The water extracts from the oil cakes of Prinsepia utilis repair the epidermal barrier via up-regulating Corneocyte Envelope-proteins, lipid synthases, and tight junction proteins.

ETHNOPHARMACOLOGICAL RELEVANCE: Prinsepia utilis Royle, native to the Himalayan region, has a long history of use in traditional medicine for its heat-clearing, detoxification, anti-inflammatory, and analgesic properties. Oils extracted from P. utilis seeds are also used in cooking and cosmetics. With the increasing market demand, this extraction process generates substantial industrial biowastes. Recent studies have found many health benefits with using aqueous extracts of these biowastes, which are also rich in polysaccharides. However, there is limited research related to the reparative effects of the water extracts of P. utilis oil cakes (WEPUOC) on disruptions of the skin barrier function. AIM OF THE STUDY: This study aimed to evaluate the reparative efficacy of WEPUOC in both acute and chronic epidermal permeability barrier disruptions. Furthermore, the study sought to explore the underlying mechanisms involved in repairing the epidermal permeability barrier. MATERIALS AND METHODS: Mouse models with induced epidermal disruptions, employing tape-stripping (TS) and acetone wiping (AC) methods, were used. The subsequent application of WEPUOC (100 mg/mL) was evaluated through various assessments, with a focus on the upregulation of mRNA and protein expression of Corneocyte Envelope (CE) related proteins, lipid synthase-associated proteins, and tight junction proteins. RESULTS: The polysaccharide was the major phytochemicals of WEPUOC and its content was determined as 32.2% by the anthranone-sulfuric acid colorimetric method. WEPUOC significantly reduced transepidermal water loss (TEWL) and improved the damaged epidermal barrier in the model group. Mechanistically, these effects were associated with heightened expression levels of key proteins such as FLG (filaggrin), INV (involucrin), LOR (loricrin), SPT, FASN, HMGCR, Claudins-1, Claudins-5, and ZO-1. CONCLUSIONS: WEPUOC, obtained from the oil cakes of P. utilis, is rich in polysaccharides and exhibits pronounced efficacy in repairing disrupted epidermal barriers through increased expression of critical proteins involved in barrier integrity. Our findings underscore the potential of P. utilis wastes in developing natural cosmetic prototypes for the treatment of diseases characterized by damaged skin barriers, including atopic dermatitis and psoriasis.

Multi-omics approach to study the dual effects of novel proteins on the intestinal health of juvenile largemouth bass (Micropterus salmoides) under an alternate feeding strategy.

Introduction: In an effort to minimize the usage of fishmeal in aquaculture, novel protein diets, including Tenebrio molitor, cottonseed protein concentrate, Clostridium autoethanogenum, and Chlorella vulgaris were evaluated for their potential to replace fishmeal. Nevertheless, comprehensive examinations on the gut health of aquatic animals under an alternate feeding strategy when fed novel protein diets are vacant. Methods: Five isonitrogenous and isolipidic diets containing various proteins were manufactured, with a diet consisting of whole fishmeal serving as the control and diets containing novel proteins serving as the experimental diets. Largemouth bass (Micropterus salmoides) with an initial body weight of 4.73 ± 0.04g employed as an experimental animal and given these five diets for the first 29 days followed by a fishmeal diet for the next 29 days. Results: The results of this study demonstrated that the growth performance of novel protein diets in the second stage was better than in the first stage, even though only the C. vulgaris diet increased antioxidant capacity and the cottonseed protein concentrate diet decreased it. Concerning the intestinal barriers, the C. autoethanogenum diet lowered intestinal permeability and plasma IL-1ß/TNF-α. In addition, the contents of intestinal immunological factors, namely LYS and sIgA-like, were greater in C. vulgaris than in fishmeal. From the data analysis of microbiome and metabolome, the levels of short chain fatty acids (SCFAs), anaerobic bacteria, Lactococcus, and Firmicutes were significantly higher in the C. autoethanogenum diet than in the whole fishmeal diet, while the abundance of Pseudomonas, aerobic bacteria, Streptococcus, and Proteobacteria was lowest. However, no extremely large differences in microbiota or short chain fatty acids were observed between the other novel protein diets and the whole fishmeal diet. In addition, the microbiota were strongly connected with intestinal SCFAs, lipase activity, and tight junctions, as shown by the Mantel test and Pearson's correlation. Discussion: Taken together, according to Z-score, the ranking of advantageous functions among these protein diets was C. autoethanogenum diet > C. vulgaris diet > whole fishmeal diet > cottonseed protein concentrate > T. molitor diet. This study provides comprehensive data illustrating a mixed blessing effect of novel protein diets on the gut health of juvenile largemouth bass under an alternate feeding strategy.

Effect and Mechanisms of Quercetin for Experimental Focal Cerebral Ischemia: A Systematic Review and Meta-Analysis.

Quercetin, a naturally occurring flavonoid, is mainly extracted from tea, onions, and apples. It has the underlying neuroprotective effect on experimental ischemic stroke. A systematic review and meta-analysis were used to assess quercetin's efficacy and possible mechanisms in treating focal cerebral ischemia. Compared with the control group, twelve studies reported a remarkable function of quercetin in improving the neurological function score (NFS) (P < 0.05), and twelve studies reported a significant effect on reducing infarct volume (P < 0.05). Moreover, two and three studies showed that quercetin could alleviate blood-brain barrier (BBB) permeability and brain water content, respectively. The mechanisms of quercetin against focal cerebral ischemia are diverse, involving antioxidation, antiapoptotic, anti-inflammation, and calcium overload reduction. On the whole, the present study suggested that quercetin can exert a protective effect on experimental ischemic stroke. Although the effect size may be overestimated because of the quality of studies and possible publication bias, these results indicated that quercetin might be a promising neuroprotective agent for human ischemic stroke. This study is registered with PROSPERO, number CRD 42021275656.

Protection against indomethacin-induced loss of intestinal epithelial barrier function by a quercetin oxidation metabolite present in onion peel: In vitro and in vivo studies.

Oxidative stress is directly implicated in the loss of intestinal epithelial barrier function (IEBF) induced by non-steroidal anti-inflammatory drugs (NSAIDs). Previous studies by our research team demonstrated that 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (BZF), a quercetin oxidation metabolite that naturally occurs in onion peels, exhibits an antioxidant potency notably higher than quercetin. Thus, we assessed the potential of BZF and a BZF-rich onion peel aqueous extract (OAE) to protect against the loss of IEBF in Caco-2 cell monolayers and in rats exposed to indomethacin. In vitro, pure BZF and OAE standardized in BZF (100 nM), protected against the drop in transepithelial electrical resistance by 70 - 73%. Likewise, it prevented the increase in fluorescein-isothiocyanate labelled dextran (FITC-dextran) paracellular transport by 74% and oxidative stress by 84 - 86%. In vivo, BZF, given orally at a dose 80 µg/Kg bw as OAE, totally abolished a 30-fold increase in FITC-dextran serum concentration induced by indomethacin. This effect was dose-dependent and largely conserved (85%) when OAE was given 180-min prior to indomethacin. The IEBF-protective effect of OAE was accompanied by a full prevention of the NF-ĸB activation, and the increases in interleukine-8 secretion and myeloperoxidase activity induced by indomethacin. The protection was also associated with a 21-fold increase in Nrf2, and a 7-fold and 9-fold increase in heme oxygenase-1 and NAD(P)H-quinone oxidoreductase 1, respectively. The IEBF-protecting effect of OAE involves, most likely, its dual capacity to activate Nrf2 while inhibiting NF-ĸB activation. The extremely low doses of BZF needed to promote such actions warrants extending its IEBF-protective effects to other NSAIDs.

Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice.

Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). An impaired intestinal epithelial barrier is an important component of GVHD pathogenesis. However, contributing host factors that modulate mucosal barrier integrity during GVHD are poorly defined. We hypothesized that vitamin A and retinoic acid (RA) exert positive impacts on maintaining intestinal barrier function after HSCT, thus preventing or dampening GVHD severity. Unexpectedly, we found that exogenous RA increased intestinal permeability of recipient mice after allogeneic HSCT. Serum bacterial endotoxin levels were significantly higher in GVHD mice fed a vitamin A-high (VAH) diet compared to those fed a vitamin A-normal (VAN) diet, indicating a more compromised intestinal barrier function. Furthermore, VAH mice showed more severe lung GVHD with increased donor T cell infiltration in this tissue and died significantly faster than VAN recipients. 16S rRNA sequencing of fecal samples revealed significant differences in the diversity and composition of gut microbiota between VAN and VAH transplant recipients. Collectively, we show that retinoic acid signaling may negatively impact intestinal barrier function during GVHD. Mild vitamin A supplementation is associated with increased lung GVHD and more profound gut dysbiosis. Micronutrients such as vitamin A could modulate complications of allogeneic HSCT, which may be mediated by shaping gut microbiota.

Consumption of Butylated Starch Alleviates the Chronic Restraint Stress-Induced Neurobehavioral and Gut Barrier Deficits Through Reshaping the Gut Microbiota.

The beneficial effect of short-chain fatty acids (SCFAs) on host health has been well recognized based on the booming knowledge from gut microbiome research. The role of SCFA in influencing psychological function is highlighted in recent years but has not been fully elucidated. In this study, the SCFA-acylated starches were used to accomplish a sizeable intestine-targeted release of the SCFAs, and the neurobehavioral, immunological, and microbial effects were further investigated. Acetylated-, butylated-, and isobutylated-starch could attenuate the depression-like behaviors and excessive corticosterone production in chronically stressed mice. Butylated- starch significantly reduced the colonic permeability via increasing the tight junction proteins (including ZO-1, Claudin, and Occludin) gene expression and reduced the level of the inflammatory cytokines (including IL-1ß and IL-6). The butylated starch's neurological and immunological benefits may be derived from the gut microbiome modifications, including normalizing the abundance of certain beneficial microbes (Odoribacter and Oscillibacter) and metabolomic pathways (Tryptophan synthesis and Inositol degradation). The present findings further validate the brain-beneficial effect of butyrate and offer novel guidance for developing novel food or dietary supplements for improving mental health.

Impacts of Fructose on Intestinal Barrier Function, Inflammation and Microbiota in a Piglet Model.

The metabolic disorder caused by excessive fructose intake was reported extensively and often accompanied by intestinal barrier dysfunction. And the rising dietary fructose was consumed at an early age of human. However, related researches were almost conducted in rodent models, while in the anatomy and physiology of gastrointestinal tract, pig is more similar to human beings than rodents. Hence, weaned piglets were chosen as the model animals in our study to investigate the fructose's impacts on intestinal tight junction, inflammation response and microbiota structure of piglets. Herein, growth performance, inflammatory response, oxidation resistance and ileal and colonic microbiota of piglet were detected after 35-day fructose supplementation. Our results showed decreased tight junction gene expressions in piglets after fructose addition, with no obvious changes in the growth performance, antioxidant resistance and inflammatory response. Moreover, fructose supplementation differently modified the microbiota structures in ileum and colon. In ileum, the proportions of Streptococcus and Faecalibacterium were higher in Fru group (fructose supplementation). In colon, the proportions of Blautia and Clostridium sensu stricto 1 were higher in Fru group. All the results suggested that tight junction dysfunction might be an earlier fructose-induced event than inflammatory response and oxidant stress and that altered microbes in ileum and colon might be the potential candidates to alleviate fructose-induced intestinal permeability alteration.

Altered intestinal microflora and barrier injury in severe acute pancreatitis can be changed by zinc.

To investigate the effect of zinc (Zn) supplementation on intestinal microflora changes and bacterial translocation in rats with severe acute pancreatitis (SAP), the rats were divided into the sham surgery (SS), SAP, SS + Zn, and SAP + Zn groups. Saline (0.1 mL/100g) and 5% sodium taurocholate were injected into the pancreaticobiliary duct of the rats in the SS and SAP + Zn groups, respectively. Intraperitoneal injection of 5 mg/kg Zn was performed immediately after injecting saline or 5% sodium taurocholate into the rats in both groups. Serum amylase and Zn levels, plasma endogenous endotoxin, intestinal permeability, and the positive rate of intestinal bacterial translocation were detected, haematoxylin and eosin (H&E) staining was performed, and the pancreatic tissue scores were calculated for each group. In addition, immunohistochemical (IHC) staining was performed to evaluate the expression of IL-1ß and TNF-α. Real-time fluorescence quantitative PCR was used to quantify the gene copy numbers of Escherichia, Bifidobacterium, and Lactobacillus in the cecum. The levels of amylase and plasma endotoxin in the SAP group were significantly higher than those in the SS and SS + Zn groups. Intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were increased in the SAP group. However, the levels of amylase and plasma endotoxin were decreased as a result of zinc supplementation in the SAP group. The expression of IL-1ß and TNF-α was also reduced to a greater degree in the SAP + Zn group than in the SAP group. Moreover, alleviated intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were found in the SAP + Zn group. The results of real-time quantitative PCR showed that the gene copy number of Escherichia increased with time, and the gene copy numbers of Lactobacillus and Bifidobacterium decreased over time. Zn supplementation prevented the release of TNF-α and IL-1ß, alleviated intestinal permeability and endotoxemia, reduced bacterial translocation, and inhibited changes in pathogenic intestinal flora in rats with SAP.

Development and Characterization of Novel Composite Films Based on Soy Protein Isolate and Oilseed Flours.

The possibility of using oilseed flours as a waste source for film-forming materials with a combination of soy protein isolate in preparation of edible films was evaluated. Physical, mechanical and barrier properties were determined as a function of the oilseed type: hemp, evening primrose, flax, pumpkin, sesame and sunflower. It was observed that the addition of oilseed flours increased the refraction and thus the opacity of the obtained films from 1.27 to 9.57 A mm-1. Depending on the type of flours used, the edible films took on various colors. Lightness (L*) was lowest for the evening primrose film (L* = 34.91) and highest for the soy protein film (L* = 91.84). Parameter a* was lowest for the sunflower film (a* = -5.13) and highest for the flax film (a* = 13.62). Edible films made of pumpkin seed flour had the highest value of the b* color parameter (b* = 34.40), while films made of evening primrose flour had the lowest value (b* = 1.35). All analyzed films had relatively low mechanical resistance, with tensile strength from 0.60 to 3.09 MPa. Films made of flour containing the highest amount of protein, pumpkin and sesame, had the highest water vapor permeability, 2.41 and 2.70 × 10-9 g·m-1 s-1 Pa-1, respectively. All the edible films obtained had high water swelling values from 131.10 to 362.16%, and the microstructure of the films changed after adding the flour, from homogeneous and smooth to rough. All blended soy protein isolate-oilseed flour films showed lower thermal stability which was better observed at the first and second stages of thermogravimetric analysis when degradation occurred at lower temperatures. The oilseed flours blended with soy protein isolate show the possibility of using them in the development of biodegradable films which can find practical application in the food industry.

Effects of cannabinoid (CBD) on blood brain barrier permeability after brain injury in rats.

Cannabidiol is a natural herbal medicine known to protect the brain from traumatic brain injury (TBI). Here, a TBI rat model was established, with cannabidiol administered intraperitoneally at doses of 5, 10, or 20 mg/kg, 30 min before surgery and 6 h after surgery until sacrifice. Brain water content, body weight, and modified neurological severity scores were determined, and enzyme-linked immunosorbent assay, immunofluorescence staining, hematoxylin and eosin staining, Nissl staining, Evans-blue dye extravasation, and western blotting were performed. Results showed that cannabidiol decreased the number of aquaporin-4-positive and glial fibrillary acidic protein-positive cells. Cannabidiol also significantly reduced the protein levels of proinflammatory cytokines (TNF-α and IL-1ß) and significantly increased the expression of tight junction proteins (claudin-5 and occludin). Moreover, cannabidiol administration significantly mitigated water content in the brain after TBI and blood-brain barrier disruption and ameliorated the neurological deficit score after TBI. Cannabidiol administration improved the integrity and permeability of the blood-brain barrier and reduced edema in the brain after TBI.

Medicinal Plant Leaf Extract From Sage and Lemon Verbena Promotes Intestinal Immunity and Barrier Function in Gilthead Seabream (Sparus aurata).

The inclusion of a medicinal plant leaf extract (MPLE) from sage (Salvia officinalis) and lemon verbena (Lippia citriodora), rich in verbascoside and triterpenic compounds like ursolic acid, was evaluated in gilthead seabream (Sparus aurata) fed a low fishmeal-based diet (48% crude protein, 17% crude fat, 21.7 MJ kg-1, 7% fishmeal, 15% fish oil) for 92 days. In particular, the study focused on the effect of these phytogenic compounds on the gut condition by analyzing the transcriptomic profiling (microarray analysis) and histological structure of the intestinal mucosa, as well as the histochemical properties of mucins stored in goblet cells. A total number of 506 differentially expressed genes (285 up- and 221 down-regulated) were found when comparing the transcriptomic profiling of the intestine from fish fed the control and MPLE diets. The gut transcripteractome revealed an expression profile that favored biological mechanisms associated to the 1) immune system, particularly involving T cell activation and differentiation, 2) gut integrity (i.e., adherens and tight junctions) and cellular proliferation, and 3) cellular proteolytic pathways. The histological analysis showed that the MPLE dietary supplementation promoted an increase in the number of intestinal goblet cells and modified the composition of mucins' glycoproteins stored in goblet cells, with an increase in the staining intensity of neutral mucins, as well as in mucins rich in carboxylated and weakly sulfated glycoconjugates, particularly those rich in sialic acid residues. The integration of transcriptomic and histological results showed that the evaluated MPLE from sage and lemon verbena is responsible for the maintenance of intestinal health, supporting gut homeostasis and increasing the integrity of the intestinal epithelium, which suggests that this phytogenic may be considered as a promising sustainable functional additive for aquafeeds.

Brij-functionalized chitosan nanocarrier system enhances the intestinal permeability of P-glycoprotein substrate-like drugs.

The highly expressed P-glycoprotein (Pgp) in the intestine plays a key role in preventing drugs across the intestinal epithelium, which linked by tight junctions (TJs). Thus increasing the oral bioavailability of Pgp substrate-like drugs (PSLDs) remains a great challenge. Herein, we construct a nanocarrier system derived from Brij-grafted-chitosan (BC) to enhance the oral bioavailability and therapeutic effect of berberine (BBR, a typical PLSD) against diabetic kidney disease. The developed BC nanoparticles (BC-NPs) are demonstrated to improve the intestinal permeability of BBR via transiently and reversibly modulating the intercellular TJs (paracellular pathway) and Pgp-mediated drug efflux (transcellular pathway). As compared to free BBR and chitosan nanoparticles, the BC-NPs enhanced the relative oral bioavailability of BBR in rats (4.4- and 2.7-fold, respectively), and the therapeutic potency of BBR in renal function and histopathology. In summary, such strategy may provide an effective nanocarrier system for oral delivery of BBR and PSLDs.

Nuciferine improves high-fat diet-induced obesity via reducing intestinal permeability by increasing autophagy and remodeling the gut microbiota.

Nuciferine (NF) has received extensive attention due to its medicinal value in the treatment of metabolic diseases, such as obesity; however, to date, the effects of NF on obesity-related intestinal permeability, autophagy and the gut microbiota have not been investigated. Herein, C57BL/6J mice were fed either a chow or a high-fat diet (HFD) with or without NF for 8 weeks. The results showed that NF supplement reduced weight gain, fat accumulation and intestinal permeability in the HFD mice accompanied by improved autophagy. Subsequently, an in vitro experiment was performed using Caco-2 and HT-29 cells, which showed that NF supplement not only promoted the formation of autophagosomes and autophagolysosomes, but also alleviated LPS-increased intestinal permeability. Importantly, NF supplement protected from LPS-induced paracellular permeability impairment after the administration of autophagy-related gene (Atg) 5 small-interfering RNA (siRNA). These results demonstrate that NF exerts beneficial effects on the intestinal permeability by improving autophagy. Furthermore, we also found that NF supplement lowered the abundance of Butyricimonas and increased the abundance of Akkermansia, an anti-obesity bacterium. Thus, overall, we demonstrated that NF supplement confers reduced intestinal permeability by improving autophagy and alters the composition of the gut microbiota in HFD-fed mice, thereby producing an anti-obesity effect.

Distinct Epigenetic Reprogramming, Mitochondrial Patterns, Cellular Morphology, and Cytotoxicity after Bee Venom Treatment.

BACKGROUND: Bee venom is a promising agent for cancer treatment due to its selective cytotoxic potential for cancer cells through apoptotic pathways. However, there is no evidence for changes in the epigenome and mitochondrial DNA copy numbers after bee venom application. The purpose of this study was to determine the impact of bee venom on cytosine modifications and mitochondrial DNA copy number variation. METHODS: A broad range of methods was applied to elucidate the impact of bee venom on neoplastic cells. These included MTT assay for detection of cytotoxicity, immunostaining of cytosine modifications and mitochondria, assessment of cellular morphology by flow cytometry, and quantification of mitochondrial DNA copy numbers using QPCR. RESULTS: Bee venom-induced cell death was selective for cancer cells, where it triggered a response characterized by alteration of cytosine modification. In contrast, normal cells were more resistant to DNA modifications. Furthermore, application of the venom resulted in variation of mitochondrial membrane permeability and mitochondrial DNA copy numbers, together with alterations in cell morphology, manifesting as reduced affected cell size. CONCLUSION: The study findings suggest that bee venom can be used as a selective DNA (de)methylating agent in cancer. Various agents (such as decitabine and 5-azacytidine) have been synthesized and developed for cancer treatment, and a range of syntheses and preparation and application methods have been described for these patented drugs. However, to the best of our knowledge, no previous research has investigated the use of bee venom or any component thereof for epigenetic therapy in cancer cells.

Effects of Anthocyanin on Intestinal Health: A Systematic Review.

Intestinal health relies on the association between the mucosal immune system, intestinal barrier and gut microbiota. Bioactive components that affect the gut microbiota composition, epithelial physical barrier and intestinal morphology were previously studied. The current systematic review evaluated evidence of anthocyanin effects and the ability to improve gut microbiota composition, their metabolites and parameters of the physical barrier; this was conducted in order to answer the question: "Does food source or extract of anthocyanin promote changes on intestinal parameters?". The data analysis was conducted following the PRISMA guidelines with the search performed at PubMed, Cochrane and Scopus databases for experimental studies, and the risk of bias was assessed by the SYRCLE tool. Twenty-seven studies performed in animal models were included, and evaluated for limitations in heterogeneity, methodologies, absence of information regarding allocation process and investigators' blinding. The data were analyzed, and the anthocyanin supplementation demonstrated positive effects on intestinal health. The main results identified were an increase of Bacteroidetes and a decrease of Firmicutes, an increase of short chain fatty acids production, a decrease of intestinal pH and intestinal permeability, an increase of the number of goblet cells and tight junction proteins and villi improvement in length or height. Thus, the anthocyanin supplementation has a potential effect to improve the intestinal health. PROSPERO (CRD42020204835).

Differential protection by anthocyanin-rich bilberry extract and resveratrol against lipid micelle-induced oxidative stress and monolayer permeability in Caco-2 intestinal epithelial cells.

Excess dietary fat, and associated bile acids, can impair intestinal barrier integrity, produce intestinal or systemic inflammation and promote tumorigenesis. Dietary polyphenols in foods such as berries display antioxidant and other protective effects in many biological systems, but little is known about their protective effects on intestinal epithelial cells exposed to dietary fat. In a Caco-2 cell model of dietary fat-induced intestinal epithelial cell cytotoxicity, oxidative stress and barrier impairment, we investigated the relative protection afforded by an anthocyanin-rich bilberry extract (ARBE) or resveratrol. Exposure of the cells to mixed micelles (MM) of fatty acids and bile acids for 24 h markedly increased intracellular reactive oxygen species (ROS) and mitochondrial superoxide generation, decreased cell viability, increased expression of TNF-α mRNA and disrupted differentiated monolayer integrity. Starting prior to exposure to MM, treatments with ARBE or resveratrol, at polyphenol concentrations from 1.25-20 µM, strongly attenuated MM-induced intracellular ROS generation, and ARBE but not resveratrol decreased mitochondrial superoxide generation. Both ARBE and resveratrol inhibited the MM-induced expression of TNF-α mRNA. In assessments of differentiated monolayer integrity by transepithelial electrical resistance (TEER) and paracellular permeability, resveratrol protection was apparent at 3 h of MM exposure, but less at 6 h and absent by 9 h. In contrast, ARBE largely reversed MM-induced impairment by 9 h, with TEER values reaching 82% of control and the MM-induced paracellular permeability reduced by 78%. While they appeared to act differently, the results suggest that dietary sources of anthocyanins and resveratrol can help confer resistance of intestinal epithelial cells to oxidative stress and inflammation, and resultant barrier dysfunction and tumorigenesis, induced by high dietary fat common in the Western diet.

Antiadhesive activity of hydroethanolic extract from bean pods of Phaseolus vulgaris (common bean) against uropathogenic E. coli and permeability of its constituents through Caco-2 cells monolayer.

ETHNOPHARMACOLOGICAL RELEVANCE: Phaseaoli pericarpium (bean pods) is a pharmacopeial plant material traditionally used as a diuretic and antidiabetic agents. Diuretic activity of pod extracts was reported first in 1608. Since then Phaseoli pericarpium tea figures in many textbooks as medicinal plant material used by patients. AIM OF THE STUDY: Despite the traditional use of extracts from Phaseolium vulgaris pericarp, limited information is available on bioactivity, chemical composition, and bioavailability of such preparations. The following study aimed to investigate the phytochemical composition, the in vitro permeability of selected extract's constituents over the Caco-2 permeation system, and potential antivirulence activity against uropathogenic Escherichia coli of a hydroalcoholic Phaseoli pericarpium extract (PPX) in vitro to support its traditional use as a remedy used in urinary tract infections. MATERIAL AND METHODS: The chemical composition of the extract PPX [ethanol:water 7:3 (v/v)] investigated by using UHPLC-DAD-MSn and subsequent dereplication. The permeability of compounds present in PPX was evaluated using the Caco-2 monolayer permeation system. The influence of PPX on uropathogenic E. coli (UPEC) strain NU14 proliferation and against the bacterial adhesion to T24 epithelial cells was determined by turbidimetric assay and flow cytometry, respectively. The influence of the extract on the mitochondrial activity of T24 host cells was monitored by MTT assay. RESULTS: LC-MSn investigation and dereplication, indicated PPX extract to be dominated by a variety of flavonoids, with rutin as a major compound, and soyasaponin derivatives. Rutin, selected soyasaponins and fatty acids were shown to permeate the Caco-2 monolayer system, indicating potential bioavailability following oral intake. The extract did not influence the viability of T24 cells after 1.5h incubation at 2 mg/mL and UPEC. PPX significantly reduced the bacterial adhesion of UPEC to human bladder cells in a concentration-dependent manner (0.5-2 mg/mL). Detailed investigations by different incubation protocols indicated that PPX seems to interact with T24 cells, which subsequently leads to reduced recognition and adhesion of UPEC to the host cell membrane. CONCLUSIONS: PPX is characterised by the presence of flavonoids (e.g. rutin) and saponins, from which selected compounds might be bioavailable after oral application, as indicated by the Caco-2 permeation experiments. Rutin and some saponins can be considered as potentially bioavailable after the oral intake. The concentration-dependent inhibition of bacterial adhesion of UPEC to T24 cells justifies the traditional use of Phaseoli pericarpium in the prevention and treatment of urinary tract infections.

Development, optimization and characterization of nanoemulsion loaded with clove oil-naftifine antifungal for the management of tinea.

Tinea is a common superficial infection caused by keratinophylic fungi called dermatophytes. The objective of the current investigation was to develop and optimize a self-nanoemulsion drug delivery system (SENDDs) using clove oil loaded with naftifine (NF). Clove oil possesses good anti-inflammatory and antifungal properties that can support naftifine action. Box-Behnken designs were used to prepare plain and naftifine loaded SENDDs. The plain SENDDs were evaluated for their globule size. The medicated formulations (NF-CO-SENDDs) were characterized by measuring their globular size, ex vivo % NF permeated, level of interleukin-31 in rats, and antifungal activity. The optimum clove oil level was found to be 10-17%, while NF-CO-SENDDs formulations displayed globular sizes ranging from 119 to 310 nm. The statistical design confirmed the synergistic effect of clove oil and NF in the treatment of fungal infections, confirming that the anti-inflammatory effect of clove oil can counteract the side effects of NF. The optimized formulation composed of 14% clove oil, 12.5 mg Naftifine, and prepared with an Smix ratio equaling 3:1, exhibited good antifungal and anti-inflammatory activity, achieving up to 2-, 3-, 5.75-, and 2.74-fold increases in the amount of permeated NF, steady-state flux, permeability, and diffusion coefficients, respectively, compared with a commercial product. Moreover, the optimum formulation revealed an adequate zeta potential value of 28.31 ± 1.37 mV and showed reasonable stability with no or mild signs of skin sensitivity. Therefore, the designed nanoemulsions containing a combination of clove oil and naftifine could be considered promising delivery systems for the treatment of tinea.

Tanshinone IIA attenuates AOM/DSS-induced colorectal tumorigenesis in mice via inhibition of intestinal inflammation.

CONTEXT: Tanshinone IIA is a natural extract derived from a Chinese medicinal herb with multiple bioactivities; however, whether and how tanshinone IIA protects against colorectal cancer (CRC) are uncertain. OBJECTIVE: We investigated the potential beneficial effects of tanshinone IIA in a colitis-associated colorectal tumorigenesis mouse model and its underlying mechanisms. MATERIALS AND METHODS: Male C57BL/6 mice were treated with azoxymethane (AOM) 10 mg/kg body weight and dextran sulphate sodium (2.5% DSS) to induce a colitis-associated cancer model. Tanshinone IIA (200 mg/kg body weight) was given to the mice intraperitoneally. After 12 weeks, all mice were sacrificed to measure tumour formation, intestinal permeability, neutrophil infiltration, and colonic inflammation. In addition, whether tanshinone IIA has inhibitory effects on neutrophil activation was determined through in vitro investigations. RESULTS: We observed that tanshinone IIA significantly decreased tumour formation in AOM/DSS-treated mice compared to AOM/DSS-treated alone mice (0.266 ± 0.057 vs. 0.78 ± 0.153, p = 0.013). Tanshinone IIA also decreased intestinal permeability compared to that in AOM/DSS-treated alone mice (3.12 ± 0.369 vs. 5.06 ± 0.597, p = 0.034) and consequently reduced neutrophil infiltration of the colonic mucosa (53.25 ± 8.85 vs. 107.6 ± 13.09, p = 0.014) as well as intestinal inflammation in mice. Mechanistically, tanshinone IIA downregulated the NF-κB signalling pathway in the colonic tumours of AOM/DSS-treated mice. In vitro assays further validated that tanshinone IIA suppressed LPS-induced neutrophil activation. CONCLUSION: These data suggest that tanshinone IIA alleviates colorectal tumorigenesis through inhibition of intestinal inflammation. Tanshinone IIA may have a therapeutic potential for CRC in clinical practice.

Human Intestinal Barrier: Effects of Stressors, Diet, Prebiotics, and Probiotics.

The objectives of this article are to understand the effects of stressors (nonsteroidal antiinflammatory drug, exercise, and pregnancy) and components in the diet, specifically prebiotics and probiotics, on intestinal barrier function. Stressors generally reduce barrier function, and these effects can be reversed by supplements such as zinc or glutamine that are among the substances that enhance the barrier. Other dietary factors in the diet that improve the barrier are vitamins A and D, tryptophan, cysteine, and fiber; by contrast, ethanol, fructose, and dietary emulsifiers increase permeability. Effects of prebiotics on barrier function are modest; on the other hand, probiotics exert direct and indirect antagonism of pathogens, and there are documented effects of diverse probiotic species, especially combination agents, on barrier function in vitro, in vivo in animal studies, and in human randomized controlled trials conducted in response to stress or disease. Clinical observations of benefits with combination probiotics in inflammatory diseases have simultaneously not appraised effects on intestinal permeability. In summary, probiotics and synbiotics enhance intestinal barrier function in response to stressor or disease states. Future studies should address the changes in barrier function and microbiota concomitant with assessment of clinical outcomes.