Browsing by Author "Thomford, Nicholas E."

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    Host and microbiome genome-wide association studies : current state and challenges
    (Frontiers Media, 2019) Awany, Denis; Allali, Imane; Dalvie, Shareefa; Hemmings, Sian M. J.; Mwaikono, Kilaza S.; Thomford, Nicholas E.; Gomez, Andres; Mulder, Nicola; Chimusa, Emile R.
    The involvement of the microbiome in health and disease is well established. Microbiome genome-wide association studies (mGWAS) are used to elucidate the interaction of host genetic variation with the microbiome. The emergence of this relatively new field has been facilitated by the advent of next generation sequencing technologies that enable the investigation of the complex interaction between host genetics and microbial communities. In this paper, we review recent studies investigating host–microbiome interactions using mGWAS. Additionally, we highlight the marked disparity in the sampling population of mGWAS carried out to date and draw attention to the critical need for inclusion of diverse populations.
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    Inhibition of CYP2B6 by medicinal plant extracts : implication for use of efavirenz and nevirapine-based highly active anti-retroviral therapy (HAART) in resource-limited settings
    (MDPI, 2016-02-16) Thomford, Nicholas E.; Awortwe, Charles; Dzobo, Kevin; Adu, Faustina; Chopera, Denis; Wonkam, Ambroise; Skelton, Michelle; Blackhurst, Dee; Dandara, Collet
    Highly active antiretroviral therapy (HAART) has greatly improved health parameters of HIV infected individuals. However, there are several challenges associated with the chronic nature of HAART administration. For populations in health transition, dual use of medicinal plant extracts and conventional medicine poses a significant challenge. There is need to evaluate interactions between commonly used medicinal plant extracts and antiretroviral drugs used against HIV/AIDS. Efavirenz (EFV) and nevirapine (NVP) are the major components of HAART both metabolized by CYP2B6, an enzyme that can potentially be inhibited or induced by compounds found in medicinal plant extracts. The purpose of this study was to evaluate the effects of extracts of selected commonly used medicinal plants on CYP2B6 enzyme activity. Recombinant human CYP2B6 was used to evaluate inhibition, allowing the assessment of herb-drug interactions (HDI) of medicinal plants Hyptis suaveolens, Myrothamnus flabellifolius, Launaea taraxacifolia, Boerhavia diffusa and Newbouldia laevis. The potential of these medicinal extracts to cause HDI was ranked accordingly for reversible inhibition and also classified as potential time-dependent inhibitor (TDI) candidates. The most potent inhibitor for CYP2B6 was Hyptis suaveolens extract (IC50 = 19.09 ± 1.16 µg/mL), followed by Myrothamnus flabellifolius extract (IC50 = 23.66 ± 4.86 µg/mL), Launaea taraxacifolia extract (IC50 = 33.87 ± 1.54 µg/mL), and Boerhavia diffusa extract (IC50 = 34.93 ± 1.06 µg/mL). Newbouldia laevis extract, however, exhibited weak inhibitory effects (IC50 = 100 ± 8.71 µg/mL) on CYP2B6. Launaea taraxacifolia exhibited a TDI (3.17) effect on CYP2B6 and showed a high concentration of known CYP450 inhibitory phenolic compounds, chlorogenic acid and caffeic acid. The implication for these observations is that drugs that are metabolized by CYP2B6 when co-administered with these herbal medicines and when adequate amounts of the extracts reach the liver, there is a high likelihood of standard doses affecting drug plasma concentrations which could lead to toxicity.