Interest in the physiological role of the bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the class of compounds known as the phytoestrogens, which embody several groups of non‐steroidal oestrogens including isoflavones, lignans and stilbenes that are widely distributed within the plant kingdom. These compounds have a wide range of hormonal and non‐hormonal activities in animals or in vitro and these suggest plausible mechanisms for potential health effects of diets rich in these compounds in humans. In addition, experimental and epidemiological data are available to support the concept that phytoestrogen‐rich diets exert physiological effects, and preliminary human studies suggest a potential role for dietary phytoestrogens in affecting hormone‐dependent disease rates. © 2000 Society of Chemical Industry

Metabolic programming and metabolic imprinting describe early life events, which impact upon on later physiological outcomes. Despite the increasing numbers of papers and studies, the distinction between metabolic programming and metabolic imprinting remains confusing. The former can be defined as a dynamic process whose effects are dependent upon a critical window(s) while the latter can be more strictly associated with imprinting at the genomic level. The clinical end points associated with these phenomena can sometimes be mechanistically explicable in terms of gene expression mediated by epigenetics. The predictivity of outcomes depends on determining if there is causality or association in the context of both early dietary exposure and future health parameters. The use of biomarkers is a key aspect of determining the predictability of later outcome, and the strengths of particular types of biomarkers need to be determined. It has become clear that several important health endpoints are impacted upon by metabolic programming/imprinting. These include the link between perinatal nutrition, nutritional epigenetics and programming at an early developmental stage and its link to a range of future health risks such as CVD and diabetes. In some cases, the evidence base remains patchy and associative, while in others, a more direct causality between early nutrition and later health is clear. In addition, it is also essential to acknowledge the communication to consumers, industry, health care providers, policy-making bodies as well as to the scientific community. In this way, both programming and, eventually, reprogramming can become effective tools to improve health through dietary intervention at specific developmental points.Imprinting or programming as a result of early life experience is becoming an accepted scientific phenomenon. Implicit in this is the concept of a 'stage of developmental plasticity, where specific conditions give rise to later life outcomes'. The most significant aspect is metabolic imprinting, in which maternal undernutrition, obesity and diabetes during gestation and lactation can contribute towards obesity in the offspring (1) . Other endpoints that seem to be affected by early life exposure include neurodevelopment and immune modulation.The concept of fetal growth affecting adult disease was explained by Barker (2,3) in his seminal papers. Programming later evolved to mean alterations in nutrition and growth at specific developmental points, resulting in long-term or even permanent effects (4) . Observation is the first step and the initial link between health and early diet is often found from epidemiological investigations. One of the most exemplary studies is the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (5) . This has been the source for a host of publications in which early diet is linked to later obesity and to other health endpoints, as outlined in Table 1.Other cohorts include the Helsinki study, which showed a link between prenatal and postnatal factors and ...

Sortase A (SrtA) from Gram positive pathogens is an attractive target for inhibitors due to its role in the attachment of surface proteins to the cell wall. We found that the plant natural product trans-chalcone inhibits Streptococcus mutans SrtA in vitro and also inhibited S. mutans biofilm formation. Mass spectrometry revealed that the trans-chalcone forms a Michael addition adduct with the active site cysteine. The X-ray crystal structure of the SrtA H139A mutant provided new insights into substrate recognition by the sortase family. Our study suggests that chalcone flavonoids have potential as sortase-specific oral biofilm inhibitors.

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Phase II metabolising enzymes enable the metabolism and excretion of potentially harmful substances in adults, but to date it is unclear whether dietary phytochemicals can induce phase II enzymes differently between adults and infants. We investigated the expression of phase II enzymes in an in vitro model of primary skin fibroblasts at three different developmental stages, 1 month, 2 years and adult, to examine potential differences in age-related phase II enzymes in response to different phytochemicals (5-20 mM) including sulphoraphane, quercetin and catechin. Following phytochemical treatment, a significant increase in mRNA of glutathione S-transferase A1 (GSTA1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) was observed, with the most marked increases seen in response to sulphoraphane (3-10-fold for GSTA1, P¼ 0·001, and 6 -35-fold for NQO1, P¼ 0·001 -0·017). Catechin also induced 3 -5-fold changes in NQO1 transcription, whereas quercetin had less effect on NQO1 mRNA induction in infant cells. Moreover, NQO1 protein levels were significantly increased in 2-year-old and adult cell models in response to sulphoraphane treatment. These results suggest that metabolic plasticity and response to xenobiotics may be different in infants and adults; and therefore the inclusion of phytochemicals in the infant diet may modulate their induction of phase II metabolism, thereby providing increased protection from potentially harmful xenobiotics in later life.