Chronic Kidney Disease (CKD) is a debilitating disease associated with several secondary complications that increase comorbidity and mortality. In patients with CKD, there is a significant qualitative and quantitative alteration in the gut microbiota, which, consequently, also leads to reduced production of beneficial bacterial metabolites, such as short-chain fatty acids. Evidence supports the beneficial effects of short-chain fatty acids in modulating inflammation and oxidative stress, which are implicated in CKD pathogenesis and progression. Therefore, this review will provide an overview of the current knowledge, based on pre-clinical and clinical evidence, on the effect of SCFAs on CKD-associated inflammation and oxidative stress.
5-Fluorouracil (5-FU) is a pyrimidine analogue used as an antineoplastic agent to treat multiple solid tumors. Despite its use and efficacy, it also has important side effects in healthy cells, including skin reactions, related to its pro-oxidant and pro-inflammatory potential. Although there are numerous remedies for chemotherapy-induced skin reactions, the efficacy of these treatments remains limited. In this study we focused on the effects of pomegranate (Punica granatum L.) juice extract (PPJE) on the oxidative and inflammatory state in 5-FU-treated human skin keratinocytes (HaCaT). The obtained results showed that PPJE significantly inhibited reactive oxygen species release and increased the cellular antioxidant response, as indicated by the increased expression of cytoprotective enzymes, such as heme oxygenase-1 and NAD(P)H dehydrogenase [quinone] 1. In these experimental conditions, PPJE also inhibited nitrotyrosine formation and 5-FU-induced inflammatory response, as indicated by the reduced cytokine level release. Moreover, PPJE inhibited nuclear translocation of p65-NF-κB, a key factor regulating the inflammatory response. In 5-FU-treated HaCaT cells PPJE also inhibited apoptosis and promoted wound repair. These results suggest a potential use of PPJE as an adjuvant in the treatment of the oxidative and inflammatory state that characterizes chemotherapy-induced skin side effects.
The phytochemical investigation of Ulmus minor subsp. minor samaras EtOAc and n-BuOH extracts is reported in this work for the first time, resulting in the isolation and characterization of twenty compounds (1-20) including one new flavan-3-ol (1), one new trihydroxy fatty acid (2), and two glycosylated flavonoids (6-7) whose NMR data are not available in the literature. Structure elucidation of the isolated compounds was obtained by 1D and 2D NMR and HRESIMS data. Prior to further pharmacological investigations, the extracts (100-6.25 µg/mL) and compounds 1-12 (50-5 µM) were tested for their influence on viability of a murine macrophage cell line (J774A.1). Subsequently, extracts and compounds that did not impede viability were studied for their inhibitory effect on some mediators of inflammation in J774A.1 cells stimulated with lipopolysaccharide of Escherichia coli (LPS). The NO release and the expression of iNOS and COX-2 were then evaluated and both extracts (50-6.25 µg/mL) and compounds (20-5 µM) significantly inhibited NO release as well as iNOS and COX-2 expression in macrophages. These data highlight the anti-inflammatory properties of several isolated compounds from U. minor samaras supporting its possible alimentary use.
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