Search Results (44)

Plant-derived compounds exhibit well-documented osteogenic and anti-resorptive activities; however, their translation into consistent skeletal benefits remains limited. This review proposes a transformation-state-dependent framework in which the efficacy of plant-based interventions is interpreted through the exposure architectures they generate rather than solely through intrinsic molecular activity. By integrating plant matrix organization, gastrointestinal processing, microbial biotransformation, and formulation-driven pharmacokinetics with the temporal dynamics of bone remodeling, the review addresses a critical gap in the current literature, which largely evaluates phytochemicals independent of their delivery context. Across a continuum ranging from intact plant matrices to isolated compounds and advanced delivery systems, distinct pharmacokinetic regimes emerge, characterized by differences in release kinetics, metabolic transformation, systemic persistence, and target-site exposure. Representative interventions showing promising pharmacokinetic and skeletal findings include curcumin phytosome systems, resveratrol nanoformulations, icariin-loaded delivery platforms, and matrix-associated polyphenol systems capable of promoting sustained or metabolite-mediated exposure. Evidence indicates that sustained, metabolite-mediated exposure profiles are more compatible with the prolonged, cumulative nature of bone remodeling, whereas transient exposure often limits efficacy despite mechanistic activity. Formulation strategies, including phospholipid complexes, bioenhancers, and nano- or vesicle-based systems, can partially overcome these limitations by modulating exposure behavior. By reframing plant-based interventions as dynamic exposure systems, this framework provides a unifying basis for interpreting variability across studies and offers a rational foundation for designing strategies that align pharmacokinetic behavior with skeletal biology, thereby improving translational potential. Full article

Tea polyphenols (TPs), the primary bioactive components derived from tea, play an important role in maintaining gut function and metabolic homeostasis. Emerging evidence indicates that the regulatory functions of TP within the intestine are intricately linked to their interactions with the gut microbiota. Serotonin (5-hydroxytryptamine, 5-HT), a key signaling molecule in the gastrointestinal tract, has been implicated in preserving intestinal function and metabolic health. Notably, the modulation of gut microbiota by TPs, the microbial biotransformation of TPs into bioactive metabolites, and the potential regulation on intestinal 5-HT homeostasis may collectively constitute an interconnected axis relevant to gut health and metabolic balance. However, direct experimental evidence linking these components into a unified mechanistic pathway remains limited, and the molecular basis of this putative TP–microbiota–5-HT axis requires further validation. This review systematically summarizes and discusses the regulatory effects of TPs on gut microbiota, and the microbial biotransformation of TPs into metabolites, as well as the microbial modulation of intestinal 5-HT and the roles of 5-HT and its receptors in intestinal function and homeostasis, with a particular focus on critically evaluating the extent to which current data support the proposed interactions among TPs, gut microbiota, and 5-HT in metabolic disorders. A deeper understanding of this tripartite interaction may ultimately inform the development of TP-based dietary approaches targeting gut microbiota–5-HT interactions in gut function and metabolic health, although such translational applications remain speculative in the absence of robust causal evidence. Full article

Zearalenone (ZEN) is an estrogenic mycotoxin produced by Fusarium spp. and commonly found in cereals and feed materials. This study evaluated the ability of Metschnikowia pulcherrima KKP 1368 biomass to reduce extractable ZEN under controlled buffered pH conditions (pH 3.50 and 7.00) selected as simplified conditions relevant to the porcine gastrointestinal environment. ZEN was quantified by LC-MS/MS, whereas LC-MS-QTOF was used as a qualitative/semi-quantitative screening approach for tentatively assigned transformation-related features. In the presence of yeast biomass, extractable ZEN was already lower than in the corresponding controls at the first sampling point, indicating a rapid biomass-associated effect. After 12 h, reductions relative to the corresponding controls reached 63.0% at pH 3.50 (p < 0.0001) and 51.6% at pH 7.00 (p = 0.0001). ZEN remained stable in control samples, and the strain remained viable under both pH conditions throughout incubation. LC-MS-QTOF detected several tentatively assigned features consistent with zearalanone, zearalenone-14-glucuronide, and zearalenol O-glucoside; these assignments require confirmation with authentic standards. Overall, M. pulcherrima KKP 1368 reduced extractable ZEN in a simplified buffered in vitro system, probably through rapid adsorption/reduced extractability and possible biotransformation. Further studies using biomass fractions or inactivated biomass, mass-balance experiments, authentic standards, and toxicological assays are needed to clarify the relative contribution of adsorption and transformation and to assess the practical relevance of this approach. Full article

In response to the plastic pollution crisis, bioplastics emerged as a sustainable alternative. However, low degradation rate and abiotic decomposition generate micro- and nanoplastics. These particles enter the food chain, establishing oral intake as a key route of human exposure. This review gathered studies on the biotransformation of bioplastics in the gastrointestinal tract and on their toxicity in human cells and murine models. Most studies focused on polylactic acid particles due to widespread use in food packaging. Under simulated gastrointestinal conditions in vitro, particles were modulated, resulting in cavity and pore formation, fragmentation, lipase competition, protein corona formation, and alterations in the gut microbiota (including Selenomonadaceae, Bifidobacterium, and Prevotellaceae). Also, particle breakdown increases surface area, enhancing interactions with biomolecules and causing higher in vitro and in vivo toxicity. Indeed, pro-inflammatory cytokine secretion, oxidative stress induction, and redox imbalance were found in both models. In mice, alterations in gut microbiota involving Bacillales indirectly mediated hepatotoxicity, leading to uric acid and triglyceride accumulation. Furthermore, microbiota adaptation over time was suggested with an increase in microorganisms and the potential conversion of L-lactic into harmful D-lactic acid. Despite limited studies, this review highlighted that ingested bioplastic-derived micro- and nanoplastics can lead to toxic effects. Full article

Background: In this study, we aimed to compare metabolomic profiles, biodistribution, and detoxification patterns of the novel SN-38 derivative NMe with irinotecan (IR), and to identify NMe-specific metabolites to evaluate its preclinical pharmacokinetic advantages. Methods: In vivo ADME studies were conducted for NMe, a 9-aminomethyl SN-38 derivative, and IR following a single intraperitoneal dose of 40 mg/kg in mice. Additionally, ADMET properties were predicted using ADMETlab and SwissADME tools for comparison. Levels of NMe and irinotecan absorbed into plasma, distributed to tissues, and metabolized were monitored in liver, lung, spleen, kidney, and stool samples at 15, 30, and 60 min post-administration. Tissue extracts were analysed using high-performance liquid chromatography (HPLC), liquid chromatography–electrospray ionization quadrupole time-of-flight-tandem mass spectrometry (LC-ESI-QTOF-MS), and nuclear magnetic resonance (NMR) techniques after lyophilization and reconstitution. We compared the metabolomic profiles of irinotecan and NMe. Results: We identified and confirmed NMe-specific metabolites, including 9-CH₂-S-cysteine conjugate, 9-CH₂OH, and NMe-formyl. Notably, novel irinotecan metabolites (IR-OH and IR-ΔE) were detected in small amounts in kidney samples. In some cases, two literature-known photodegradation products of irinotecan were present. NMe was found to quickly metabolize with different distribution to tissues, significantly greater to kidney and liver. Two SN-38 glucuronides, SN-38G(α) and SN-38G(β), were detected corresponding to α- and β-anomers. Where it was possible, NMe, IR and SN-38 were quantified using external calibration curves. In IR group, controlled and prolonged release of SN-38 was confirmed in all samples, yet SN-38G was observed in minority only in plasma, kidney, or lungs. In NMe groups, great relative amounts of SN-38 and SN-38G were detected. Greater content of SN-38G in NMe group than in irinotecan is expected to contribute to modulation and alleviation of some side effects in irinotecan-involved therapies, such as gastrointestinal toxicities (GIT). Conclusions: NMe shows a distinct metabolic profile characterized by rapid biotransformation, higher systemic glucuronidation of SN-38, and formation of unique metabolites, suggesting a potentially wider therapeutic window and reduced toxicity compared with IR. Full article

Background: Pometia pinnata (matoa) peel powder attenuates high-fat diet-induced adiposity and hepatic lipid accumulation in rats, but the responsible compounds remain unclear. This study aimed to identify the bioactive compounds that may contribute to this phenotype, with an emphasis on pancreatic lipase inhibition as a candidate mechanism. Methods: Rats received high-fat diets containing matoa peel powder, or its water- or ethanol extraction residue. Visceral fat accumulation, hepatic lipid deposition, and serum lipid profiles were evaluated. An ethanol extract was fractionated by activity-guided column chromatography based on pancreatic lipase-inhibitory activity, and structures were identified by nuclear magnetic resonance analysis. Static in vitro gastrointestinal digestion was performed to assess inhibition of fatty acid release by the extract or isolated compounds. Results: The visceral adiposity- and hepatic lipid-modulating effects observed with matoa peel powder were retained in the water extraction residue but not in the ethanol extraction residue, suggesting removal of bioactive constituents by ethanol extraction. The ethanol extract inhibited pancreatic lipase (IC₅₀ = 740 µg/mL). Two active compounds—hederagenin saponin and protocatechuic acid—were isolated, and both inhibited pancreatic lipase (IC₅₀ = 149 µmol/L and 404 µmol/L, respectively). Under simulated digestion in vitro, the ethanol extract and protocatechuic acid reduced free fatty acid release, whereas hederagenin saponin did not. Conclusions: Matoa peel powder contains ethanol-soluble constituents, including pancreatic lipase-inhibitory compounds that may contribute to the modulation of adiposity and hepatic lipid metabolism in high-fat-diet-fed rats. The attenuation of individual-compound activity under simulated digestion is consistent with matrix- and intestinal milieu-dependent effects, and supports a multi-component mechanism involving saponins, phenolics (protocatechuic acid), and their intestinal biotransformation products. Full article

The growing interest in sustainable food systems has spurred research into the valorisation of agro-industrial by-products as sources of bioactive compounds. This review provides a comprehensive overview of the phytochemical composition, bioactivity, biotransformation, and potential nutraceutical applications of by-products from chestnut (Castanea sativa Mill.) and grape (Vitis vinifera L.). Recent studies identify matrices such as chestnut leaves, shells, and burs, as well as grape pomace, skins, seeds, stems, and vine shoots, as rich in phenolic compounds, dietary fibres, vitamins, and minor bioactives, with antioxidant, anti-inflammatory, and antimicrobial properties. Emerging evidence highlights the importance of gastrointestinal digestion and microbial biotransformation in modulating the bioavailability and biological efficacy of phenolic compounds, particularly fibre-bound phenolics. The review further discusses state-of-the-art analytical approaches for chemical characterisation, including chromatographic and spectrophotometric methods, as well as emerging strategies for extraction, encapsulation, and delivery to enhance stability and bioavailability. Finally, the integration of chestnut and grapevine by-products into nutraceuticals, functional foods, and natural preservatives is critically examined from technological, safety, regulatory, and sustainability perspectives. Overall, this synthesis underscores the potential of these underutilised biomass streams as multifunctional raw materials that support waste valorisation, resource efficiency, and the development of next-generation health-promoting ingredients aligned with circular bioeconomy principles. Full article

This study systematically compared the growth performance, nutrient composition, accumulation and speciation of selenium (Se), and in vitro bioaccessibility in yellow mealworm (Tenebrio molitor L.) larvae, which were reared on substrates supplemented with selenite (Se⁴⁺) and selenate (Se⁶⁺) at concentrations of 0, 5, 10, and 20 mg/kg over 28 days. The results showed that high Se concentrations (≥10 mg/kg) significantly reduced larval biomass, with Se⁶⁺ having a slightly stronger inhibitory effect than Se⁴⁺. The mealworms effectively accumulated Se in a dose- and form-dependent manner. Peak total Se concentrations were observed on day 14, after which there was a decline, suggesting the presence of potential elimination mechanisms, such as moulting. The bioaccumulation factors (BAFs) were all below 1, indicating its limited enrichment capacity for both Se⁴⁺ and Se⁶⁺. Nutrient composition was altered, with both Se forms stimulating crude protein and polysaccharide synthesis while inhibiting fat accumulation. Mineral content (Mg, Fe, Zn) was also modulated, with differences observed between the Se⁴⁺ and Se⁶⁺ treatments. Notably, mealworms exhibited a remarkable ability to biotransform inorganic Se into organic forms, with organic Se proportions exceeding 79% in all treatments. Selenate was more efficiently bio-converted, yielding a higher proportion of organic Se. In vitro gastrointestinal digestion revealed significantly higher Se bioaccessibility from Se⁶⁺-treated mealworms (up to 85.12%) than from Se⁴⁺-treated ones (up to 60.67%). Analysis of the bioaccessible fraction by Se speciation identified SeCys₂ as the dominant compound (>92% of the detected species), with much lower levels of SeMet. Trace amounts of unmetabolised Se⁶⁺ were only detected in the Se⁶⁺-exposed groups. These findings highlight T. molitor as an efficient bioreactor for producing bioaccessible, organically bound Se, primarily as SeCys₂, with Se⁶⁺ being the more favourable precursor for generating a high-quality, bioavailable source of Se for potential use in feed or food. Full article

In humans, the bioactivity of polyphenols is highly dependent on dose intake and their interactions with the gastrointestinal tract and gut microbiota, which metabolize polyphenols into bioactive or inactive derivatives. Polyphenols are only partially absorbed in the small intestine, where enzymatic hydrolysis releases aglycone forms that may cross the gut barrier. A significant proportion of polyphenols escapes absorption and reaches the colon, where resident microbes convert them into simpler phenolic metabolites. Such molecules are often more bioavailable than the parent compounds and can enter systemic circulation, leading to distant effects. Although higher polyphenol consumption has been associated with preventive and therapeutic outcomes, even low intake or poor intestinal absorption may still confer benefits, as polyphenols in the colon can positively modulate gut microbiota composition and function, contributing to favorable shifts in the microbial metabolome. These interactions can influence host metabolic, immune, and neurological pathways, particularly through the gut–liver–brain axis. To provide a comprehensive understanding of these relationships, this review examines the dose-related activity of polyphenols, their microbiota-mediated biotransformation, their bioavailability, and the health effects of their metabolites, while also presenting a comparative overview of key studies in the field. We underscore the importance of integrating microbiome and polyphenol research to recapitulate and contextualize the health benefits of dietary polyphenols. Full article

In vitro cartilage explant culture has been used to assess nutraceuticals on cartilage responses to inflammatory stimuli. However, applying extracts of nutraceuticals directly to cartilage explants does not account for effects of digestion and hepatic biotransformation, or selective exclusion of product metabolites from joint fluid by the synovial membrane. The current study produced a simulated biological extract of a common nutraceutical (glucosamine; G_sim) by exposing it to a simulated upper gastrointestinal tract digestion, hepatic biotransformation by liver microsomes, and purification to a molecular weight cut-off of 50 kDa. This extract was then used to condition cartilage explants cultured for 120 h in the presence or absence of an inflammatory stimulus (lipopolysaccharide). Media samples were analyzed for prostaglandin E₂ (PGE₂), glycosaminoglycan (GAG), and nitric oxide (NO). Tissue was digested and analyzed for GAG content and stained for viability. Conditioning of explants with G_sim significantly reduced media GAG in stimulated and unstimulated explants and reduced nitric oxide production in unstimulated explants. These data provide evidence for the value of glucosamine in protecting cartilage from deterioration following an inflammatory challenge, and the model improves applicability of these in vitro data to the in vivo setting. Full article

Background/Objectives: Capsaicin is the principal pungent compound in chili peppers and is increasingly recognized as a multifunctional phytochemical with systemic effects beyond its sensory properties. It has been linked to metabolic regulation, neuroprotection, inflammation control, and cancer modulation. This review aims to provide an integrative synthesis of capsaicin’s metabolism, its interaction with the gut microbiome, and its physiological implications across organ systems. Methods: We conducted a critical literature review of recent in vivo and in vitro studies exploring capsaicin’s metabolic fate, biotransformation by host enzymes and gut microbes, tissue distribution, and molecular pathways. The literature was analyzed thematically to cover gastrointestinal absorption, hepatic metabolism, microbiota interactions, and systemic cellular responses. Results: Capsaicin undergoes extensive hepatic metabolism, producing hydroxylated and dehydrogenated metabolites that differ in transient receptor potential vanilloid type 1 (TRPV1) receptor affinity and tissue-specific bioactivity. It crosses the blood–brain barrier, alters neurotransmitter levels, and accumulates in brain regions involved in cognition. In addition to its systemic effects, capsaicin appears to undergo microbial transformation and influences gut microbial composition, favoring short-chain fatty acid producers and suppressing pro-inflammatory taxa. These changes contribute to anti-obesity, anti-inflammatory, and potentially anticancer effects. Dose-dependent adverse outcomes, such as epithelial damage or tumor promotion, have also been observed. Conclusions: Capsaicin represents a diet-derived bioactive molecule whose systemic impact is shaped by dynamic interactions between host metabolism and the gut microbiota. Clarifying its biotransformation pathways and context-specific effects is essential for its safe and effective use in metabolic and neurological health strategies. Full article

BG136, a β-1,3/1,6-glucan derived from Durvillaea antarctica, is an injectable anticancer drug and has entered Phase II clinical trials. Rational oral formulation design is a pivotal focus for our future drug development research; therefore, elucidating the gastrointestinal fate of BG136 becomes imperative. This study investigated the stability and biotransformation of BG136 via in vitro digestion and gut microbiota fermentation. The results confirmed BG136’s structural integrity, resistance to degradation in a highly acid environment and by gastrointestinal tract enzymes. In contrast, BG136 was degraded by intestinal bacteria into mid-size fragments along with smaller oligosaccharides. Additionally, the biotransformation process notably elevated total short-chain fatty acids (SCFAs) to 38.37 ± 3.29 mM, representing a 59.4% increase versus controls (24.08 ± 2.29 mM), with propionic acid exhibiting the most substantial increase. Meanwhile, the process was accompanied by significant microbial regulation, including an increase in beneficial genera (Lactobacillus, Enterococcus) and a reduction in Lachnoclostridium populations. Overall, these findings systematically map the oral bioavailability challenges and prebiotic potential of BG136, highlighting its microbiota-modulating capacity through species-specific ecological regulation, providing insights into oral drug development for BG136. Full article

Background: Olive leaves are a rich source of polyphenols, predominantly secoiridoids, flavonoids, and simple phenols, which exhibit various biological properties. Extracts prepared from olive leaves are associated with hypoglycemic, hypotensive, diuretic, and antiseptic properties. Upon ingestion, a substantial fraction of these polyphenols reaches the colon where they undergo extensive metabolism by the gut microbiota. Host characteristics, like age, can influence the composition of the gut microbiome, potentially affecting the biotransformation of these compounds. Therefore, it can be hypothesised that differences in the gut microbiome between young and elderly individuals may impact the biotransformation rate and the type and amount of metabolites formed. Methods: An in vitro biotransformation model was used to mimic the conditions in the stomach, small intestine and colon of two age groups of healthy participants (20–30 years old, ≥65 years old), using oleuropein as a single compound and an olive leaf extract as test compounds. The bacterial composition and metabolite content were investigated. Results: The study revealed that, while the same metabolites were formed in both age groups, in the young age group, less metabolite formation was observed, likely due to a reduced viable cell count. Most biotransformation reactions took place within the first 24 h of colon incubation, and mainly, deglycosylation, hydrolysis, flavonoid ring cleavage, and demethylation reactions were observed. A bacterial composition analysis showed a steep drop in α-diversity after 24 h of colon incubation, likely due to favourable experimental conditions for certain bacterial species. Conclusions: Both age groups produced the same metabolites, suggesting that the potential for polyphenols to exert their health-promoting benefits persists in healthy older individuals. Full article

Luteolin (Lut) and apigenin (Apn), flavones present in various edible plants, exhibit diverse antioxidant and pharmacological activities but have limited in vivo efficacy due to low water solubility and poor bioavailability. Here, we generated luteolin and apigenin monophosphate derivatives (LutPs and ApnPs) individually via microbial biotransformation. We then characterized their physicochemical properties and evaluated their in vitro and in vivo pharmacokinetics and bioavailability. Both LutPs and ApnPs showed enhanced solubility and dissolution and remained stable in simulated gastrointestinal conditions. Additionally, they efficiently reverted to parental forms via alkaline phosphatase in Caco-2 cells. Following oral administration in rats, LutPs and ApnPs exhibited higher plasma exposure to both aglycone and conjugated forms compared to Lut and Apn. Notably, the in vivo biotransformation of Apn to Lut was observed in all apigenin-related groups. Our study suggests that flavone monophosphates are effective alternatives with enhanced bioavailability, providing insights for the potential application of emerging bioactive nutraceuticals. Full article

Xanthohumol (1) is a major prenylated flavonoid in hops (Humulus lupulus L.) which exhibits a broad spectrum of health-promoting and therapeutic activities, including anti-inflammatory, antioxidant, antimicrobial, and anticancer effects. However, due to its lipophilic nature, it is poorly soluble in water and barely absorbed from the gastrointestinal tract, which greatly limits its therapeutic potential. One method of increasing the solubility of active compounds is their conjugation to polar molecules, such as sugars. Sugar moiety introduced into the flavonoid molecule significantly increases polarity, which results in better water solubility and often leads to greater bioavailability. Entomopathogenic fungi are well known for their ability to catalyze O-glycosylation reactions. Therefore, we investigated the ability of selected entomopathogenic filamentous fungi to biotransform xanthohumol (1). As a result of the experiments, one aglycone (2) and five glycosides (3–7) were obtained. The obtained (2″E)-4″-hydroxyxanthohumol 4′-O-β-D-(4‴-O-methyl)-glucopyranoside (5) has never been described in the literature so far. Interestingly, in addition to the expected glycosylation reactions, the tested fungi also catalyzed chalcone–flavanone cyclization reactions, which demonstrates chalcone isomerase-like activity, an enzyme typically found in plants. All these findings undoubtedly indicate that entomopathogenic filamentous fungi are still an underexploited pool of novel enzymes. Full article