy isoflavones are diphenolic compounds that are frequently used for alternative treatment of ageing symptoms in both genders. They operate at principally two hierarchical levels of functional organization – cellular and molecular, while these ‘types’ of action appear to have indefinite borders. Soy isoflavone action at the cellular level involves inter alia the effects on cell mechanics. This epigenetic and modular determinant of cell function and fate is defined by: the anchorage to extracellular matrix (ECM) and neighboring cells, cytoskeleton organization, membrane tension and vesicle trafficking. Soy isoflavones have been reported to: (i) generally fashion an inert cell phenotype in some cancers and enhance the cell anchorage in connective tissues, via the effects on ECM proteins, focal adhesion kinases-mediated events and matrix metalloproteinases inhibition; (ii) affect cytoskeleton integrity, the effects being related to Ca²⁺ ions fluxes and involving cell retraction or differentiation/proliferation-related variations in mechanical status; (iii) increase, remain “silent” or decrease membrane tension/fluidity, which depends on polarity and a number and arrangement of functional groups in applied isoflavone; (iv) provoke inhibitory effects on vesicle trafficking and exo-/endocytosis, which are usually followed by changed cell morphology. Here we present and discuss the abundance of effects arising from cells’ “encounter” with soy isoflavones, focusing on different morphofunctional definers of cell mechanics.     

Two isoflavones from Juniperus Macropoda

Two new isoflavones, junipegenin-B and -C, have been isolated from ethanolic extracts of Juniperus macropoda and their structures assigned. One of them, junipegenin-C, has been synthesized from iridin.     

Soy isoflavones and cognitive function

There is growing interest in the physiological functions of soy isoflavones, especially in whether they affect cognitive function and have beneficial effects on neurodegenerative diseases. Here we review the recent evidence from clinical and experimental studies supporting a role for soy isoflavones in cognitive function. Soy isoflavones may mimic the actions and functions of estrogens on brain, and they have been shown to have positive effects on the cognitive function in females; however, studies on their effects on spatial memory have not provided consistent results in males. Although data from humans, cultures, and animal models are currently insufficient for elucidating the metabolism of soy isoflavone actions on cognitive function and the nervous system, we suggest two putative pathways; (1) an estrogen receptor-mediated pathway and (2) via the inhibition of tyrosine kinase, in particular by genistein, which is one of the soy isoflavones. Although soy isoflavones appear to have a positive effect on brain function, further research is needed to determine not only the efficacy but also the safety of soy isoflavones on the nervous system and cognitive function.     

Bioavailability of phenolic acids

Two large classes of phenolic acids were comprised in this review: benzoic acid derivatives and cinnamic acid derivatives. They have been found to be very extended in fruits and vegetables at different concentrations. For example, hydroxycinnamic acids concentration was higher than that found for hydroxybenzoic acids. Concerning their consumption, hydroxycinnamic acids provide larger contributions to the total polyphenol intake than benzoic acid derivatives or flavonoids. This phenolic acid intake is led by the coffee intake since it has very rich concentrations in hydroxycinnamic acids. Moreover, several experimental and epidemiological studies report the protection of phenolic acids against various degenerative diseases. However, despite all these interesting attributions and even if phenolic acids are the main polyphenols consumed, their bioavailability has not received as attention as that flavonoids. This concept is an essential step to understand the health-promoting properties of phenolic acids and to serve as tool to design in vivo and in vitro experiments to know their biological properties. Therefore, a compilation of bioavailability data of phenolic acids have been presented here paying attention to the two types of phenolic acid bioavailability, direct and indirect derived from the direct phenolic acid and flavonoid consumption, respectively. Then, a new relevant concept which may be named as total bioavailability of phenolic acids includes the direct absorption and metabolism of phenolic acids from food consumption and phenolic acids bioavailability as a result of the cleavage on the main skeleton ring of flavonoids by the gut microflora.     

New prenylated isoflavones from Millettia pachycarpa

Isolation of four new isoflavones from a new collection of Millettia pachycarpa is reported. Proof of the structure of lupinifolol, previously isolated from M. pachycarpa, by synthesis of dehydrolupinifolol is described.     

Cytotoxic isoflavones from Erythrina indica.

Bioassay-directed fractionation of the CH(2)Cl(2)-MeOH (1:1) extract of the stem bark of Erythrina indica, has resulted in the isolation of two new isoflavone derivatives named indicanines D and E together with 11 known compounds including: six isoflavones (genistein, wighteone, alpinumisoflavone, dimethylalpinumisoflavone, 8-prenyl erythrinin C, and erysenegalensein E), one cinnamate (erythrinassinate B), two pentacyclic triterpenes (oleanolic acid and erythrodiol), and two phytosterols (stigmasterol and its 3-O-beta-D-glucopyranoside). The structures of the new compounds were elucidated by means of spectroscopic analysis. The in vitro cytocidal activity against KB cells of some of the isolated compounds is also reported.     

Formation of polyhydroxylated isoflavones from the soybean seed isoflavones daidzein and glycitein by bacteria isolated from tempe

Five tempe-derived bacterial strains identified as Micrococcus or Arthrobacter species were shown to transform the soybean isoflavones daidzein and glycitein to polyhydroxylated isoflavones by different hydroxylation reactions. All strains converted glycitein and daidzein to 6,7,4′-trihydroxyisoflavone (factor 2) and the latter substrate also to 7,8,4′-trihydroxyisoflavone. Three strains transformed daidzein to 7,8,3′,4′-tetrahydroxyisoflavone and 6,7,3′,4′-tetrahydroxyisoflavone. In addition, two strains formed 6,7,8,4′-tetrahydroxyisoflavone from daidzein. Conversion of glycitein by these two strains led to the formation of factor 2 and 6,7,3′,4′-tetrahydroxyisoflavone. The structures of these transformation products were elucidated by spectroscopic techniques and chemical degradation. Revision received: 9 September 1995 / Accepted: 21 September 1995     

大豆异黄酮微生物转化研究进展

大豆异黄酮是大豆在其生长过程中形成的一类次生代谢产物,具有抗氧化、抗癌、减少骨质流失、降低心脑血管发病率等多种生理功能。目前已知,被摄人机体的大豆异黄酮将被肠道微生物菌群转化为具有更高、更广生物学活性的不同产物。因此,大豆异黄酮对人体的有益调节作用强弱并不简单取决于摄人机体的净含量的多少,更在于被摄人机体的大豆异黄酮将如何被肠道菌群转化。本文从大豆异黄酮的组成与功能、大豆异黄酮体内吸收、代谢及微生物转化、转化产物的活性以及高效合成等方面进行了系统综述,对大豆异黄酮微生物生物转化研究现状和存在问题进行分析总结,并对今后发展趋势进行展望,旨在推动高活性大豆异黄酮微生物转化产物的研究与开发。     

Bioavailability of Sorbed 3-Chlorodibenzofuran

One of the main factors impeding the bioremediation of polluted soils, sediments, and aquifers is the low bioavailability of chemicals which are sorbed by organic matter. To obtain more insight into the factors that control the degradation of sorbed compounds, we used a defined model system in which 3-chlorodibenzofuran (3CDF) was the organic contaminant, porous Teflon granules were the sorbent, and Sphingomonas sp. strain HH19k was the test organism. The sorption of 3CDF to Teflon reached equilibrium within 150 min. The curved shape of the sorption isotherm, the extent of sorption, and the desorption kinetics suggested that there was a surface interaction (adsorption) between 3CDF and Teflon which took place mainly inside the pores of the granules. The kinetics of desorption could be ascribed to sorption-retarded radial diffusion inside the granules since the desorption rate not only was correlated with the sorbed-phase concentration, but also depended on the equilibration status of sorption, since (i) the high initial desorption rate sharply declined because of the depletion of 3CDF in the outermost parts of the granules, but high rates were observed again after the system had been given time to reequilibrate, and (ii) the initial desorption rate was higher when the preceding contact time between sorbate and sorbent was shorter (i.e., most 3CDF was still located in the exterior parts of the granules). These characteristics were observed irrespective of whether the desorption was driven by percolating water through the sorbent or by attaching active bacteria to the sorbent. 3CDF consumption by attached cells drove 3CDF desorption to a considerable extent. The attached cells were thus efficiently supplied with desorbing 3CDF. On the basis of our results, we propose that the rate at which a sorbed substrate becomes available for organisms is influenced by (i) the specific affinity of the degrading organisms (i.e., their ability to reduce the aqueous substrate concentration) and (ii) the tendency of the organisms to adhere to the sorbent.