Many bioactive plant compounds, known as phytochemicals, have the potential to improve health. Unfortunately, the bioavailability and bioactivity of phytochemicals such as polyphenolic flavonoids are reduced due to conjugation with sugar moieties. Here, we combine acid hydrolysis and tailored fermentation by lactic acid bacteria (Lactiplantibacillus plantarum) to convert the biologically less active flavonoid glycosides hesperidin and naringin into the more active aglycones hesperetin and naringenin. Using a comprehensive approach, we identify the most effective hydrolysis and fermentation conditions to increase the concentration of the aglycones in citrus extracts. The higher cellular transport and bioactivity of the biotransformed citrus extract are also demonstrated in vitro and in vivo. Superior antioxidant, anti-inflammatory and cell migration activities in vitro, as well as intestinal barrier protecting and antioxidant activities in Drosophila melanogaster are identified. In conclusion, the presented biotransformation approach improves the bioactivity of flavonoids, clearly traced back to the increase in aglycone content.

Inhibition of intestinal glucose resorption can serve as an effective strategy for the prevention of an increase in blood glucose levels. We have recently shown that various extracts prepared from guava (Psidium guajava) inhibit sodium-dependent glucose cotransporter 1 (SGLT1)- and glucose transporter 2 (GLUT2)-mediated glucose transport in vitro (Caco-2 cells) and in vivo (C57BL/6N mice). However, the efficacy in humans remains to be confirmed. For this purpose, we conducted a parallelized, randomized clinical study with young healthy adults. Thirty-one volunteers performed an oral glucose tolerance test (OGTT) in which the control group received a glucose solution and the intervention group received a glucose solution containing a guava fruit extract prepared by supercritical CO₂ extraction. The exact same extract was used for our previous in vitro and in vivo experiments. Blood samples were collected prior to and up to two hours after glucose consumption to quantitate blood glucose and insulin levels. Our results show that, in comparison to the control group, consumption of guava fruit extract resulted in a significantly reduced increase in postprandial glucose response over the basal fasting plasma glucose levels after 30 min (Δ control 2.60 ± 1.09 mmol/L versus Δ intervention 1.96 ± 0.96 mmol/L; p = 0.039) and 90 min (Δ control 0.44 ± 0.74 mmol/L versus Δ intervention −0.18 ± 0.88 mmol/L; p = 0.023). In addition, we observed a slightly reduced, but non-significant insulin secretion (Δ control 353.82 ± 183.31 pmol/L versus Δ intervention 288.43 ± 126.19 pmol/L, p = 0.302). Interestingly, storage time and repeated freeze-thawing operations appeared to negatively influence the efficacy of the applied extract. Several analytical methods (HPLC-MS, GC-MS, and NMR) were applied to identify putative bioactive compounds in the CO₂ extract used. We could assign several substances at relevant concentrations including kojic acid (0.33 mg/mL) and 5-hydroxymethylfurfural (2.76 mg/mL). Taken together, this clinical trial and previous in vitro and in vivo experiments confirm the efficacy of our guava fruit extract in inhibiting intestinal glucose resorption, possibly in combination with reduced insulin secretion. Based on these findings, the development of food supplements or functional foods containing this extract appears promising for patients with diabetes and for the prevention of insulin resistance. Trial registration: 415-E/2319/15-2018 (Ethics Commissions of Salzburg).

Intestinal absorption is intrinsically low for lipophilic micronutrients and phytochemicals. Plant extracts acting as bioavailability enhancers can complement for this deficiency by modulation of both, physicochemical and biochemical parameters, in the absorption process. However, these interactions often are limited to specific conditions and the mechanisms and potential synergisms are poorly understood. In this work, we used a human intestinal cell line to characterize the impact of extracts from C. longa (curcuma), Z. officinale (ginger) and P.nigrum (black pepper) on uptake and transport rates of the xanthophylls lutein and zeaxanthin as well as soy isoflavones measured by HPLC-DAD. We found a significant increase in the uptake of lutein in the presence of curcuma extract and enhanced isoflavone transport rates mediated by curcuma and ginger extracts. Combinations of the plant extracts did not lead to any additional increase in uptake or transport rates. By investigation of mixed micelle incorporation efficiency, we could dismiss changes in bioaccessibility as a potential enhancing mechanism in our experimental setup. We further conducted a rhodamine 123 efflux assay and discovered inhibition of P-glycoproteins by the ginger and black pepper extracts, highlighting a plausible route of action leading to increased isoflavone bioavailability.

The rise of multidrug-resistant microorganisms primarily driven by the misuse and overprescription of antibiotics, is recognized as one of the top ten global health challenges. The identification of novel antimicrobial agents for the development of new drugs has been challenging and natural plant-based bioactive compounds may represent as alternative therapeutic options. Although the antibacterial properties of Allium ursinum (wild garlic) are well documented, no in vivo studies utilizing Caenorhabditis elegans to screen phytochemicals with antimicrobial activity have been conducted. This study aimed to investigate the antimicrobial effects of local wild garlic on C. elegans infected with Pseudomonas aeruginosa. Antimicrobial activity was evaluated through comprehensive analyses of worm morphology, reproductive capacity, and overall fitness. Additionally, the molecular mechanisms underlying these effects were examined at the mRNA and protein levels. Pretreatment of nematodes with wild garlic extract prior to P. aeruginosa infection led to a marked increase in worm length and a significant increase in the number of progeny. Additionally, co-incubation with the extract enhanced the fitness of the worms. Notably, wild garlic treatment significantly changed the expression of key genes associated with bacterial defense, immune responses, and oxidative stress in nematodes infected with P. aeruginosa, as determined by gene expression analyses and fluorescence microscopy. In conclusion, wild garlic exerted beneficial effects on worm size, progeny number, fitness and regulated the expression of key genes in the model organism C. elegans, demonstrating its potential as a natural alternative to synthetic antibiotics.

The restriction of antimicrobial growth promoters in livestock production has intensified the search for nutritional strategies that support intestinal health while modulating inflammatory processes. Chronic or dysregulated inflammation can impair gut function and animal performance, highlighting the need for functional feed additives. Brown macroalgae are rich in bioactive compounds with immunomodulatory properties, though their mechanisms remain incompletely understood. In this study, the anti-inflammatory and barrier-protective effects of aqueous extracts from Ascophyllum nodosum (AN) and Fucus vesiculosus (FV) were investigated using complementary in vitro and in vivo models. Extracts were prepared by aqueous solid–liquid extraction and tested in lipopolysaccharide (LPS)-stimulated RAW264.7 and THP-1 macrophages, HEK-Blue TLR4 reporter cells, and Drosophila melanogaster models of intestinal inflammation and infection. Both extracts significantly reduced LPS-induced nitric oxide production in RAW264.7 macrophages in a concentration-dependent manner. In THP-1 macrophages, AN and FV attenuated secretion of inflammatory mediators, including TNF-α, IL-6, IL-33, CXCL9, CXCL10, CXCL11, and CCL7. Reporter assays demonstrated selective inhibition of TLR4-dependent NF-κB activation. In Drosophila melanogaster, supplementation reduced intestinal barrier disruption, mortality, and infection-induced immune activation. Overall, AN and FV attenuate inflammatory signaling and protect intestinal integrity via TLR4-dependent NF-κB inhibition, supporting their potential as functional feed additives to enhance gut health and resilience in livestock.