Milk: A Natural Guardian for the Gut Barrier.

The gut barrier plays an important role in health maintenance by preventing the invasion of dietary pathogens and toxins. Disruption of the gut barrier can cause severe intestinal inflammation. As a natural source, milk is enriched with many active constituents that contribute to numerous beneficial functions, including immune regulation. These components collectively serve as a shield for the gut barrier, protecting against various threats such as biological, chemical, mechanical, and immunological threats. This comprehensive review delves into the active ingredients in milk, encompassing casein, α-lactalbumin, ß-lactoglobulin, lactoferrin, the milk fat globular membrane, lactose, transforming growth factor, and glycopeptides. The primary focus is to elucidate their impact on the integrity and function of the gut barrier. Furthermore, the implications of different processing methods of dairy products on the gut barrier protection are discussed. In conclusion, this study aimed to underscore the vital role of milk and dairy products in sustaining gut barrier health, potentially contributing to broader perspectives in nutritional sciences and public health.

Environmental endocrine disruptors and pregnane X receptor action: A review.

The pregnane X receptor (PXR) is a kind of orphan nuclear receptor activated by a series of ligands. Environmental endocrine disruptors (EEDs) are a wide class of molecules present in the environment that are suspected to have adverse effects on the endocrine system by interfering with the synthesis, transport, degradation, or action of endogenous hormones. Since EEDs may modulate human/rodent PXR, this review aims to summarize EEDs as PXR modulators, including agonists and antagonists. The modular structure of PXR is also described, interestingly, the pharmacology of PXR have been confirmed to vary among different species. Furthermore, PXR play a key role in the regulation of endocrine function. Endocrine disruption of EEDs via PXR and its related pathways are systematically summarized. In brief, this review may provide a way to understand the roles of EEDs in interaction with the nuclear receptors (such as PXR) and the related pathways.

Dietary regulation of peroxisome proliferator-activated receptors in metabolic syndrome.

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are a class of ligand-activated nuclear transcription factors, members of the type nuclear receptor superfamily, with three subtypes, namely PPARα, PPARß/δ, and PPARγ, which play a key role in the metabolic syndrome. In the past decades, a large number of studies have shown that natural products can act by regulating metabolic pathways mediated by PPARs. PURPOSE: This work summarizes the physiological importance and clinical significance of PPARs and reviews the experimental evidence that natural products mediate metabolic syndrome via PPARs. METHODS: This study reviews relevant literature on clinical trials, epidemiology, animals, and cell cultures published in NCBI PubMed, Scopus, Web of Science, Google Scholar, and other databases from 2001 to October 2022. Search keywords were "natural product" OR "botanical" OR "phytochemical" AND "PPAR" as well as free text words. RESULTS: The modulatory involvement of PPARs in the metabolic syndrome has been supported by prior research. It has been observed that many natural products can treat metabolic syndrome by altering PPARs. The majority of currently described natural compounds are mild PPAR-selective agonists with therapeutic effects that are equivalent to synthetic medicines but less harmful adverse effects. CONCLUSION: PPAR agonists can be combined with natural products to treat and prevent metabolic syndrome. Further human investigations are required because it is unknown how natural products cause harm and how they might have negative impacts.

In vitro and in silico assessment of endocrine disrupting effects of food contaminants through pregnane X receptor.

As a promiscuous xenobiotic receptor, pregnane X receptor (PXR) has been confirmed to participate in numerous physiological process. In addition to the conventional estrogen/androgen receptor, PXR also serves as an alternative target for environmental chemical contaminants. In this work, the PXR-mediated endocrine disrupting effects of typical food contaminants were explored. Firstly, the time-resolved fluorescence resonance energy transfer assays confirmed the PXR binding affinities of 2,2',4,4',5,5'-hexachlorobiphenyl, bis(2-ethylhexyl) phthalate, dibutyl phthalate, chlorpyrifos, bisphenol A, and zearalenone, with IC50 values ranging from 1.88 to 4284.00 nM. Then their PXR agonist activities were assessed by PXR-mediated CYP3A4 reporter gene assays. Subsequently, the regulation of gene expressions of PXR and its targets CYP3A4, UGT1A1, and MDR1 by these compounds was further investigated. Intriguingly, all the tested compounds interfered with these gene expressions, confirming their endocrine disrupting effects via PXR-mediated signaling. The compound-PXR-LBD binding interactions were explored by molecular docking and molecular dynamics simulations to unravel the structural basis of their PXR binding capacities. The weak intermolecular interactions are key players in stabilizing these compound-PXR-LBD complexes. During the simulation process, 2,2',4,4',5,5'-hexachlorobiphenyl remained stable while the other 5 compounds underwent relatively severe disturbances. In conclusion, these food contaminants might exhibit endocrine disrupting effects via PXR.