Intestinal Absorption Research Articles

Translating plasma citrulline concentration in clinical practice: Role of cross-sectional assessment in adult patients with short bowel syndrome

BackgroundCross-sectional plasma citrulline concentration (CIT) is considered a marker of enterocyte mass. The role of CIT in clinical practice in patients with short bowel syndrome (SBS) is not clearly defined. AimTo assess the accuracy of CIT to discriminate SBS from healthy controls (HC) and SBS with intestinal failure (SBS-IF), requiring intravenous supplementation (IVS), from SBS with intestinal insufficiency (SBS-II). MethodsCross-sectional study on unselected outpatients (31 SBS-II, 113 SBS-IF) and 19 healthy controls (HC). Demographic data, SBS characteristics, nutritional status, oral intake, intestinal fat absorption, renal function and IF severity, categorized by the volume of the required IVS, were collected at time of CIT evaluation (µmol/L). Data as mean±SD. ResultsCIT was 36.6 ± 6.0 in HC, 30.2 ± 14.0 in SBS-II and 18.8 ± 12.3 in SBS-IF (p < 0.001). CIT cutoff was 31 for the diagnosis of SBS (sensitivity 79 %, specificity 89 %), and 14 for the discrimination between SBS-IF and SBS-II (sensitivity 100 %, specificity 51 %). Wide ranges of CIT were observed in all SBS-IF severity categories. ConclusionsIn unselected SBS patients, CIT was accurate to diagnose SBS, had high sensitivity to diagnose SBS-IF but showed low specificity for SBS-II. In SBS-IF, CIT was not an accurate marker of IF severity.

Antidiabetic potentials of crude and purified sulphated polysaccharides isolated from Gracilaria gracilis, a seaweed from South Africa

Over 90 % of all cases of diabetes that have been diagnosed are type 2 diabetes (T2D), a disease exacerbated by an increase in sedentary behaviour, bad eating habits, and obesity. This study investigated the antidiabetic properties of Gracilaria gracilis, using in vitro and ex vivo experimental models. The sulphated polysaccharides (SPs) from crude extracts of the seaweed powder was prepared via hot (100°C) and cold (25°C) aqueous extraction procedures before purification via an anion exchange chromatographic technique. Both the crude and purified extracts were characterised by Fourier-transform infrared spectroscopy (FT-IR), LC-MS analysis, and Nuclear Magnetic Resonance (NMR) spectroscopy. The crude cold-aqueous and purified hot-aqueous SPs from G. gracilis had the strongest α-glucosidase inhibitory effect with IC50 value of 0.15 and 0.07 mg/ml, respectively. The purified cold-aqueous SP was the most potent inhibitor of α-glucosidase with an IC50 value of 0.17 mg/ml. The crude and purified SP-rich extracts inhibited pancreatic lipase (hot aqueous SP = 0.03 mg/ml) activity and effectively stimulated glucose uptake in yeast cells. Moreover, they showed significantly (p < 0.05) better intestinal glucose absorption inhibitory properties at the highest concentration (1 mg/ml) and displayed significantly (p < 0.05) better muscle glucose uptake compared to the commercial antidiabetic drug, metformin, at the same concentration. Overall, the current findings indicate that G. gracilis SPs may inhibit carbohydrate-hydrolysing enzymes, limit the release of simple sugars from the gut whilst effectively stimulating the use of glucose by peripheral tissue thus may be suitable to develop antidiabetic food supplements after further animal and clinical trials.

Variation of LDL cholesterol in response to the replacement of saturated with unsaturated fatty acids: a nonrandomized, sequential dietary intervention; the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention (“RISSCI”-1) study

BackgroundSerum low density lipoprotein (LDL) cholesterol shows marked interindividual variation in response to the replacement of saturated fatty acids (SFAs) with unsaturated fatty acids (UFAs). ObjectivesTo demonstrate the efficacy of United Kingdom guidelines for exchanging dietary SFAs for UFAs, to reduce serum LDL cholesterol and other cardiovascular disease (CVD) risk factors, and to identify determinants of the variability in LDL cholesterol response. MethodsHealthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2), consumed a higher-SFA/lower-UFA diet for 4 wk, followed by an isoenergetic, lower-SFA/higher-UFA diet for 4 wk (achieved intakes SFA:UFA as % total energy 19.1:14.8 and 8.9:24.5, respectively). Serum LDL cholesterol, CVD risk markers, peripheral blood mononuclear cell (PBMC) gene expression, and dietary intakes were assessed at baseline and the end of each diet. ResultsTransition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet significantly reduced fasting blood lipids: LDL cholesterol (−0.50 mmol/L; 95% confidence interval [CI]: −0.58, −0.42), high-density lipoprotein (HDL) cholesterol (−0.11 mmol/L; 95% CI: −0.14, −0.08), and total cholesterol (TC) (−0.65 mmol/L; 95% CI:−0.75, −0.55). The dietary exchange also reduced apolipoprotein (apo)B, TC:HDL cholesterol ratio, non-HDL cholesterol, E-selectin (P < 0.0001), and LDL subfraction composition (cholesterol [LDL-I and LDL-II], apoB100 [LDL-I and LDL-II], and TAG [LDL-II]) (P < 0.01). There was also an increase in plasma biomarkers of cholesterol intestinal absorption (β-sitosterol, campesterol, cholestanol), and synthesis (desmosterol) (P < 0.0001) and fold change in PBMC LDL-receptor mRNA expression relative to the higher-SFA/lower-UFA diet (P = 0.035). Marked interindividual variation in the change in serum LDL cholesterol response (−1.39 to +0.77 mmol/L) to this dietary exchange was observed, with 33.7% of this variation explained by serum LDL cholesterol before the lower-SFA/higher-UFA diet and reduction in dietary SFA intake (adjusted R2 27% and 6.7%, respectively). APOE genotype was unrelated to serum LDL cholesterol response to SFA. ConclusionsThese findings support the efficacy of United Kingdom SFA dietary guidelines for the overall lowering of serum LDL cholesterol but showed marked variation in LDL cholesterol response. Further identification of the determinants of this variation will facilitate targeting and increasing the efficacy of these guidelines.The RISSCI-1 study was registered with ClinicalTrials.Gov (No. NCT03270527).

Dietary Milk Phospholipids Increase Body Fat and Modulate Gut Permeability, Systemic Inflammation, and Lipid Metabolism in Mice

The study aimed at how dietary milk polar lipids affect gut permeability, systemic inflammation, and lipid metabolism during diet-induced obesity (DIO). C57BL/6J mice (n = 6x3) were fed diets with 34% fat as energy for 15 weeks: (1) modified AIN-93G diet (CO); (2) CO with milk gangliosides (GG); (3) CO with milk phospholipids (MPL). Gut permeability was assessed by FITC-dextran and sugar absorption tests. Intestinal tight junction proteins were evaluated by Western blot. Plasma cytokines were measured by immunoassay. Body composition was assessed by magnetic resonance imaging. Tissue lipid profiles were obtained by thin layer chromatography. Hepatic expression of genes associated with lipid metabolism was assessed by RT-qPCR. MPL increased the efficiency of converting food into body fat and facilitated body fat accumulation compared with CO. MPL and GG did not affect fasting glucose or HOMA-IR during DIO. MPL increased while GG decreased plasma TG compared with CO. MPL decreased phospholipids subclasses in the muscle while increased those in the liver compared with CO. GG and MPL had little effect on hepatic expression of genes associated with lipid metabolism. Compared with CO, MPL decreased polar lipids content in colon mucosa. Small intestinal permeability decreased while colon permeability increased and then recovered during the feeding period. High-fat feeding increased plasma endotoxin after DIO but did not affect plasma cytokines. MPL and GG did not affect plasma endotoxin, adipokines and inflammatory cytokines. After the establishment of obesity, MPL increased gut permeability to large molecules but decreased intestinal absorption of small molecules while GG tended to have the opposite effects. MPL and GG decreased mannitol and sucralose excretions, which peaked at d 45 in the CO group. MPL decreased occludin in jejunum mucosa compared with CO. GG and MPL did not affect zonula occludens-1 in gut mucosa. In conclusion, during DIO, milk GG decreased gut permeability, and had little effect on systemic inflammation and lipid metabolism; MPL facilitated body fat accumulation, decreased gut permeability, did not affect systemic inflammation.

Comparative pharmacokinetic investigation on crocetin in hyperlipidemia and normal rats after oral administration.

Crocetin as one of the main components of saffron possesses a lot of pharmacological effects, especially the beneficial effects in the treatment of hyperlipidemia. However, the pharmacokinetics of crocetin in the pathological state of hyperlipidemia has not been reported. In present study, the pharmacokinetics of crocetin in hyperlipidemia rats after oral administration of crocetin was investigated and the possible mechanisms for the pharmacokinetics were explored. High-fat diet was used to induce hyperlipidemia in rats. The pharmacokinetics of crocetin was investigated in hyperlipidemia and normal rats after oral and intravenous administration of crocetin, and the possible mechanisms of the pharmacokinetic changes were investigated in terms of metabolism and absorption using in vitro incubation with liver microsomes and the everted gut sac method, respectively. Results indicated that the AUCs of crocetin in hyperlipidemia rats after oral administration of crocetin were remarkably decreased when compared with those in normal rats. Moreover, crocetin was also metabolized more rapidly in the liver microsomes of hyperlipidemia rats and intestinal absorption of crocetin was significantly reduced in hyperlipidemia rats. It suggested that the remarkably decreased AUCs of crocetin in hyperlipidemia rats might partly result from the result of faster metabolic elimination and reduced absorption of crocetin in the hyperlipidemia pathological state. And the present investigations conducted on rats demonstrate that further investigations into the kinetics of crocetin in humans with hyperlipidemia are necessary in order to ensure an adequate dosage in this indication.

Determination of 13 perfluorinated and polyfluoroalkyl substances in fishes by QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry

Perfluorinated and polyfluoroalkyl substances (PFASs) are compounds characterized by at least one perfluorinated carbon atom in an alkyl chain linked to side-chain groups. Owing to their unique chemical properties, these compounds are widely used in industrial production and daily life. However, owing to anthropogenic activities, sewage discharge, surface runoff, and atmospheric deposition, PFASs have gradually infiltrated the environment and aquatic resources. With their gradual accumulation in environmental waters, PFASs have been detected in fishes and several fish-feeding species, suggesting that they are bioconcentrated and even amplified in aquatic organisms. PFASs exhibit high intestinal absorption efficiencies, and they bioaccumulate at higher trophic levels in the food chain. They can be bioconcentrated in the human body via food (e. g., fish) and thus threaten human health. Therefore, establishing an efficient analytical technique for use in analyzing PFASs in typical fish samples and providing technical support for the safety regulation and risk assessment of fish products is necessary. In this study, by combining solvent extraction and magnetic dispersion-solid phase extraction (d-SPE), an improved QuEChERS method with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the determination of 13 PFASs in fish samples. Fe3O4-TiO2 can be used as an ideal adsorbent in the removal of sample matrix interference and a separation medium for the rapid encapsulation of other solids to be isolated from the solution. Based on the matrix characteristics of the fish products and structural properties of the target PFASs, Fe3O4-TiO2 and N-propyl ethylenediamine (PSA) were employed as adsorbents in dispersive purification. The internal standard method was used in the quantitative analyses of the PFASs. To optimize the sample pretreatment conditions of analyzing PFASs, the selection of the extraction solvent and amounts of Fe3O4-TiO2 and PSA were optimized. Several PFASs contain acidic groups that are non-dissociated in acidic environments, thus favoring their entry into the organic phase. In addition, acidified acetonitrile can denature and precipitate the proteins within the sample matrix, facilitating their removal. Finally, 2% formic acid acetonitrile was used as the extraction solvent, and 20 mg Fe3O4-TiO2, 20 mg PSA and 120 mg anhydrous MgSO4 were used as purification adsorbents. Under the optimized conditions, the developed method exhibited an excellent linearity (R≥0.9973) in the range of 0.01-50 μg/L, and the limits of detection (LODs) and quantification (LOQs) ranged from 0.001-0.023 and 0.003-0.078 μg/L, respectively. The recoveries of the 13 PFASs at low, medium, and high spiked levels (0.5, 10, and 100 μg/kg) were 78.1%-118%, with the intra- and inter-day precisions of 0.2%-11.1% and 0.8%-8.7%, respectively. This method was applied in analyzing real samples, and PFASs including perfluorooctanesulfonic acid, perfluorooctanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotridecanoic acid, were detected in all 11 samples evaluated. This method is simple, sensitive, and suitable for use in analyzing PFASs in fish samples.

Growth performance, mucosal immunity and disease resistance in goldfish (Carassius auratus) orally administered with Escherichia coli Strain Nissle 1917.

The current research aimed to shed light on the efficacy of Escherichia coli strain Nissle 1917 (EcN) on goldfish (……) growth, gut immunity, morphology, bacterial nutritional enzyme activity and resistance to Aeromonas hydrophila infection. Fish fed with EcN at 106, 107 and 108CFU/g feed for 80days showed an enhancement in growth better than control fish. The gut innate immunity in terms of lysozyme activity, immunoglobulin and total protein levels was increased in the treatment fish with the best result being observed in fish fed EcN at 108CFU/ g. In addition, an increase was noted in the upregulation of immune-relevant genes, namely lysozyme, interleukin-1β, inducible nitric oxide synthase and tumor necrosis factor α of fish intestine. A marked surge in the number of proteolytic and heterotrophic bacteria was noted in the gut of fish nourished with the probiotic. Histological studies exhibited an improvement in the intestinal absorption surface area, intraepithelial lymphocyte count and goblet cell density. Significantly higher survival rate was obtained in fish fed EcN at 108CFU/g compared with the fish fed with the basal diet. These data exhibited the beneficial effect of EcN on goldfish growth, digestive enzymes, intestine heterotrophic bacteria and resistance against Aeromonas hydrophila challenge. This study confirmed the favorable outcomes resulting from the administration of EcN at108 CFU/g.

Identification, screening and molecular mechanisms of natural stable angiotensin-converting enzyme (ACE) inhibitory peptides from foxtail millet protein hydrolysates: a combined in silico and in vitro study.

The stability of bioactive peptides under various food processing conditions is the basis for their use in industrial manufacturing. This study aimed to identify natural ACE inhibitors with excellent stability and investigate their physicochemical properties and putative molecular mechanisms. Five novel ACE inhibitory peptides (QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ) were isolated and identified using RP-HPLC and Nano LC-MS/MS with foxtail millet protein hydrolysates as the raw material. These peptides are non-toxic and exhibit strong ACE inhibitory activity in vitro (IC50 values between 0.13 mg mL-1 and 0.56 mg mL-1). In addition to QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ have excellent human intestinal absorption. Compared to FPGVSPF and SPAQLLPF, the stable helical structure of LVPYRP and WYWPQ allows them to maintain high stability under conditions that mimic gastrointestinal digestion and various food processing (temperatures, pH, sucrose, NaCl, citric acid, sodium benzoate, Cu2+, Zn2+, K+, Mg2+, Ca2+). The results of molecular docking and molecular dynamics simulation suggest that LVPYRP has greater stability and binding capacity to ACE than WYWPQ. LVPYRP might attach to the active pockets (S1, S2, and S1') of ACE via hydrogen bonds and hydrophobic interactions, then compete with Zn2+ in ACE to demonstrate its ACE inhibitory activity. The binding of LVPYRP to ACE enhances the rearrangement of ACE's active structural domains, with electrostatic and polar solvation energy contributing the most energy to the binding. Our findings suggested that LVPYRP derived from foxtail millet protein hydrolysates has the potential to be incorporated into functional foods to provide antihypertensive benefits.

Intestinal microbial and metabolite profile in infants with small bowel stomas after bowel resection.

Infants with small bowel stomas (SBstoma) frequently struggle with absorption and rely on parenteral nutrition (PN). Intestinal absorption is difficult to predict based solely on intestinal anatomy. The purpose of this study was to characterize the microbiota and metabolic by-products within stoma effluent and correlate with clinical features and intestinal absorption. Prospective cohort study collecting stoma samples from neonates with SBstoma (N = 23) or colostomy control (N = 6) at initial enteral feed (first sample) and before stoma closure (last sample). Gut bacteriome (16S ribosomal RNA [rRNA] sequencing), short-chain fatty acids (SCFAs) and bile acids (BAs) were characterized along with volume and energy content of a 48 h collection via bomb calorimetry (last sample). Hierarchical clustering and linear regression were used to compare the bacteriome and BAs/SCFAs, to bowel length, PN, and growth. Infants with ≤50% small bowel lost more fluid on average than those with >50% and controls (22, 18, 16 mL/kg/day, p = 0.013), but had similar energy losses (7, 10, 9 kcal/kg/day, p = 0.147). Infants growing poorly had enrichment of Proteobacteria compared to infants growing well (90% vs. 15%, p = 0.004). An increase in the ratio of secondary BAs within the small bowel over time, correlated with poor prognostic factors (≤50% small bowel, >50% of calories from PN, and poor growth). Infants with SBstoma and poor growth have a unique bacteriome community and those with poor enteral tolerance have metabolic differences compared to infants with improved absorption.

Intestinal Absorption Site-Guided Development and Evaluation of Oral Disintegrating Controlled Release Tablets of Mirabegron

The aim was to employ site-dependent absorption of mirabegron (MB) as a guide for fabrication of oral disintegrating controlled release tablet (ODCRT) which undergoes instantaneous release of loading fraction followed by delayed release of the rest of MB. The goal was to release MB in a manner consistent with the chronobiology of overactive bladder (OAB) syndrome. In situ rabbit intestinal permeability of MB was adopted to assess absorption sites. MB was subjected to dry co-grinding with citric acid to develop the fast-dissolving fraction in the mouth. Delayed release fraction was formulated by ethanol-assisted co-processing with increasing proportions of Eudragit polymer (S100) as pH responsive polymer. The developed dry mixtures underwent thermal (DSC) and physical (X-ray diffraction) characterization, in addition to in vitro release behavior. Optimized fast dissolving and delayed release formulations were mixed with tablet excipient before compression in ODCRT which was assessed for release profile using continuous pH variation. MB underwent preferential permeation through ileum and colon. Co-grinding with citric acid provided co-amorphous powder with fast dissolution. Co-amorphization of MB with Eudragit S100 (1:5) showed pH-dependent release to release most of the dose at pH 7.4. The developed ODCRT released 43.5% of MB in the buccal environment and retained MB at acidic pH to start release at pH 7.4. The study successfully fabricated ODCRT guided by site-dependent absorption. The ODCRT instantaneously released loading fraction to support the patient after administration with delayed fraction to sustain the effect.Graphical

The synergistic effect of Huangqi Gegen decoction on thrombosis relates to the astragalus polysaccharide-improved oral delivery of puerarin

Ethno-pharmacological relevanceHuangqi Gegen decoction (HGD), which comprises Astragali Radix (AR) and Puerariae Radix (PR), is widely used to treat thrombosis in China. However, the mechanism underlying its synergistic effect in thrombosis treatment remains unclear. Aim of the studyFollowing PR administration, low plasma exposure was reported for its primary ingredients. In this regard, this study examined the effect of AR on PR's antithrombotic efficacy with respect to the impact of Astragalus Polysaccharide (APS) on the oral delivery of Puerarin (PUE). Materials and methodsTo evaluate the synergistic effect of HGD, a thrombus mice model was established via intraperitoneal injection of carrageenan. After treatment, histopathological observations were made, and the proportion of thrombus length in the tail, as well as the plasma APTT, PT, INR, and FIB levels, were detected. Molecular docking was employed to assess the PR ingredients that could inhibit the HMGB1/NF-κB/NLRP3 pathway. The Pharmacokinetics of PR ingredients in rats were also compared between the PR and HGD groups. Moreover, the effect of APS on the solubility, intestinal absorption, and pharmacokinetics of PUE was evaluated. Furthermore, the impact of APS on the antithrombotic efficacy of PUE was assessed. ResultsIn mice, AR enhanced the antithrombotic effect of PR. This improved PR effect was associated with isoflavones-induced downregulation of the HMGB1/NF-κB/NLRP3 pathway. The synergistic effect resulting from the compatibility of HGD components was primarily achieved by improving the plasma exposure of PR isoflavones. Specifically, APS enhanced PUE's water solubility through the formation of self-assembly Nanoparticles, increasing its intestinal absorption and oral bioavailability, which, in turn, suppressed the HMGB1/NF-κB/NLRP3 pathway, thus improving its antithrombotic effect. ConclusionsOur findings revealed that APS improved PUE's plasma exposure, enhancing its inhibitory effect on the HMGB1/NF-κB/NLRP3 pathway. This mechanism presents a key aspect of the synergistic effect of HGD compatibility in thrombosis treatment.

Exploring the synergistic effects of chuanxiong rhizoma and Cyperi rhizoma in eliciting a rapid anti-migraine action based on pharmacodynamics and pharmacokinetics

Ethnopharmacological relevanceHerb-herb combination has been used to maximize the therapeutic efficacy in the theory of traditional Chinese medicine. Chuanxiong rhizoma (called Chuanxiong in Chinese, CX) and Cyperi rhizoma (called Xiangfu in Chinese, XF) have been used alone or in combination (CRCR) to treat migraine dating back to Eastern Jin Dynasty (AD317) of China. But no data demonstrate the possible necessities or advantages of combining CX and XF for migraine. Aim of the studyThis study explores the combination mechanism based on pharmacodynamics and pharmacokinetics. Materials and methodsA nitroglycerin-induced acute migraine model in rats was used to evaluate the anti-migraine effects of CRCR and the individual herbs using behavior, real time polymerase chain reaction and Western blot experiments. The absorption characteristics of active components involved in the anti-migraine action were analyzed by UPLC-MS/MS. ResultsCX and CRCR significantly reversed the abnormal levels of vasoactive substances (5-HT, CGRP, MMP-2 and MMP-9) to normal levels, but XF did not. XF and CRCR significantly decreased the pro-inflammatory cytokines (IL-1β, IL-6, and TNF-a), and increased the anti-inflammatory cytokines (IL-4 and IL-10). CRCR significantly decreased the mRNA expression levels of c-fos, iNos and nNos, and the corresponding protein expression levels of c-Fos, iNOS, and nNOS. CRCR inhibited NOS/NO pathway by downregulating the expression levels of NOS and NO. Furthermore, CRCR significantly increased the intestinal absorption rate and amount, and changed the pharmacokinetic parameters of active components in comparison with the individual herbs. ConclusionsCX had an advantage in regulating vasoactive substances, and XF focused on regulating inflammatory cytokines. CRCR is more effective in treating migraine than the individual herbs by depending on the synergistic action of CX and XF. This research provided some critical evidences on synergistic action between herb-herb interactions, and revealed the potential advantages of herb-herb combination in traditional Chinese medicine.

Evaluating intestinal absorption of peptide Met-Lys-Pro in casein hydrolysate using Caco-2 and human iPS cell-derived small intestinal epithelial cells

High blood pressure is a major risk factor for cardiovascular disease. Our previous study confirmed that daily intake of casein hydrolysate that contained Met-Lys-Pro (MKP) can safely lower mildly elevated blood pressure. The present study aimed to evaluate the intestinal absorption differences between peptide MKP as a casein hydrolysate and synthetic MKP alone using Caco-2 cells and human iPS cell-derived small intestinal epithelial cells (hiSIECs). MKP was transported intact through Caco-2 cells and hiSIECs with permeability coefficient (Papp) values of 0.57 ± 0.14 × 10-7 and 1.03 ± 0.44 × 10-7 cm/s, respectively. This difference in Papp suggests differences in the tight junction strength and peptidase activity of each cell. Moreover, the transepithelial transport and residual ratio of intact MKP after adding casein hydrolysate containing MKP was significantly higher than that after adding synthetic MKP alone, suggesting that other peptides in casein hydrolysate suppressed MKP degradation and increased its transport. These findings suggest that hiSIECs could be useful for predicting the human intestinal absorption of bioactive peptides; ingesting MKP as a casein hydrolysate may also improve MKP bioavailability.

Elemental Profiling of Common Anti-diabetic Medicinal Plants of Swat and Peshawar Districts of Khyber Pakhtunkhwa (KPK) Province of Pakistan: An Investigation Using PIXE and ICP-OES.

The use of medicinal plants is integral to addressing liver, heart, lung, and other metabolic issues. These plants are rich in vitamins, minerals, flavonoids, and alkaloids, which collectively help in lowering intestinal glucose absorption and increasing insulin secretion by pancreatic tissues. Elemental analysis, encompassing major, minor, and trace elements, was performed on various parts (leaves, roots, and seeds) of 16 anti-diabetic medicinal plants collected from different regions of Swat and Peshawar in Khyber Pakhtunkhwa (KPK), Pakistan. This analysis utilized proton-induced X-ray emission (PIXE) and inductively coupled plasma optical emission spectroscopy (ICP-OES) techniques. Our PIXE and ICP-OES analysis revealed the presence of major (Ca, K, S, P), minor (Si, Cl), and trace (Al, Mn, Fe, Ni, Cu, Zn, Se, Cr, and Sc) elements in various parts (leaves, roots, and seeds) of the 16 anti-diabetic medicinal plants studied. Specifically, elements such as Ca, K, Cr, Cu, Mn, Zn, and Se were detected, all of which are known to contribute in maintaining normal glucose metabolism. Notably, Zn and Se are crucial trace elements for the synthesis, secretion, and action of insulin. Significant Zn concentrations were observed in ten anti-diabetic medicinal plants: Albizia lebbeck (AL), Atropa acuminata (AA), Avena fatua (AF), Citrus medica (CM), Commiphora wightii (CW), Cymbopogon citratus (CC), Daucus carota (DC), Ziziphus mauritiana (FM), Hyoscyamus niger (HN), and Martynia annua (MA), and significant Se concentrations were observed in twelve medicinal plants, i.e., Albizia lebbeck (AL), Allium sativum (AS), Atropa acuminata (AA), Avena fatua (AF), Cannabis sativa (CS), Capparis spinosa (CaS), Commiphora wightii (CW), Cymbopogon citratus (CC), Datura alba (DA), Daucus carota (DC), Ziziphus mauritiana (FM), and Hyoscyamus niger (HN). Our study's elemental analysis using PIXE and ICP-OES on various parts of 16 medicinal plants identified a significant number of useful elements. Elements such as Ca, K, S, P, Al, Si, Cl, Mn, Fe, Ni, Cu, Zn, Se, and Cr were identified and quantified. These findings support the potential use of these plants in managing diabetes and highlight the importance of elemental profiling in understanding their therapeutic properties.

Comparison of intestinal absorption of soybean protein isolate-, glutenin- and peanut protein isolate-bound Nε-(carboxymethyl) lysine after in vitro gastrointestinal digestion

Advanced glycation end products (AGEs), a heterogeneous compound existed in processed foods, are related to chronic diseases when they are accumulated excessively in human organs. Protein-bound Nε-(carboxymethyl) lysine (CML) as a typical AGE, is widely determined to evaluate AGEs level in foods and in vivo. This study investigated the intestinal absorption of three protein-bound CML originated from main food raw materials (soybean, wheat and peanut). After in vitro gastrointestinal digestion, the three protein-bound CML digests were ultrafiltered and divided into four fractions: less than 1 kDa, between 1 and 3 kDa, between 3 and 5 kDa, greater than 5 kDa. Caco-2 cell monolayer model was further used to evaluate the intestinal absorption of these components. Results showed that the absorption rates of soybean protein isolate (SPI)-, glutenin (Glu)-, peanut protein isolate (PPI)-bound CML were 30.18%, 31.57% and 29.5%, respectively. The absorption rates of components with MW less than 5 kDa accounted for 19.91% (SPI-bound CML), 22.59% (Glu-bound CML), 23.64% (PPI-bound CML), respectively, and these samples were absorbed by paracellular route, transcytosis route and active route via PepT-1. Taken together, these findings demonstrated that all three protein-bound CML digests with different MW can be absorbed in diverse absorption pathways by Caco-2 cell monolayer model. This research provided a theoretical basis for scientific evaluation of digestion and absorption of AGEs in food.

Structure-dependent capacity of procyanidin dimers to inhibit inflammation-induced barrier dysfunction in a cell model of intestinal epithelium

Diet is of major importance in modulating intestinal inflammation, as the gastrointestinal tract is directly exposed to high concentrations of dietary components. Procyanidins are flavan-3-ol oligomers abundant in fruits and vegetables. Although with limited or no intestinal absorption, they can have GI health benefits which can promote overall health. We previously observed that epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) dimers inhibit in vitro colorectal cancer cell proliferation and invasiveness. Inflammation-mediated intestinal barrier permeabilization can result in a chronic inflammatory condition and promote colorectal cancer onset/progression. Thus, this study investigated the structure-dependent capacity of ECG, EGCG and (−)-epicatechin (EC) dimers to inhibit tumor necrosis factor alpha (TNFα)-induced inflammation, oxidative stress, and loss of barrier integrity in Caco-2 cells differentiated into an intestinal epithelial cell monolayer. Cells were incubated with TNFα (10 ng/ml), in the absence/presence of ECG, EGCG and EC dimers. The three dimers inhibited TNFα-mediated Caco-2 cell monolayer permeabilization, modulating events involved in the loss of barrier function and inflammation, i.e. decreased tight junction protein levels; increased matrix metalloproteinases expression and activity; increased NADPH oxidase expression and oxidant production; activation of the NF-κB and ERK1/2 pathways and downstream events leading to tight junction opening. For some of these mechanisms, the galloylated ECG and EGCG dimers had stronger protective potency than the non-galloylated EC dimer. These differences could be due to differential membrane interactions as pointed out by molecular dynamics simulation of procyanidin dimers-cell membrane interactions and/or by differential interactions with NOX1. Results show that dimeric procyanidins, although poorly absorbed, can promote health by alleviating intestinal inflammation, oxidative stress and barrier permeabilization.

Assessing the Protein Quality, In Vitro Intestinal Iron Absorption and Human Faecal Microbiota Impacts of Plant-Based Mince.

The nutritional quality of plant-based meat analogues compared to traditional meat products has been questioned in recent commentary, particularly in relation to protein quality and micronutrient bioavailability. However, the attributes of specific products within this category are unclear. We therefore undertook a comprehensive assessment of the compositional and functional attributes of v2food® (Sydney, Australia) plant-based mince, including an assessment of the effects of reformulation, including the addition of amino acids, ascorbic acid, and different forms of elemental iron. The protein digestibility and protein quality of v2food® plant-based mince were comparable to beef mince in the standardized INFOGEST system, and favourable effects on microbiota composition and short-chain fatty acid (SCFA) production were demonstrated in an in vitro digestion system. The use of ferrous sulphate as an iron source improved in vitro intestinal iron absorption by ~50% in comparison to other forms of iron (p < 0.05), although levels were ~3-fold lower than beef mince, even in the presence of ascorbic acid. In conclusion, the current study identified some favourable nutritional attributes of plant-based v2food® mince, specifically microbiota and SCFA changes, as well as other areas where further reformulation could be considered to further enhance the bioavailability of key nutrients. Further studies to assess the effect of plant-based meat analogues on health measures in vivo will be important to improve knowledge in this area.

Platycodon D reduces obesity and non-alcoholic fatty liver disease induced by a high-fat diet through inhibiting intestinal fat absorption.

Platycodin D (PD) has been reported to treat metabolic diseases, including non-alcoholic fatty liver disease. In addition, platycodin D has been reported to activate intestinal 5'AMP-activated protein kinase (AMPK) phosphorylation levels, thereby reducing lipid absorption. Therefore, the aim of this study is to explore whether PD activation of intestinal AMPK and reduced lipid absorption can improve non-alcoholic fatty liver disease. Clean-grade male C57/BL mice were fed a high-fat diet (HFD) (containing 60% calories) for 16 weeks, and oral PD (10mg/kg/day) was administered at the same time. The liver and intestines were the collected, and the intestines were tested. The expressions of lipid absorption genes (CD36, NPC1L1, and ApoB), the serum total triglyceride (TG) and total cholesterol (TC) levels in the intestines and livers, the fecal free fatty acid (FFA) levels, and the expression of AMPK phosphorylated proteins in the intestines were examined using Western blot analyses. The lipid distribution in the livers, intestines, and fat was detected using Oil Red O and hematoxylin and eosin (H&E) staining. A colon cancer cell line (Caco2) was used to confirm the effect of PD on the cellular lipid uptake in vitro. In addition, serum inflammatory factors and liver enzymes were measured to clarify the impact of PD on the circulation of metabolic syndrome. Leptin-deficient mice (OB) were then used to further explore the improvement of PD on body weight and blood lipids. PD had a very significant therapeutic or preventive effect on metabolic syndrome and fatty liver induced by a high-fat diet. PD improved body weight, insulin sensitivity, and glucose tolerance in mice fed a high-fat diet and also prevented non-alcoholic fatty liver disease, reduced blood lipid levels, and increased fecal lipid excretion. In addition, PD reduced lipid absorption by activating the intestinal AMPK protein, which may have involved the inhibition of the gene expression levels of intestinal lipid absorption genes (CD36, NPC1L1, and ApoB). The combined effect of these factors improved hepatic lipid accumulation and lipid accumulation in adipose tissue. It was further found that PD also improved the body weights and blood lipid levels of leptin-deficient mice (OB) mice. PD had a very strong therapeutic effect on mice under a high-fat diet. PD reduced high-fat diet-induced obesity and non-alcoholic fatty liver disease by inhibiting intestinal fat absorption.

Effects of Hermetia illucens larvae meal and astaxanthin on intestinal histology and expression of tight junction proteins in weaned piglets.

The weaning phase in piglets causes significant physiological stress, disrupts intestinal integrity and reduces productivity, necessitating strategies to improve intestinal health and nutrient absorption. While current research highlights the role of diet in mitigating these adverse effects, identifying effective dietary supplements remains a challenge. This study evaluated the effects of Hermetia illucens (HI) larvae meal and astaxanthin (AST) on the intestinal histology of weaned piglets. In a controlled experiment, 48 weaned piglets were divided into six groups and received varying levels of HI larval meal (2.5% and 5%) and AST in their diets. The methodology involved comprehensive histological examinations of the small intestine, assessing absorption area, villi elongation, crypt depth, goblet cells, enterocytes and expression of ileal tight junction (TJ) proteins. The study found that HI larval meal significantly improved nutrient absorption in the jejunum and ileum (p < 0.001), thereby enhancing feed conversion. AST supplementation increased the number of enterocytes (p < 0.001). Both HI larval meal and AST positively affected intestinal morphology and function, increasing muscularis muscle mass and villi elongation (p < 0.001 and p < 0.05, respectively). The 2.5% HI meal improved the villi length to crypt depth ratio and slightly increased the goblet cell count (both p < 0.05). Ki-67 antibody analysis showed increased cell proliferation in the duodenal and jejunal crypts, particularly with the 2.5% HI meal (p < 0.001). Insect meal did not affect TJ protein expression, indicating that it had no effect on intestinal permeability. These findings suggest that HI larval meal and AST can enhance the intestinal wellness and productivity of weaned piglets.

GSDME promotes MASLD by regulating pyroptosis, Drp1 citrullination-dependent mitochondrial dynamic, and energy balance in intestine and liver.

Dysregulated metabolism, cell death, and inflammation contribute to the development of metabolic dysfunction-associated steatohepatitis (MASH). Pyroptosis, a recently identified form of programmed cell death, is closely linked to inflammation. However, the precise role of pyroptosis, particularly gasdermin-E (GSDME), in MASH development remains unknown. In this study, we observed GSDME cleavage and GSDME-associated interleukin-1β (IL-1β)/IL-18 induction in liver tissues of MASH patients and MASH mouse models induced by a choline-deficient high-fat diet (CDHFD) or a high-fat/high-cholesterol diet (HFHC). Compared with wild-type mice, global GSDME knockout mice exhibited reduced liver steatosis, steatohepatitis, fibrosis, endoplasmic reticulum stress, lipotoxicity and mitochondrial dysfunction in CDHFD- or HFHC-induced MASH models. Moreover, GSDME knockout resulted in increased energy expenditure, inhibited intestinal nutrient absorption, and reduced body weight. In the mice with GSDME deficiency, reintroduction of GSDME in myeloid cells-rather than hepatocytes-mimicked the MASH pathologies and metabolic dysfunctions, as well as the changes in the formation of neutrophil extracellular traps and hepatic macrophage/monocyte subclusters. These subclusters included shifts in Tim4+ or CD163+ resident Kupffer cells, Ly6Chi pro-inflammatory monocytes, and Ly6CloCCR2loCX3CR1hi patrolling monocytes. Integrated analyses of RNA sequencing and quantitative proteomics revealed a significant GSDME-dependent reduction in citrullination at the arginine-114 (R114) site of dynamin-related protein 1 (Drp1) during MASH. Mutation of Drp1 at R114 reduced its stability, impaired its ability to redistribute to mitochondria and regulate mitophagy, and ultimately promoted its degradation under MASH stress. GSDME deficiency reversed the de-citrullination of Drp1R114, preserved Drp1 stability, and enhanced mitochondrial function. Our study highlights the role of GSDME in promoting MASH through regulating pyroptosis, Drp1 citrullination-dependent mitochondrial function, and energy balance in the intestine and liver, and suggests that GSDME may be a potential therapeutic target for managing MASH.