Soy isoflavone phyto-pharmaceuticals in interleukin-6 affections: Multi-purpose nutraceuticals at the crossroad of hormone replacement, anti-cancer and anti-inflammatory therapy
Section snippets
Soy isoflavone phyto-pharmaceuticals
Numerous botanical species and plant parts contain a diverse array of polyphenolic non-steroidal phyto-chemicals that are synthesized as floral pigments for the attraction of insect pollinators and as signal molecules for beneficial micro-organisms in the rhizosphere. Besides these functions, they also have a role as anti-microbial/fungal defense compounds, and furthermore afford photoprotection [1].
Based on their chemical structure, phenolic phyto-estrogens can be classified into four main
Health-beneficial effects of isoflavones
Impetus to the scientific inquiry into phyto-pharmaceutical effects is given by the epidemiological observation of striking historical and/or ethnic differences in hormone-related cancer rates and menopausal ailments [47], [50], [51]. The highest incidences of these cancers, menopausal symptoms as well as cardiovascular diseases are typically found in populations with western lifestyle, which include relatively high fat, meat-based and low-fiber diets [52]. Asian populations, however, with
IL6 physiology and pathology
The process of an inflammatory response to invading pathogens or damaging insults is of critical importance to the homeostasis of the human body. As this physiological inflammatory reaction, based on innate or adaptive immunity, determines health or illness, it needs to be precisely controlled by various feedback mechanisms [93], [94], [95], [96]. As such, balanced inflammation consequently allows acute timely effects but no accelerated overreaction or chronic responses. Furthermore,
NF-κB at the interface of inflammation and tumorigenesis: a paradigm for phyto-pharmaceuticals
A key player in IL6 gene expression is the transcription factor NF-κB, of which the transcriptional activity is regulated at multiple levels [99], [132], [133], [134], [135]. The NF-κB/IκB family of transcriptional regulators modulate the expression of a few hundred target genes, the majority of which participate in host immune responses [136], [137], [138], [139]. Gene knock-out and other studies not only establish roles for NF-κB in the ontogeny of the immune system, but also demonstrate that
IL6 gene regulation, HRT and “inflamm-ageing”
Transcription and expression of the multifunctional IL6 cytokine gene is tightly regulated at the level of its promoter, which acts as a sophisticated biosensor for environmental stress, thus controlling the above-described immunological homeostasis [99]. IL6 is normally expressed at low levels, except during infection, trauma, ageing or other stress conditions, upon which it can be secreted by various cell types, including endothelial cells, B-cells, T-cells, macrophages, dendritic cells, and
Nutrigenomics: the next frontier in nutraceutical therapy?
Progress in the battle against ageing disease and suffering is being accelerated by the availability of genomic information for humans, mice and other organisms. The interface between the nutritional environment and cellular/genetic processes is being referred to as “nutrigenomics”. Nutrigenomics seeks to provide a molecular genetic understanding of how common dietary chemicals (i.e. nutrition) affect health by altering the expression and/or structure of an individual’s genetic make-up. This in
Acknowledgements
This research was supported by the Interuniversitaire Attractiepolen (IUAP) and the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO). Nathalie Dijsselbloem is a fellow with the Vlaams Instituut voor de Bevordering van het Wetenschappelijk-Technologisch Onderzoek in de Industrie (IWT). Wim Vanden Berghe is a postdoctoral fellow with the FWO.
References (279)
- et al.
Flavonoids and isoflavonoids—a gold mine for metabolic engineering
Trends Plant Sci
(1999) - et al.
Characteristics and occurrence of phenolic phytochemicals
J Am Diet Assoc
(1999) The biochemistry and medical significance of the flavonoids
Pharmacol Ther
(2002)- et al.
Genistein
Phytochemistry
(2002) Therapeutic potential of selective estrogen receptor modulators
Curr Opin Chem Biol
(1998)What pharmacologists can learn from recent advances in estrogen signalling
Trends Pharmacol Sci
(2003)- et al.
Update on estrogen signaling
FEBS Lett
(2003) - et al.
A dynamic structural model for estrogen receptor-alpha activation by ligands, emphasizing the role of interactions between distant A and E domains
Mol Cell
(2002) - et al.
Phytoestrogens as modulators of steroid action in target cells
J Chromatogr B Anal Technol Biomed Life Sci
(2002) The secrets of selective estrogen receptor modulation: cell-specific coregulation
Cancer Cell
(2002)