Search Results (459)

Adverse childhood experiences are associated with long-term metabolic disturbances, yet their effects on the exocrine pancreas remain poorly understood. Using maternal separation (MS) as a model of early-life stress, this study examined whether MS modifies the exocrine pancreatic response to a post-weaning high-fat diet (HFD) in male C57BL/6 mice. Animals were exposed to MS or standard rearing conditions and fed a control diet or HFD for 16 weeks. Body and pancreatic mass, plasma amylase and lipase activities, exocrine pancreatic histopathology, and apoptosis were assessed. HFD increased body mass and reduced the pancreas-to-body mass ratio independently of MS, without altering absolute pancreatic mass. Lipase activity increased significantly in response to both MS and HFD, whereas amylase showed a non-significant upward trend. Histopathological analysis revealed condition-dependent exocrine pancreatic remodeling, including acinar hypertrophy, autophagic vacuolization, focal necrosis, vascular alterations, interstitial edema, and ductal changes. These alterations were mild in HFD-only mice but more pronounced in MS-exposed animals, particularly when combined with HFD. Apoptosis was strongly influenced by early-life stress and modulated by diet, with significant effects of MS and the MS × diet interaction. Overall, early-life stress induces persistent structural and functional alterations in the exocrine pancreas, increasing susceptibility to nutritional challenges in adulthood. Full article

The global rise in obesity and associated metabolic disorders has fueled the demand for safe, multi-target therapeutics derived from natural sources. In this study, an artificial neural network combined with a genetic algorithm (ANN-GA), was employed to optimize the ultrasound-assisted extraction of loquat leaf extract (LLE). The optimal parameters—0.6% Tween 80, 328 W ultrasonic power, and 49 °C—enhanced extraction efficiency while minimizing energy consumption and surfactant use. In vitro, LLE exhibited potent dose-dependent inhibition of α-glucosidase (IC₅₀ = 3.75 μg/mL, 21.6-fold stronger than acarbose) and pancreatic lipase (IC₅₀ = 78.3 μg/mL), indicating strong inhibitory activity against these digestive enzymes. In high-fat diet-induced obese mice, LLE supplementation dose-dependently reduced body weight gain, serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose while elevating high-density lipoprotein cholesterol (HDL-C). In addition, LLE ameliorated liver injury (decreased ALT/AST) and oxidative stress (lowered MDA, increased SOD). These findings highlight LLE as a promising multi-target natural product for managing obesity and related metabolic disorders. Full article

Background: Type 2 diabetes (T2DM) is a chronic metabolic disease closely associated with insulin resistance (IR) and disturbances in glucose and lipid metabolism. Bioactive peptides derived from food are attracting increasing research attention as candidates for nutritional supplements or functional food ingredients that improve metabolic health. This study evaluated the functional food-related properties of YPWTQ (CP4), a novel peptide derived from donkey blood, and its ability to alleviate insulin resistance in HepG2 cells. Methods: CP4 was characterized based on its hemolytic activity, stability under simulated gastrointestinal digestion conditions, inhibitory activity against α-glucosidase and Pancreatic lipase, and free radical scavenging capacity (DPPH·, ABTS⁺·, and O₂⁻·). Its effects on glucolipid metabolism and oxidative stress were examined in a glucosamine-induced insulin-resistant HepG2 cell model. Candidate signaling pathways associated with CP4 treatment were explored through transcriptomic and metabolomic analyses, combined with RT-qPCR technology. Results: CP4 exhibited low hemolytic activity and remained stable after 4 h of simulated gastrointestinal digestion. It inhibited α-glucosidase and Pancreatic lipase and exhibited antioxidant activity. In insulin-resistant HepG2 cells, CP4 increased glucose consumption, glycogen content, and cell survival, while reducing triglyceride accumulation, malondialdehyde levels, and reactive oxygen species (ROS) production. Mult omics analysis indicates that these phenotypic effects may be associated with coordinated changes in the PI3K-Akt, AGE-RAGE, Rap1, and Ras signaling pathways, as well as related genes and metabolites. Conclusions: These findings suggest that CP4, as a food-derived bioactive peptide candidate, warrants further investigation into its potential applications in the field of metabolic health. Full article

This study optimized supercritical fluid extraction (SC-CO₂) parameters for Boswellia sacra leaves to evaluate how extraction thermodynamics influence subsequent pharmacological bioactivity. Using a multi-parametric approach, extracts obtained at 40 °C and 80 °C (100 bar) were profiled via HPLC-DAD and evaluated using in vitro antimicrobial, pancreatic lipase inhibition, and Caco-2 cell antiproliferative assays. HPLC analysis revealed that the 40 °C threshold preserved chemical diversity (17 active peaks, retaining higher caffeic acid and rutin concentrations), whereas 80 °C conditions caused severe compound degradation. Consequently, the 40 °C extracts exhibited significantly enhanced biomedical potencies over the 80 °C variants, demonstrating superior microbiostatic activity against Gram-positive bacteria and Candida albicans (MIC = 15.62 µg/mL), stronger porcine pancreatic lipase inhibition (IC₅₀ = 17.21 µg/mL), and greater antiproliferative efficacy against human colorectal adenocarcinoma cells (IC₅₀ = 109.47 µg/mL). Ultimately, maintaining low thermal thresholds during green extraction is critical to preserving the integrated polyphenolic architecture of B. sacra required for multi-targeted antimicrobial, anti-obesity, and anticancer therapeutics. Full article

Pancreatic lipase activity depends strongly on interfacial conditions created by bile salts, motivating the search for plant-derived surfactants that may modulate lipid digestion. In our previous work, ginseng root and horse chestnut seed extracts were identified as potent stimulators of pancreatic lipase. Here, we expanded this investigation to additional Panax and Aesculus species and to saponin-rich extracts from Acer pseudoplatanus, Herniaria glabra, and Polypodium vulgare. Extracts were evaluated for effects on pancreatin lipolysis in relation to equilibrium surface tension, surface rheology, and olive-oil emulsion stability. Antiradical and antioxidant activities, total phenolic content, and flavonoid content were also determined. White ginseng root extract (Panax ginseng) produced the strongest stimulation, followed by horse chestnut seed extract (Aesculus hippocastanum), whereas Aesculus marylandica seed peel extract inhibited lipase activity. Several extracts showed concentration-dependent switching from weak inhibition to stimulation. Antioxidant and antiradical activities correlated strongly with total phenolic content, while emulsion stabilization did not correlate with lipase stimulation. Molecular modeling showed that cholate, escinescin Ia, osladin, and ginsenoside Rg1 did not persistently occlude the catalytic pocket, whereas several other saponins showed active-site blocking. Together, the results support a mechanism in which saponin-rich extracts regulate lipolysis through combined interfacial effects and compound-specific enzyme interactions. Full article

Digestive enzymes such as pancreatic lipase (PL), α-glucosidase (AG), and α-amylase (AA) play key roles in the hydrolysis of dietary lipids and carbohydrates and are therefore relevant biochemical targets for evaluating compounds with potential to modulate postprandial metabolic responses. Neurolaena lobata (L.) R. Br. ex Cass. (Asteraceae) is a neotropical medicinal species traditionally used for several health-related conditions, including metabolic complaints. This study evaluated the in vitro inhibitory activity of the hydroalcoholic extract, selected VLC fractions, and isolated metabolites from N. lobata leaves against PL, AG, and AA. Enzyme inhibition screening of the extract and VLC fractions was used to select fractions for phytochemical investigation, affording six known metabolites: the sesquiterpene lactones neurolenin B (C1) and lobatin A (C2), the benzoic acid derivatives p-hydroxybenzoic acid (C3) and 3,4-dihydroxybenzoic acid (C4), and the flavonoids 6-hydroxykaempferol 3,7-dimethyl ether (C5) and quercetagetin 3,7-dimethyl ether (C6). The hydroalcoholic extract and the MeOAc and iPrOH fractions inhibited PL, AG, and AA. Among the isolated compounds, C1, C2, C5 and C6 inhibited PL and AG, with IC₅₀ values ranging from 134 to 615 µM and from 170 to 639 µM, respectively, whereas all compounds showed weak AA inhibition. Exploratory kinetic analysis yielded apparent inhibition profiles mainly consistent with competitive behavior; C6 showed an apparent profile consistent with noncompetitive inhibition against AG under the assay conditions used. These findings expand the phytochemical and in vitro bioactivity profile of N. lobata and provide preliminary evidence of digestive enzyme modulation in isolated enzyme systems, without establishing therapeutic efficacy. Full article

Primary hyperlipoproteinemias represent a heterogeneous group of inherited lipid metabolism disorders characterized by persistent abnormalities in plasma lipoproteins, a markedly increased risk of premature atherosclerotic cardiovascular disease (ASCVD) and, in selected phenotypes, acute pancreatitis. Traditionally classified according to the Fredrickson phenotypic system, these disorders are now increasingly understood through a multidimensional framework integrating molecular genetics, intracellular lipid trafficking, inflammatory signaling, and systemic metabolic regulation. Recent advances have identified both monogenic and polygenic determinants underlying disease expression, including pathogenic variants affecting LDLR, APOB, PCSK9, APOE, and lipoprotein lipase pathways, as well as the cumulative contribution of multiple common lipid-associated variants. Furthermore, emerging evidence highlights the role of endoplasmic reticulum stress, oxidative imbalance, adipose–hepatic crosstalk, intestinal lipid absorption, and inflammatory mediators in modulating lipoprotein metabolism and cardiovascular risk. Novel regulators such as angiopoietin-like proteins (ANGPTLs), microRNAs, and pathways involved in cholesterol efflux and remnant lipoprotein clearance have further refined our understanding of disease heterogeneity and therapeutic responsiveness. Familial hypercholesterolemia and familial combined hyperlipidemia exemplify the complex interplay between genetic susceptibility, metabolic dysfunction, and environmental influences that shape phenotype severity and long-term cardiovascular outcomes. Advances in diagnostic strategies, including genetic testing, polygenic risk scores, apolipoprotein profiling, and vascular imaging, have significantly improved risk stratification and personalized management. Simultaneously, innovative therapies—including PCSK9 inhibitors, ANGPTL3-targeted agents, antisense oligonucleotides, and RNA-silencing technologies—are reshaping treatment paradigms and expanding options for high-risk patients. This chapter synthesizes contemporary insights into the pathogenesis of primary hyperlipoproteinemias, emphasizing the transition from traditional lipid-based classification toward precision medicine approaches focused on lifetime cardiovascular risk, molecular characterization, and individualized therapeutic intervention. Full article

Background: The therapeutic potential of many natural products, including curcumin (CUR), betulinic acid (BA), and oleanolic acid (OA), is limited by poor oral exposure caused by low aqueous solubility, metabolic instability, and/or first-pass metabolism. Lipid–drug conjugate (LDC) strategies that mimic endogenous dietary lipid processing may provide a useful approach for improving oral absorption and lymphatic transport. Methods: A 1,3-diolein-based lipidic promoiety (IN-4) was synthesized and conjugated to curcumin, betulinic acid, and oleanolic acid to generate three representative LDCs: CUR-PRO, BA-PRO, and OA-PRO. Their oral pharmacokinetic behavior was evaluated in rats. For CUR-PRO, matched-vehicle comparisons across three oral vehicles were performed, together with mesenteric lymph duct cannulation and in vitro stability/conversion studies in simulated gastrointestinal media, rat liver microsomes, and rat plasma. Results: All three prodrugs were successfully synthesized and showed improved systemic exposure to the corresponding parent-drug-related analytes under the tested conditions. For CUR-PRO, dose-normalized AUC_0-last of released curcumin was markedly higher than direct curcumin administration across all three vehicles (increases of 15.0-, 70.9-, and 54.3-fold), and intact CUR-PRO was also detected in plasma. Mesenteric lymph sampling showed that CUR-PRO dosing, but not free-curcumin dosing, generated detectable curcumin-related signals under the present analytical conditions. In vitro, no free curcumin was detected during CUR-PRO incubation in enzyme-free simulated gastrointestinal media; CUR-PRO underwent rapid depletion in pancreatic-lipase-supplemented medium, showed greater microsomal stability than curcumin, and displayed plasma conversion that was markedly accelerated by exogenous LPL. BA-PRO and OA-PRO also increased systemic exposure of their released parent drugs, with 16.0- and 38.4-fold dose-normalized AUC_0-last increases, respectively. Conclusions: These findings provide proof-of-concept evidence that 1,3-diolein-based lipidation can improve the oral exposure of selected poorly water-soluble natural products. The lymphatic transport data provide qualitative evidence supporting lymphatic access of CUR-PRO, although the quantitative contribution of this pathway to the overall exposure increase remains to be established. Full article

Medicinal plants are being investigated as a source of compounds with biological activities related to diabetes. The antidiabetic properties of the plant Carica papaya have been reported in experimental models. This study aimed to evaluate the phytochemical composition, antioxidant activity, and inhibitory activity of extracts from C. papaya leaves against α-glucosidase and pancreatic lipase. Plant material was collected in Tabasco, Mexico, and extracted by sequential maceration with solvents of increasing polarity: hexane, dichloromethane, methanol, and methanol:water. The extracts were fractionated by column chromatography, and the most active fractions were selected for further purification. The phytochemical identification of the active compounds was performed, and their structures were elucidated using spectroscopic and spectrometric techniques. The methanolic extract, rich in phenols and flavonoids, showed the highest antioxidant capacity (DPPH: 8.99 mmol TE/g; ABTS: 35.94 mmol RE/g; FRAP: 48.62 mmol Fe²⁺/g). The hydroalcoholic extract exhibited α-glucosidase inhibitory activity (38.44%), and bioassay-guided fractionation led to the identification of clitorin. The dichloromethane extract showed pancreatic lipase inhibition (52.2%), and the most active fraction contained loliolide. These findings demonstrate that C. papaya leaves contain bioactive compounds with antioxidants and digestive enzyme inhibitory activities, suggesting they could be candidates for further research in the management of diabetes. Full article

Many bioactive constituents of medicinal plants depend on microbial biotransformation for their pharmacological activity, positioning postbiotics from plant substrates as microbially matured phytomedicines. An emerging framework integrates prebiotic phytochemicals with probiotic strains to modulate gut microbiota and host health. In this study, we explored the functional properties of heat-inactivated Lactobacillus strains following the fermentation of oligosaccharides obtained from sesame hulls (Sesamum indicum L.), underutilised agro-industrial residues. Cell-wall oligosaccharides were obtained by alkaline or enzymatic (Celluclast^® 1.5 L (Novonesis, Copenhagen, Denmark)) extraction with Ultraflo^® L (Novonesis, Copenhagen, Denmark) hydrolysis and fermented with Lactobacillus acidophilus, L. casei, or L. paracasei. Heat-inactivated pre-postbiotic preparations were profiled for antioxidant capacity, inhibition of metabolic enzymes implicated in obesity and type 2 diabetes, and anti-Helicobacter pylori urease activity. Moreover, these preparations were incorporated into a barley malt (Hordeum vulgare L.) beverage. Bioactivity was strain- and substrate-dependent: L. casei-derived postbiotics most strongly inhibited pancreatic lipase (47.82%) and α-glucosidase (52.14%); L. acidophilus most strongly inhibited α-amylase (43.67%); and L. paracasei exhibited the strongest urease inhibition (20.66%). All strains displayed enhanced antioxidant activity, with ABTS scavenging reaching 87.02%. The supplemented beverages improved antioxidant activity by ~20%. The fermentation of these oligosaccharides thus yields a microbially matured phytomedicine with multi-target activity, supporting postbiotics as active mediators of plant-based therapeutics. Full article

Blackcurrant (Ribes nigrum L.) fruits and their by-products represent valuable sources of bioactive compounds. This study compared fruits, juice, seeds, oil, and leaves with respect to their content of selected bioactive components, potential intestinal availability of polyphenols estimated by dialysis, and in vitro biological activities. Blackcurrant leaves contained several-fold higher levels of polyphenols in the dialyzable fraction (651.3 mg/100 g) than fruits (255.1 mg/100 g) and juice (261.4 mg/100 g). Seeds exhibited the strongest antioxidant activity among all matrices, reaching 13.3, 10.9 and 11.4 mmol Trolox/100 g in the ABTS, FRAP and ORAC assays, respectively. Hydrophilic fractions of juice and seeds showed notably stronger α-amylase inhibition (IC₅₀ < 0.01 mg/mL) than the antidiabetic drug acarbose (IC₅₀ = 0.35 mg/mL). Juice also demonstrated higher pancreatic lipase inhibition (IC₅₀ = 0.01 mg/mL) compared with Orlistat (IC₅₀ = 0.15 mg/mL) and effectively inhibited acetylcholinesterase, butyrylcholinesterase, and 15-lipoxygenase (IC₅₀ = 0.11, 0.03, and 0.02 mg/mL, respectively). These results indicate that various blackcurrant matrices possess strong biological activity and may serve as promising functional food ingredients or sources of health-promoting compounds. Full article

Background/Objectives: Red beetroot (Beta vulgaris L.) is recognized for its antioxidant, anti-inflammatory, and metabolic properties. This study evaluated the effects of two beetroot cultivars (Boldor and Wodan) on blood serum parameters, body composition, and organ weights in male WKY rats fed a low-protein diet (LPD, 8.8% protein). Methods: Five-week-old male rats were maintained on an LPD for 8 weeks and subsequently continued on the LPD diet supplemented with 4% dried beetroot for 45 days. The experimental diets included beetroot from the Boldor and Wodan cultivars, either treated or untreated with a plant growth stimulator during cultivation. Results: Foliar application of the selenium-based plant growth stimulator did not significantly increase selenium or other element concentrations in beet roots. Elemental analysis showed higher levels of Fe, Zn, Cu, Cr, Pb, As, Cd, and Sb in the Wodan group, while Boldor increased Cr, Pb, and As; Ni and Se remained unchanged. Beetroot supplementation significantly affected 14 of the 30 measured biochemical parameters, including biomarkers of liver function (ALT, ALP, total bilirubin, albumin, and total protein), renal function (uric acid), pancreatic activity (amylase and lipase), electrolyte balance (sodium, potassium, and chloride), mineral metabolism (calcium), inflammatory status (CRP), and nutritional metabolism (iron). Conversely, no significant effects were observed on lipid profile parameters or biomarkers of cardiac and skeletal muscle injury. Among the beetroot cultivars evaluated, Wodan exerted distinct effects relative to Boldor, resulting in higher circulating total bilirubin and potassium concentrations, alongside reduced uric acid and lipase levels in treated rats. Boldor supplementation significantly increased body weight gain and fat mass, with a trend toward higher lean mass, and increased kidney weight. Wodan did not significantly affect body weight but increased kidney and spleen mass. Feed intake was similar across groups. No changes in cardiovascular function were observed ex vivo. Conclusions: Beetroot supplementation modulated multiple metabolic and physiological biomarkers in rats fed a low-protein diet, with distinct cultivar-specific effects, underscoring the importance of cultivar selection for optimizing functional dietary interventions. Full article

Severe acute pancreatitis (SAP) is a life-threatening inflammatory disorder characterized by high mortality and limited therapeutic options. Alginate oligosaccharide (AOS), a marine-derived bioactive polysaccharide, exhibits prebiotic, anti-inflammatory and antioxidant properties that are effective against various inflammatory diseases. In this study, a mouse model of SAP was established by intraperitoneal injection of cerulein (100 μg/kg) and lipopolysaccharide (5 mg/kg), and the mice were pretreated with AOS (200 mg/kg) by gavage for 4 consecutive weeks to explore the potential protective efficacy and underlying mechanisms. The results shown that AOS attenuated the severity of SAP, as evidenced by reduced serum amylase and lipase levels, as well as alleviated histopathological injury in both pancreatic and ileal tissues. AOS suppressed the overproduction of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in serum, pancreas, and ileum at protein or mRNA levels. Moreover, AOS effectively diminished pancreatic and ileal inflammatory infiltration and oxidative stress in SAP mice, accompanied by inhibited the TLR4/MyD88/NF-κB pathway and activated the Nrf2/HO-1 antioxidant axis. Furthermore, AOS restored intestinal barrier integrity, as manifested by upregulated expression of tight junction proteins (claudin-1, occludin, ZO-1), reduced serum diamine oxidase, and decreased bacterial translocation from the gut to the pancreas. It was revealed by 16S rRNA sequencing that AOS ameliorated SAP-induced gut dysbiosis by restoring microbial diversity, normalizing the Firmicutes/Bacteroidetes ratio, enriching beneficial genera (Lactobacillus, Blautia), and enhancing cecal short-chain fatty acid (acetic, propionic, butyric acid) production. Collectively, our findings demonstrate that AOS exerts comprehensive protective effects against SAP through suppression of inflammatory signaling and oxidative stress, as well as restoring gut homeostasis. These results suggest that AOS may serve as a promising prebiotic-based nutritional strategy for the management of SAP. Full article

Background/Objectives: Betanin (Bet), a natural compound, exhibits potent antioxidant and metabolic regulatory properties, yet its effect on cellular glucose utilization remains unclear. This study investigated, for the first time, the impact of Bet on glucose consumption and the activation of key carbohydrate–catabolic pathways in human erythrocytes. Methods: In vitro assays were performed to evaluate enzyme inhibition and activation. Human erythrocytes were incubated with Bet to assess glucose consumption. Enzyme activities were measured spectrophotometrically, and molecular docking was used to analyze binding interactions. Results: Our results demonstrate that Bet inhibits digestive enzymes in a dose-dependent manner, with maximal inhibition at 90 µg/mL for pancreatic lipase and 70 µg/mL for α-amylase, showing IC₅₀ values of 48.8 and 31.9 µg/mL, respectively, supported by strong binding affinities of −9.3 and −8.9 Kcal/mol. These interactions are stronger than those of orlistat (−6.9 Kcal/mol) and acarbose (−7.7 Kcal/mol). Bet also induced the activity of AMPK with an IC₅₀ of 1.83 µg/mL and a BE of −7.90 Kcal/mol, compared to the specific AMPK activator A-769662, which had an IC₅₀ of 1.29 µg/mL and a binding energy of −10.0 Kcal/mol. Consequently, Bet stimulated key glycolytic enzymes, reaching maximal activation (~62%) at 1.4 µg/mL for hexokinase (HK) and glucose-6-phosphate dehydrogenase (G6PD), and at 1.6 µg/mL for pyruvate kinase (PK), supported by binding energies of −7.2, −7.5, and −9.0 Kcal/mol and AC₅₀ values of 0.87, 0.98, and 0.91 µg/mL, respectively. Moreover, Bet enhanced key Krebs cycle enzymes (IDH, SDH, MDH, LDH) in a dose-dependent manner, with AC₅₀ values of 0.76, 0.80, 0.72, and 0.52 µg/mL and strong binding energies (−7.8, −7.8, and −8.4 Kcal/mol), reaching maximal activation near 1.4 µg/mL. Bet also increased glucose consumption by human erythrocytes. Conclusions: Bet enhances glucose utilization by inhibiting digestive enzymes and activating intracellular metabolic pathways, suggest potential metabolic regulatory effects. Full article

Obesity and its metabolic complications represent a major global health challenge, and food-derived bioactive peptides are emerging as promising dietary interventions. In this study, two hemp seed protein-derived tetrapeptides with pancreatic lipase (PL) and cholesterol esterase (CE) inhibitory activity, APAM and RLPA, were co-administered with a high-fat diet (HFD) to male C57BL/6J mice at 25 and 100 mg/kg body weight for 10 weeks. Both peptides dose-dependently alleviated HFD-induced body weight gain, visceral fat accumulation, hepatic steatosis, dyslipidemia, hyperglycemia, and systemic inflammation. Mechanistically, both peptides inhibited intestinal PL and CE activities and enhanced fecal lipid excretion, supporting direct suppression of intestinal fat digestion. 16S rRNA gene sequencing revealed partial restoration of HFD-disrupted gut microbiota, with APAM preferentially enriching Bifidobacterium and Roseburia, while RLPA promoted Akkermansia and Lactobacillus, accompanied by differential improvements in fecal short-chain fatty acid (SCFA) profiles. Hepatic transcriptomics identified the PPAR signaling pathway as a shared regulatory hub, and multi-omics integration revealed significant correlations linking gut microbiota, SCFA production, hepatic gene expression, and metabolic phenotypes. These findings suggest a dual-pathway anti-obesity mechanism integrating intestinal lipid digestion inhibition with gut–liver axis modulation, and highlight hemp seed protein-derived peptides as potential functional food ingredients for obesity prevention. Full article