An untargeted metabolomics approach applied to the study of the bioavailability and metabolism of three different bioactive plant extracts in human blood samples.

Advances in the understanding of bioavailability and metabolism of bioactive compounds have been achieved primarily through targeted or semi-targeted metabolomics approaches using the hypothesis of potential metabolized compounds. The recent development of untargeted metabolomics approaches can present great advantages in this field, such as in the discovery of new metabolized compounds or to study the metabolism of compounds from multiple matrices simultaneously. Thus, this study proposes the use of an untargeted metabolomics strategy based on HPLC-ESI-QTOF-MS for the study of bioavailability and metabolism of bioactive compounds from different vegetal sources. Specifically, this study has been applied to plasma samples collected in an acute human intervention study using three matrices (Hibiscus sabdariffa, Silybum marianum and Theobroma cacao). This approach allowed the selection of those significant variables associated with exogenous metabolites derived from the consumption of bioactive compounds for their subsequent identification. As a result, 14, 25 and 3 potential metabolites associated with supplement intake were significantly detected in the plasma samples from volunteers who ingested the H. sabdariffa (HS), S. marianum (SM) and T. cacao (TC) extracts. Furthermore, Tmax values have been computed for each detected compound. The results highlight the potential of untargeted metabolomics for rapid and comprehensive analysis when working with a wide range of exogenous metabolites from different plant sources in biological samples.

Integration of multi-omics analysis reveals metabolic alterations of B lymphocytes in systemic lupus erythematosus.

OBJECTIVE: To link changes in the B-cell transcriptome from systemic lupus erythematosus (SLE) patients with those in their macroenvironment, including cellular and fluidic components. METHODS: Analysis was performed on 363 patients and 508 controls, encompassing transcriptomics, metabolomics, and clinical data. B-cell and whole-blood transcriptomes were analysed using DESeq and GSEA. Plasma and urine metabolomics peak changes were quantified and annotated using Ceu Mass Mediator database. Common sources of variation were identified using MOFA integration analysis. RESULTS: Cellular macroenvironment was enriched in cytokines, stress responses, lipidic synthesis/mobility pathways and nucleotide degradation. B cells shared these pathways, except nucleotide degradation diverted to nucleotide salvage pathway, and distinct glycosylation, LPA receptors and Schlafen proteins. CONCLUSIONS: B cells showed metabolic changes shared with their macroenvironment and unique changes directly or indirectly induced by IFN-α signalling. This study underscores the importance of understanding the interplay between B cells and their macroenvironment in SLE pathology.

High potential extracts from cocoa byproducts through sonotrode optimal extraction and a comprehensive characterization.

Cocoa pod husk (CPH) and cocoa bean shell (CBS) are by-products obtained during pre-processing and processing of cocoa beans. Several bioactive compounds have been identified in these by-products that can be used for commercial applications as a way to promote the circular economy. Therefore, the objective of this paper was to recover bioactive compounds from CPH and CBS by sonoextraction process, to determine the type, content, and antioxidant activity in optimized extracts. To achieve our purpose, an optimization strategy using Box-Behnken Design coupled response surface methodology (MRS) was applied. The extraction conditions were optimized. The results obtained for CBS were: TPC (193 mg GAE/g), TEAC (1.02 mmol TE/g), FRAP (1.02 mmol FeSO4/g) and ORAC (2.6 mmol TE/g), while for CPH, the reported values were: TPC (48 mg GAE/g), TEAC (0.30 mmol TE/g), FRAP (0.35 mmol FeSO4/g) and ORAC (0.43 mmol TE/g) under the optimized conditions: Time (XA): 15 min, Amplitude (XB): 80 %, Ethanol (XC): 50 %. The LC-ESI-qTOF-MS analysis results allowed the identification of 79 compounds, of which 39 represent the CBS extract, while 40 compounds were identified in CPH extract. To conclude, sonotrode based extraction could be considered as an efficient and fast alternative for the recovery of bioactive substances from CBS and CPH.

Bioactive Compounds and Potential Health Benefits through Cosmetic Applications of Cherry Stem Extract.

Cherry stems, prized in traditional medicine for their potent antioxidant and anti-inflammatory properties, derive their efficacy from abundant polyphenols and anthocyanins. This makes them an ideal option for addressing skin aging and diseases. This study aimed to assess the antioxidant and anti-inflammatory effects of cherry stem extract for potential skincare use. To this end, the extract was first comprehensively characterized by HPLC-ESI-qTOF-MS. The extract's total phenolic content (TPC), antioxidant capacity, radical scavenging efficiency, and its ability to inhibit enzymes related to skin aging were determined. A total of 146 compounds were annotated in the cherry stem extract. The extract effectively fought against NO· and HOCl radicals with IC50 values of 2.32 and 5.4 mg/L. Additionally, it inhibited HYALase, collagenase, and XOD enzymes with IC50 values of 7.39, 111.92, and 10 mg/L, respectively. Based on the promising results that were obtained, the extract was subsequently gently integrated into a cosmetic gel at different concentrations and subjected to further stability evaluations. The accelerated stability was assessed through temperature ramping, heating-cooling cycles, and centrifugation, while the long-term stability was evaluated by storing the formulations under light and dark conditions for three months. The gel formulation enriched with cherry stem extract exhibited good stability and compatibility for topical application. Cherry stem extract may be a valuable ingredient for creating beneficial skincare cosmeceuticals.

Metabolite Profiling of Colvillea racemosa via UPLC-ESI-QTOF-MS Analysis in Correlation to the In Vitro Antioxidant and Cytotoxic Potential against A549 Non-Small Cell Lung Cancer Cell Line.

In this study, flower and leaf extracts of Colvillea racemosa were considered a source of bioactive compounds. In this context, the objective of the study focused on investigating the anticancer potential as well as the phytochemical composition of both extracts. The extracts were analyzed by UPLC-ESI-QTOF-MS, and the bioactivity was tested using in vitro antioxidant assays (FRAP, DPPH, and ABTS) in addition to cytotoxic assays on non-small cell lung cancer cell line (A549). Our results clearly indicated the potent radical scavenging capacity of both extracts. Importantly, the flower extract exhibited a greater antioxidant capacity than the leaf extract. In terms of cytotoxic activity, leaf and flower extracts significantly inhibited cell viability with IC50 values of 17.0 and 17.2 µg/mL, respectively. The phytochemical characterization enabled the putative annotation of 42 metabolites, such as saccharides, phenolic acids, flavonoids, amino acids, and fatty acids. Among them, the flavonoid C-glycosides stand out due to their high relative abundance and previous reports on their anticancer bioactivity. For a better understanding of the bioactive mechanisms, four flavonoids (vitexin, kaempferol-3-O-rutinoside, luteolin, and isoorientin) were selected for molecular docking on hallmark protein targets in lung cancer as represented by γ-PI3K, EGFR, and CDK2 through in-silico studies. In these models, kaempferol-3-O-rutinoside and vitexin had the highest binding scores on γ-PI3K and CDK2, followed by isoorientin, so they could be highly responsible for the bioactive properties of C. racemosa extracts.

Evaluation of Bioactive Effects of Five Plant Extracts with Different Phenolic Compositions against Different Therapeutic Targets.

Plant extracts rich in phenolic compounds have been reported to exert different bioactive properties. Despite the fact that there are plant extracts with completely different phenolic compositions, many of them have been reported to have similar beneficial properties. Thus, the structure-bioactivity relationship mechanisms are not yet known in detail for specific classes of phenolic compounds. In this context, this work aims to demonstrate the relationship of extracts with different phenolic compositions versus different bioactive targets. For this purpose, five plant matrices (Theobroma cacao, Hibiscus sabdariffa, Silybum marianum, Lippia citriodora, and Olea europaea) were selected to cover different phenolic compositions, which were confirmed by the phytochemical characterization analysis performed by HPLC-ESI-qTOF-MS. The bioactive targets evaluated were the antioxidant potential, the free radical scavenging potential, and the inhibitory capacity of different enzymes involved in inflammatory processes, skin aging, and neuroprotection. The results showed that despite the different phenolic compositions of the five matrices, they all showed a bioactive positive effect in most of the evaluated assays. In particular, matrices with very different phenolic contents, such as T. cacao and S. marianum, exerted a similar inhibitory power in enzymes involved in inflammatory processes and skin aging. It should also be noted that H. sabdariffa and T. cacao extracts had a low phenolic content but nevertheless stood out for their bioactive antioxidant and anti-radical capacity. Hence, this research highlights the shared bioactive properties among phenolic compounds found in diverse matrices. The abundance of different phenolic compound families highlights their elevated bioactivity against diverse biological targets.

Novel insights into enzymes inhibitory responses and metabolomic profile of supercritical fluid extract from chestnut shells upon intestinal permeability.

The health benefits of chestnut (Castanea sativa) shells (CSs) have been ascribed to phytochemicals, mainly phenolic compounds. Nevertheless, an exhaustive assessment of their intestinal absorption is vital considering a possible nutraceutical application. This study evaluated the bioactivity of CSs extract prepared by Supercritical Fluid Extraction and untargeted metabolomic profile upon in-vitro intestinal permeation across a Caco-2/HT29-MTX co-culture model. The results demonstrated the neuroprotective, hypoglycemic, and hypolipidemic properties of CSs extract by inhibition of acetylcholinesterase, α-amylase, and lipase activities. The untargeted metabolic profiling by LC-ESI-LTQ-Orbitrap-MS unveiled almost 60 % of lipids and 30 % of phenolic compounds, with 29 metabolic pathways indicated by enrichment analysis. Among phenolics, mostly phenolic acids, flavonoids, and coumarins permeated the intestinal barrier with most metabolites arising from phase I reactions (reduction, hydrolysis, and hydrogenation) and a minor fraction from phase II reactions (methylation). The permeation rates enhanced in the following order: ellagic acid < o-coumaric acid < p-coumaric acid < ferulaldehyde ≤ hydroxyferulic acid ≤ dihydroferulic acid < ferulic acid < trans-caffeic acid < trans-cinnamic acid < dihydrocaffeic acid, with better outcomes for 1000 µg/mL of extract concentration and after 4 h of permeation. Taken together, these findings sustained a considerable in-vitro intestinal absorption of phenolic compounds from CSs extract, enabling them to reach target sites and exert their biological effects.

The Antioxidant Properties of Salvia verbenaca Extract Contribute to Its Intestinal Antiinflammatory Effects in Experimental Colitis in Rats.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammation with unpredictable symptom fluctuations. While there is no effective cure for IBD, various treatments aim to manage symptoms and improve the quality of life for affected individuals. In recent years, there has been growing interest in the potential benefits of certain natural plants and herbs in the management of IBD. In this regard, this study aimed to evaluate the immunomodulatory and anti-inflammatory effects of a well-characterized extract of Salvia verbenaca (S. verbenaca) in an experimental model of colitis in rats. Interestingly, the daily administration of S. verbenaca (10 and 25 mg/kg) effectively alleviated colitis symptoms, as evidenced by reduced weight/length ratio and colonic damage. Moreover, it reduced oxidative stress markers (MPO and GSH), decreased pro-inflammatory cytokine expression (Il-6, Il-12a, Il-1ß, Il-23, Icam-1, Mcp-1, Cinc-1), and preserved the integrity of the intestinal barrier (Villin, Muc-2, Muc-3). These effects suggest S. verbenaca extract could represent a potential complementary candidate to treat gastrointestinal disorders. Its beneficial actions can be related to its antioxidant properties as well as the downregulation of the immune response, which can result in the improvement in the intestine epithelial barrier.