Showing papers by "John M. Pezzuto published in 2023"

Influence of grape consumption on the human microbiome

Abstract: Over the years, a substantial body of information has accumulated suggesting dietary consumption of grapes may have a positive influence on human health. Here, we investigate the potential of grapes to modulate the human microbiome. Microbiome composition as well as urinary and plasma metabolites were sequentially assessed in 29 healthy free-living male (age 24-55 years) and female subjects (age 29-53 years) following two-weeks of a restricted diet (Day 15), two-weeks of a restricted diet with grape consumption (equivalent to three servings per day) (Day 30), and four-weeks of restricted diet without grape consumption (Day 60). Based on alpha-diversity indices, grape consumption did not alter the overall composition of the microbial community, other than with the female subset based on the Chao index. Similarly, based on beta-diversity analyses, the diversity of species was not significantly altered at the three time points of the study. However, following 2 weeks of grape consumption, taxonomic abundance was altered (e.g., decreased Holdemania spp. and increased Streptococcus thermophiles), as were various enzyme levels and KEGG pathways. Further, taxonomic, enzyme and pathway shifts were observed 30 days following the termination of grape consumption, some of which returned to baseline and some of which suggest a delayed effect of grape consumption. Metabolomic analyses supported the functional significance of these alterations wherein, for example, 2'-deoxyribonic acid, glutaconic acid, and 3-hydroxyphenylacetic acid were elevated following grape consumption and returned to baseline following the washout period. Inter-individual variation was observed and exemplified by analysis of a subgroup of the study population showing unique patterns of taxonomic distribution over the study period. The biological ramifications of these dynamics remain to be defined. However, while it seems clear that grape consumption does not perturb the eubiotic state of the microbiome with normal, healthy human subjects, it is likely that shifts in the intricate interactive networks that result from grape consumption have physiological significance of relevance to grape action.

Anti-inflammatory Quinoline Alkaloids from the Roots of Waltheria indica.

Abstract: Sixteen new quinoline alkaloids (1a-7, 8a, 9, 10, 13-15, 17, and 21) and 10 known analogs (8b, 11, 12, 16, 18-20, and 22-24), along with three known cyclopeptide alkaloids (25-27), were isolated from the roots of Waltheria indica. The structures of the new compounds were elucidated by detailed NMR and circular dichroism with computational support and mass spectrometry data interpretation. Anti-inflammatory potential of isolates was evaluated based on inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-α)-induced nuclear factor kappa B (NF-κB) activity with cell culture models. In the absence of cell growth inhibition, compounds 6, 8a, 9-11, 13, 21, and 24 reduced TNF-α-induced NF-κB activity with IC50 values ranging from 7.1 to 12.1 μM, comparable to the positive control (BAY 11-7082, IC50 = 9.7 μM). Compounds 6, 8a, 8b, and 11 showed significant NO-inhibitory activity with IC50 values ranging from 11.0 to 12.8 μM, being more active than the positive control (l-NMMA, IC50 = 22.7 μM). Structure-activity relationships indicated that NO inhibitory activity was significantly affected by C-8 substitution. Inhibition of LPS-induced nitric oxide synthase (iNOS) by 8b [(5S)-waltherione M, IC50 11.7 ± 0.8 μM] correlated with inhibition of iNOS mRNA expression. The biological potential of W. indica metabolites supports the traditional use of this plant for the treatment of inflammatory-related disorders.