RESUMO
Microplastics (MPs) are widespread contaminants highly persistent in the environment and present in matrices to which humans are extensively exposed, including food and beverages. MP ingestion occurs in adults and children and is becoming an emerging public health issue. The gastrointestinal system is the most exposed to MP contamination, which can alter its physiology starting from changes in the microbiome. This study investigates by an omic approach the impact of a single intake of a mixture of polyethylene (PE) and polystyrene (PS) MPs on the ecology and metabolic activity of the colon microbiota of healthy volunteers, in an in vitro intestinal model. PE and PS MPs were pooled together in a homogeneous mix, digested with the INFOGEST system, and fermented with MICODE (multi-unit in vitro colon model) at loads that by literature correspond to the possible intake of food-derived MPs of a single meal. Results demonstrated that MPs induced an opportunistic bacteria overgrowth (Enterobacteriaceae, Desulfovibrio spp., Clostridium group I and Atopobium - Collinsella group) and a contextual reduction on abundances of all the beneficial taxa analyzed, with the sole exception of Lactobacillales. This microbiota shift was consistent with the changes recorded in the bacterial metabolic activity.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Glioblastoma (GB) is the most aggressive and prevalent glioma within the central nervous system. Despite considerable efforts, GB continues to exhibit a dismal 5-year survival rate (â¼6%). This is largely attributed to unfavorable prognosis and lack of viable treatment options. Therefore, novel therapies centered around plant-derived compounds emerge as a compelling avenue to enhance patient survival and well-being. The South African species, Plectranthus hadiensis Schweinf. (P. hadiensis), a member of the Lamiaceae family, has a history of use in traditional medicine for treating a range of diseases, including respiratory, digestive, and liver disorders. This species exhibits diverse biological activities, such as anti-inflammatory and antitumoral properties, likely attributed to its rich composition of naturally occurring diterpenes, like the abietane diterpene, 7α-acetoxy-6ß-hydroxyroyleanone (Roy). Roy has demonstrated promising antitumor effects in various cancer cell lines, making it a compelling candidate for further investigation into its mechanisms against GB. AIM OF THE STUDY: This study aims to investigate the antitumor activity and potential mechanism of Roy, a natural lead compound, in GB cells. MATERIAL AND METHODS: Roy was isolated from the acetonic extract of P. hadiensis and its antitumor mechanism was assessed in a panel of human GB cell lines (U87, A172, H4, U373, and U118) to mimic tumor heterogeneity. Briefly, the impact of Roy treatment on the metabolic activity of cells was evaluated by Alamar Blue® assay, while cell death, cell cycle regulation, mitochondrial membrane potential, and activated caspase-3 activity were evaluated by flow cytometry. Measurement of mRNA levels of target genes was performed by qPCR, while protein expression was assessed by Western blotting. Cell uptake and impact on mitochondrial morphology were evaluated by confocal microscopy. RESULTS: Roy induced G2/M cell cycle arrest, mitochondrial fragmentation, and apoptosis by inhibiting the expression of anti-apoptotic proteins and increasing the levels of activated caspase-3. The concentrations of Roy needed to achieve significant inhibitory outcomes were notably lower (6-9 fold) than those of temozolomide (TMZ), the standard first-line treatment, for achieving comparable effects. In addition, at low concentrations (16 µM), Roy affected the metabolic activity of tumor cells while having no significant impact on non-tumoral cells (microglia and astrocytes). CONCLUSION: Overall, Roy demonstrated a robust antitumor activity against GB cells offering a promising avenue for the development of novel chemotherapeutic approaches.