Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products.

In this study, we used an in vitro Caco-2 cell monolayer model to evaluate aqueous extracts of commercial-source goldenseal (Hydrastis canadensis) and milk thistle (Silybum marianum) capsule formulations, their marker phytochemicals (berberine and silibinin, respectively), as well as dillapiol, vinblastine, and the HIV protease inhibitor saquinavir for their ability to modulate CYP3A4 and ABCB1 expression after short-term exposure (48 h). Both upregulation and downregulation of CYP3A4 expression was observed with extracts of varying concentrations of the two natural health products (NHPs). CYP3A4 was highly responsive in our system, showing a strong dose-dependent modulation by the CYP3A4 inhibitor dillapiol (upregulation) and the milk thistle flavonolignan silibinin (downregulation).

In vitro evaluation of human cytochrome P450 and P-glycoprotein-mediated metabolism of some phytochemicals in extracts and formulations of African potato.

African potato (Hypoxis hemerocallidea, AP) is a traditional herbal medicine widely used as an immune booster and also for the treatment of various ailments such as urinary diseases, prostrate hypertrophy and cancer. Amongst the chemical components contained in AP, the norlignan glycoside, hypoxoside (HYP) is purported to be the most important phytochemical in terms of AP's medicinal value. Additional constituents in AP include the sterols, beta-sitosterol (BSS), stigmasterol (STG), and the stanol, stigmastanol (STN).

Novel chemistry of invasive exotic plants.

Of the many exotic plants that have become naturalized in North America, only a small proportion are pests capable of invading and dominating intact natural communities. In the present study, we tested the hypothesis that the most invasive plants are phytochemically unique in their new habitats. A comparison of exotic plant species that are highly invasive in North America with exotics that are widespread, but non-invasive revealed that the invasive plants were more likely to have potent secondary compounds that have not been reported from North American native plants.

Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients.

Gene expression profiles were examined in freshly isolated peripheral blood mononuclear cells (PBMC) from two independent cohorts (training and test sets) of glucocorticoid (GC)-sensitive (n = 64) and GC-resistant (n = 42) asthma patients in search of genes that accurately predict responders and nonresponders to inhaled corticosteroids. A total of 11,812 genes were examined with high-density oligonucleotide microarrays in both resting PBMC (106 patients) and cells treated in vitro with IL-1beta and TNF-alpha combined (88 patients), with or without GC. A total of 5,011 genes were expressed at significant levels in the PBMC, and 1,334 of those were notably up-regulated or down-regulated by IL-1beta/TNF-alpha treatment.

Natural health products and drug disposition.

Botanicals such as herbal products (HPs) and nutraceuticals (NCs) are often regarded as low risk because of their long history of human use. Anecdotal and literature reports of adverse drug events (ADEs) and clinical studies with HPs are increasing, but many of the reports are incomplete and contradictory. These reports need to identify confounding factors and explain contradictory findings if they are to help health care professionals or patients understand what risks are involved.

Ethnomedicinal uses of Momordicacharantia (Cucurbitaceae) in Togo and relation to its phytochemistry and biological activity.

Investigation of the traditional uses of Momordica charantia (Cucurbitaceae) in Togo (West Africa) showed that it is one of the most important local medicinal plants both for ritual and ethnomedical practices. There was a high degree of consensus (>50%) for use in the treatment of gastrointestinal and viral disease among 47 groups of village informants in the general population, while 19 traditional healers reported a larger and broader set of uses. The use by informants in Gaur and Kwa language groups was not significantly different.

Genetic approaches to assessing evidence for a T helper type 1 cytokine defect in adult asthma.

Recent evidence suggests that deficiency in the Th1 cytokine pathway may underlie the susceptibility to allergic asthma. This study examined whether (1) single-nucleotide polymorphisms exist in the promoter region of the two interleukin (IL)-12 subunit genes in patients with asthma; (2) messenger RNA and protein expressions of signal transducers and activators of transcription, IL-12, IFN-gamma, and their receptors are altered in asthma; and (3) linkage to genes in the Th1 pathway is present in families with asthma in Iceland. The promoter regions of the IL-12 subunit genes were sequenced in 94 patients with asthma and 94 control subjects without asthma.

Phytochemistry of wild populations of Panax quinquefolius L. (North American ginseng).

A survey of the phytochemistry of Panax quinquefolius L. (North American ginseng) collected from wild populations in Ontario, Quebec, Maine, Vermont, and Wisconsin was undertaken. Reverse-phase HPLC was used to determine the natural variation of levels of ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd and their total in leaf, stem, and root of authentic wild-grown material.

A major susceptibility gene for asthma maps to chromosome 14q24.

Asthma is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. Numerous loci and candidate genes have been reported to show linkage and association to asthma and atopy. Although some studies reporting these observations are compelling, no gene has been mapped that confers a sufficiently high risk of asthma to meet the stringent criteria for genomewide significance.

How do insect herbivores cope with the extreme oxidative stress of phototoxic host plants?

Plants of the Asteraceae and Hypericaceae possess secondary compounds that induce photooxidation in insect herbivores that consume them. One of the well-established modes of action of these substances is peroxidation of membrane lipids. Some herbivores counteract these defences by avoidance of light and tissues rich in phototoxins or the ability to detoxify these secondary substances.