Relationships between the inhibitory efficacy and physicochemical properties of six organic acids and monolaurin against Bacillus weihenstephanensis KBAB4 growth in liquid medium.

Organic acids are widely used in foodstuffs to inhibit pathogen and spoiler growth. In this study, six organic acids (acetic, lactic, propionic, phenyllactic, caprylic, and lauric acid) and monolaurin were selected based on their physicochemical properties: their molecular structure (carbon chain length), their lipophilicity (logP), and their ability to dissociate in a liquid environment (pKa). The relation between these physicochemical properties and the inhibitory efficacy against B. weihenstephanensis KBAB4 growth was evaluated. After assessing the active form of these compounds against the strain (undissociated, dissociated or both forms), their MIC values were estimated in nutrient broth at pH 6.0 and 5.5 using two models (Lambert & Pearson, 2000; Luong, 1985). The use of two models highlighted the mode of action of an antibacterial compound in its environment, thanks to the additional estimation of the curve shape α or the Non-Inhibitory Concentration (NIC). The undissociated form of the tested acids is responsible for growth inhibition, except for lauric acid and monolaurin. Moreover, long-carbon chain acids have lower estimated MICs, compared to short-chain acids. Thus, the inhibitory efficacy of organic acids is strongly related to their carbon chain length and lipophilicity. Lipophilicity is the main mechanism of action of a membrane-active compound, it can be favored by long chain structure or high pKa in an acid environment like food.

Isolation and Structure Determination of cis-OPDA-α-Monoglyceride from Arabidopsis thaliana.

cis-12-oxo-Phytodieneoic acid-α-monoglyceride (1) was isolated from Arabidopsis thaliana. The chemical structure of 1 was elucidated based on exhaustive 1D and 2D NMR spectroscopic measurements and supported by FDMS and HRFDMS data. The absolute configuration of the cis-OPDA moiety in 1 was determined by comparison of 1H NMR spectra and ECD measurements. With respect to the absolute configuration of the ß-position of the glycerol backbone, the 2:3 ratio of (S) to (R) was determined by making ester-bonded derivatives with (R)-(+)-α-methoxy-α-trifluoromethylphenylacetyl chloride and comparing 1H NMR spectra. Wounding stress did not increase endogenous levels of 1, and it was revealed 1 had an inhibitory effect of A. thaliana post germination growth. Notably, the endogenous amount of 1 was higher than the amounts of (+)-7-iso-jasmonic acid and (+)-cis-OPDA in intact plants. 1 also showed antimicrobial activity against Gram-positive bacteria, but jasmonic acid did not. It was also found that α-linolenic acid-α-monoglyceride was converted into 1 in the A. thaliana plant, which implied α-linolenic acid-α-monoglyceride was a biosynthetic intermediate of 1.

Effects of dietary supplementation of glycerol monolaurate on laying performance, egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens.

The objective of this study was to evaluate the effects of different levels of glycerol monolaurate (GML) on laying performance, egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens. A total of 480 Hy-Line Variety Brown hens (age 54 wk) were randomly assigned to 5 treatments: the control group (basal diet) and 4 GML groups (basal diet supplemented with 100, 200, 300, and 400 mg/kg GML). Each treatment consisted of 8 replicates with 12 hens each and the trial lasted for 8 wk. The results showed that dietary inclusion of GML increased the ADFI in the entire experimental period and the average egg weight in wk 5 to 8 and wk 1 to 8 of the experiment (linear, P < 0.05). Dietary GML addition linearly increased albumen height, Haugh unit and yolk color, and quadratically increased eggshell thickness (P < 0.05). The serum SOD activity, T-AOC and IgG concentrations in the 200 mg/kg GML group, and GSH-Px activity in 200 and 300 mg/kg GML groups were increased, while the MDA concentration in 200 and 300 mg/kg GML groups was decreased than those in the control group (P < 0.05). The jejunal villus height and villus height: crypt depth in 300 mg/kg GML group were higher than that in the control group (P < 0.05). The mRNA expression of TLR4, IL-1ß and TNF-α in spleen and jejunum decreased with the increase of dietary GML concentration (linear, P < 0.05). In conclusion, dietary GML supplementation could improve egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens, and dietary 300 mg/kg GML inclusion is suggested.

Membrane-Disruptive Effects of Fatty Acid and Monoglyceride Mitigants on E. coli Bacteria-Derived Tethered Lipid Bilayers.

We report electrochemical impedance spectroscopy measurements to characterize the membrane-disruptive properties of medium-chain fatty acid and monoglyceride mitigants interacting with tethered bilayer lipid membrane (tBLM) platforms composed of E. coli bacterial lipid extracts. The tested mitigants included capric acid (CA) and monocaprin (MC) with 10-carbon long hydrocarbon chains, and lauric acid (LA) and glycerol monolaurate (GML) with 12-carbon long hydrocarbon chains. All four mitigants disrupted E. coli tBLM platforms above their respective critical micelle concentration (CMC) values; however, there were marked differences in the extent of membrane disruption. In general, CA and MC caused larger changes in ionic permeability and structural damage, whereas the membrane-disruptive effects of LA and GML were appreciably smaller. Importantly, the distinct magnitudes of permeability changes agreed well with the known antibacterial activity levels of the different mitigants against E. coli, whereby CA and MC are inhibitory and LA and GML are non-inhibitory. Mechanistic insights obtained from the EIS data help to rationalize why CA and MC are more effective than LA and GML at disrupting E. coli membranes, and these measurement capabilities support the potential of utilizing bacterial lipid-derived tethered lipid bilayers for predictive assessment of antibacterial drug candidates and mitigants.

Research Note: Comparative effects of liquid and dry applications of a combination of lysolecithin, synthetic emulsifier, and monoglycerides on growth performance, nutrient digestibility, and litter moisture in broilers fed diets of differing energy density.

Supplementation of a combination of lysolecithin, a synthetic emulsifier, and monoglycerides (LEX) in liquid and dry form to broiler diets with different energy levels was investigated to determine their effect on performance, litter quality and subsequent occurrence of footpad lesions. One thousand two hundred and forty-eight-day-old Ross 308 broilers were assigned to 1 of 6 treatments for a 42-day study: a basal diet with a normal energy content (NE); NE + 300 g/t LEX in liquid form (LEL); NE + 500 g/t LEX in dry form (LED); a basal diet with low energy (LE, -90 kcal/kg starter, -100 kcal/kg grower, finisher), LE + 300 g/t LEL and a LE + 500 g/t LED. Each treatment consisted of 13 pens of 16 birds each. Diets were fed in 3 phases (starter d 0-10, grower d 11-21, finisher d 22-42). Feed intake and weight were measured on d 0, 10, 21, and 42. On d 42 a litter sample was collected from each pen and 2 birds per pen were assessed for footpad lesions and breast scald. Data were analyzed using JMP 16, with means separation achieved using Tukey's HSD; significance was assumed at P < 0.05. Results showed a higher (P < 0.05) cumulative bodyweight gain with LEX supplementation (NE CON = 2,718 g, NE+LED = 2,829, NE+LEL = 2,895, LE CON = 2,722, LE+LED = 2,787, LE+LEL = 2,893; P = 0.0027). An increased feed intake was observed for the LE diets, however cumulative FCR of LE+LED and LE+LEL remained equal to the NE control (1.657 NE CON, 1.657 LE+LED, 1.623 LE+LEL; P > 0.05), suggesting LEX enabled the birds to compensate for the energy gap. Litter dry matter was significantly improved with both LED and LEL supplementation compared to the control groups, and resulted in lower (P < 0.05) occurrence and severity of footpad lesions and breast scalds. Considering the income over feed cost (IOFC) of the NE treatment as the reference point for comparison, all other treatments improved profitability, with NE+LEL and LE+LEL achieving the greatest IOFC with 154.58 and 175.96 €/1,000 birds respectively. In conclusion, feeding broilers a combination of lysophospholipids, a synthetic emulsifier and monoglycerides resulted in improved bird performance. The use of the LEX also improved litter quality and footpad health, therefore improving animal welfare indicators such as breast scald and footpad measurements.

Maternal supplementation with glycerol monolaurate improves the intestinal health of suckling piglets by inhibiting the NF-κB/MAPK pathways and improving oxidative stability.

Glycerol monolaurate (GML) is a food safe emulsifier and a kind of MCFA monoglyceride that has been proven to confer positive benefits in improving animal health, production and feed digestibility as a feed additive. This study aims to evaluate whether supplementation of a sow diet with GML could affect the intestinal barrier function and antioxidant status of newborn piglets and to explore its regulatory mechanism. A total of 80 multiparous sows were divided into two groups, which were fed a basal diet or a basal diet supplemented with 0.1% GML. The results indicated that maternal supplementation with GML significantly increased fat, lactose and protein in sow colostrum, as well as fat and protein in sow 14-day milk (P < 0.05). The results showed that GML significantly reduced the concentrations of IL-12 in the duodenum, TNF-α, IL-1ß and IL-12 in the jejunum, and IL-1ß in the ileum of piglets (P < 0.05). Higher concentrations of T-AOC, T-SOD, GSH and GSH-Px and lower MDA in the intestine were observed in the GML group than in the control group. Correspondingly, the villi height, crypt depth and the ratio of villi height to crypt depth (V/C) in the jejunum and the V/C in the ileum in the GML group were significantly higher than those in the control group (P < 0.05). Moreover, the GML group displayed significantly increased protein abundance of zonula occludens (ZO)-1, occludin, and claudin-1 in the small intestine (P < 0.05), mRNA expression of mucins (MUCs) in the small intestine (MUC-1, MUC-3 and MUC-4), and mRNA expression of porcine beta defensins (pBDs) in the duodenum (pBD1 and pBD2), jejunum (pBD1, pBD2 and pBD129) (P < 0.05), and ileum (pBD2, pBD3 and pBD114) (P < 0.05). Further research showed that GML significantly reduced the phosphorylation of the NF-κB/MAPK pathways in the small intestine (P < 0.05). In addition, the results of 16S rDNA sequencing showed that maternal supplementation with GML altered the colonic microbiotic structure of piglets, and reduced the relative abundance of Escherichia shigella. In summary, a sow diet supplemented with GML enhanced the offspring's intestinal oxidative stability and barrier function and attenuated the offspring's intestinal inflammatory response, possibly by suppressing the activation of the NF-κB/MAPK pathways.

Performance and gut health status of broilers fed diets supplemented with two graded levels of a monoglyceride blend.

The present study was undertaken to evaluate the efficacy of 2 graded levels (0.03 and 0.05% of diet) of a monoglyceride blend containing butyric, caprylic, and capric acids in broilers' diet for optimizing gut structure and animal growth performance. For this purpose, a total of 210, one-day-old male Ross 308 broiler chicks were randomly allocated to 3 experimental treatments using 7 replicates each and 10 birds/replicate. The treatment groups involved supplementation of blend of short and medium chain fatty acids at the level of 0, 0.03, and 0.05% of the diet for 42 d. The incorporation of mixes of monoglycerides into broilers' diet linearly improved BWG between d 0 and 21 (P = 0.034). At the end of trial, however, no significant changes were observed in performance indexes (BWG, FI, FCR). Jejunal morphometric parameters (villus height, crypt depth, and their ratio) remained unaltered with the monoglyceride supplementation on d 21. The results further showed that monoglycerides supplementation increased the goblet cell counts along the jejunal villi (P = 0.034) and crypt regions (P = 0.022), as well as it effectively modulated the mRNA abundances of tight junction protein (ZO-1, P = 0.033) and nutrient transporters (SGLT, PePT1; P = 0.005, 0.023, respectively) in the jejunum. Moreover, the downregulation in mRNA abundance of TNFα (P = 0.030) was observed with the monoglyceride supplementation. The SCFAs analysis of cecal contents showed no notable differences with monoglyceride blend supplementation when compared to the unsupplemented group. Collectively, high goblet cell numbers in the jejunum along with downregulation of the mRNA abundances of pro-inflammatory cytokines, upregulation of tight junction proteins, and nutrient transporters showed favorable responses of low doses of monoglycerides blend in broiler feeding. Further studies should be conducted in different rearing conditions to examine the effectiveness of such low levels of a monoglyceride blend in the modulation of gut structure, its functionality and animal performance.

The potential use of acylglycerols on the thermal inactivation of lactic acid bacteria for the manufacture of long-life fermented products.

The effect of acylglycerols on the thermal inactivation of lactic acid bacteria used in the production of fermented products was studied. The starting point was the observation of an increase in thermal sensitivity in the presence of an emulsifier based on mono- and diacylglycerols in the culture medium. Analysis of the emulsifier showed that monoacylglycerols were the compounds responsible for this effect, with monopalmitin being the main contributor. Monostearin, on the other hand, showed significantly less potentiating effect. Interestingly, monoacylglycerols showed a greater bactericidal effect when used individually than when used in combination. On the other hand, the rate of thermal inactivation observed in reconstituted skim milk emulsions was lower than in peptone water emulsions, showing that the presence of proteins and colloidal particles increased the resistance of bacteria to heat treatment. With respect to pH values, a reduction in pH from 6.6 to 5.5 promoted an increase in the rate of thermal death. However, at pH = 5.5, the enhancing bactericidal effect was only detectable when the heat treatment was performed at low temperatures but not at high temperatures. This finding is of interest, since it will allow the design of moderate heat treatments, combining the use of temperature with the addition of acylglycerols, to prolong the shelf life of products fermented with lactic acid bacteria, and minimizing the destruction of desirable compounds that were obtained by the fermentation process.

The Antiviral Activity of Caprylic Monoglyceride against Porcine Reproductive and Respiratory Syndrome Virus In Vitro and In Vivo.

Porcine reproductive and respiratory syndrome (PRRS) is a disease with a major economic impact in the global pig industry, and this study aims to identify potential anti-PRRSV drugs. We examined the cytotoxicity of four medium-chain fatty acids (MCFAs) (caprylic, caprylic monoglyceride, decanoic monoglyceride, and monolaurin) and their inhibition rate against PRRSV. Then the MCFAs with the best anti-PRRSV effect in in vitro assays were selected for subsequent in vivo experiments. Potential anti-PRRSV drugs were evaluated by viral load assay, pathological assay, and cytokine level determination. The results showed that caprylic monoglyceride (CMG) was the least toxic to cells of the four MCFAs, while it had the highest PRRSV inhibition rate. Then the animals were divided into a low-CMG group, a medium-CMG group, and a high-CMG group to conduct the in vivo evaluation. The results indicated that piglets treated with higher concentrations of caprylic monoglyceride were associated with lower mortality and lower viral load after PRRSV infection (p < 0.05). The pulmonary pathology of the piglets also improved after CMG treatment. The levels of pro-inflammatory cytokines (IL-6, IL-8, IL-1ß, IFN-γ, TNF-α) were significantly downregulated, and the levels of anti-inflammatory cytokine (IL-10) were significantly upregulated in the CMG-treated piglets compared to the positive control group (p < 0.05). Taken together, the present study revealed for the first time that caprylic monoglyceride has strong antiviral activity against PRRSV in vitro and in vivo, suggesting that caprylic monoglyceride could potentially be used as a drug to treat PRRS infection.

Lipophilic Compounds and Antibacterial Activity of Opuntia ficus-indica Root Extracts from Algeria.

The chemical composition, investigated by gas chromatography-mass spectrometry, and antibacterial activity of lipophilic extractives of three varieties of Opuntia ficus-indica roots from Algeria are reported in this paper for the first time. The results obtained revealed a total of 55 compounds, including fatty acids, sterols, monoglycerides and long chain aliphatic alcohols that were identified and quantified. ß-Sitosterol was found as the major compound of the roots of the three varieties. Furthermore, considerable amounts of essential fatty acids (ω3, ω6, and ω9) such as oleic, linoleic, and linolenic acids were also identified. The green variety was the richest among the three studied varieties. The antibacterial activity, evaluated with disc diffusion method, revealed that lipophilic extracts were effective mainly against Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) (19~23 mm). Gram-negative strains mainly Pseudomonas aeruginosa gave an inhibition zone of 18 mm, which is considered high antibacterial activity. The minimal inhibitory concentrations of the tested bacteria revealed interesting values against the majority of bacteria tested: 75-100 µg mL-1 for Bacillus sp., 250-350 µg/mL for the two Staphylococcus strains, 550-600 µg mL-1 for E. coli, and 750-950 µg mL-1 obtained with Pseudomonas sp. This study allows us to conclude that the lipophilic fractions of cactus roots possess interesting phytochemicals such as steroids, some fatty acids and long chain alcohols that acted as antibiotic-like compounds countering pathogenic strains.

Dietary emulsifier glycerol monodecanoate affects the gut microbiota contributing to regulating lipid metabolism, insulin sensitivity and inflammation.

Glycerol monodecanoate (GMD) is a medium-chain monoacylglycerol that possesses emulsifying and antibacterial properties. The common emulsifiers carboxymethylcellulose and polysorbate-80 have been reported to cause intestinal microbiota dysbiosis and metabolic disturbances. Glycerol monolaurate (GML), another medium-chain monoacylglycerol, is often used as an emulsifier and could improve metabolism by regulating the gut microbiota. However, research on the effects of GMD on the metabolism and gut microbiota remains scarce. Mice were fed a normal chow diet with or without GMD (150, 800, and 1600 mg kg-1) for 22 weeks. Metabolism indicators and related genes, gut microbiota, and fecal SCFAs were analyzed. The results demonstrated that GMD significantly improved insulin sensitivity, reduced the serum LPS level, and decreased pro-inflammation cytokines including IL-1ß, tumor necrosis factor (TNF), and monocyte chemotactic protein 1 (MCP-1). Additionally, 150 and 1600 mg kg-1 GMD could significantly lower the blood glucose content. 1600 mg kg-1 GMD improved cholesterol metabolism and related gene expression compared to 150 and 800 mg kg-1 GMD. Moreover, 150 and 800 mg kg-1 GMD up-regulated the abundance of Lactobacillus and Turicibacter, while 1600 mg kg-1 GMD significantly up-regulated the abundance of Bifidobacterium. Our findings indicated that different doses of GMD had inconsistent effects on lipid metabolism by differentially altering the gut microbiota composition. Meanwhile, all doses of GMD showed excellent effects on increasing insulin sensitivity and improving inflammation.

Glycerol monolaurate inhibition of human B cell activation.

Glycerol monolaurate (GML) is a naturally occurring antimicrobial agent used commercially in numerous products and food items. GML is also used as a homeopathic agent and is being clinically tested to treat several human diseases. In addition to its anti-microbial function, GML suppresses immune cell proliferation and inhibits primary human T cell activation. GML suppresses T cell activation by altering membrane dynamics and disrupting the formation of protein clusters necessary for intracellular signaling. The ability of GML to disrupt cellular membranes suggests it may alter other cell types. To explore this possibility, we tested how GML affects human B cells. We found that GML inhibits BCR-induced cytokine production, phosphorylation of signaling proteins, and protein clustering, while also changing cellular membrane dynamics and dysregulating cytoskeleton rearrangement. Although similar, there are also differences between how B cells and T cells respond to GML. These differences suggest that unique intrinsic features of a cell may result in differential responses to GML treatment. Overall, this study expands our understanding of how GML impacts the adaptive immune response and contributes to a broader knowledge of immune modulating monoglycerides.

Reversible Monoacylglycerol Lipase Inhibitors: Discovery of a New Class of Benzylpiperidine Derivatives.

Monoacylglycerol lipase (MAGL) is the enzyme responsible for the metabolism of 2-arachidonoylglycerol in the brain and the hydrolysis of peripheral monoacylglycerols. Many studies demonstrated beneficial effects deriving from MAGL inhibition for neurodegenerative diseases, inflammatory pathologies, and cancer. MAGL expression is increased in invasive tumors, furnishing free fatty acids as pro-tumorigenic signals and for tumor cell growth. Here, a new class of benzylpiperidine-based MAGL inhibitors was synthesized, leading to the identification of 13, which showed potent reversible and selective MAGL inhibition. Associated with MAGL overexpression and the prognostic role in pancreatic cancer, derivative 13 showed antiproliferative activity and apoptosis induction, as well as the ability to reduce cell migration in primary pancreatic cancer cultures, and displayed a synergistic interaction with the chemotherapeutic drug gemcitabine. These results suggest that the class of benzylpiperidine-based MAGL inhibitors have potential as a new class of therapeutic agents and MAGL could play a role in pancreatic cancer.

Monoglyceride reduces viability of porcine epidemic diarrhoea virus in feed and prevents disease transmission to post-weaned piglets.

Outbreaks of African swine fever virus (ASFv) and porcine epidemic diarrhoea virus (PEDv) have revealed the susceptibility of livestock to disease transmitted through feed. Several viruses, including PEDv, survive in feed and may introduce disease that causes significant morbidity and mortality. In 2013, PEDv, which causes severe diarrhoea and vomiting, reached North America after spreading for decades across Eurasia. The global exchange of ingredients has created demand for products that prevent disease transmission from feed. Formaldehyde-based products are highly effective at inactivating enveloped viruses when applied at 3.25 kg/t. Alternative products to formaldehyde, including carboxylic acids, essential oils and medium chain fatty acids (MCFAs), have exhibited mixed efficacy against PEDv and require application rates higher than formaldehyde. Amphiphilic molecules like MCFAs disrupt the bilayer-lipid membranes that protect viral nucleic acids through the formation of micelles. Monoglycerides form micelles at lower concentrations than MCFAs, which suggests they may be more potent against enveloped viruses. The potential efficacy of monoglycerides against enveloped viruses in feed led to the development and examination of an experimental monoglyceride blend. The proprietary monoglyceride blend significantly (p < .0001) reduced PEDv viability in vitro after application to feed at 1.5, 2.5 and 3.5 kg/t. The monoglyceride was tested in a natural feeding behaviour challenge model in piglets. The feed was contaminated with ice-blocks containing viable PEDv, and the piglets were exposed to PEDv through the feed bin for 20 days. At the end of the 20-day challenge period, all pigs were rectally swabbed and tested for PEDv by qPCR. In the untreated control group 54.8% of the piglets tested positive for PEDv, whereas none of the MCFA-treated feed (10 kg/t inclusion) transmitted PEDv. Strikingly, the monoglyceride-treated groups (1.5, 2.5 and 3.5 kg/t) all exhibited 100% protection from PEDv. These data support the use of this proprietary monoglyceride blend in mitigation and prevention of viral disease transmission to piglets from contaminated feed.

In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus plantarum pH3A, monolaurin, and grapefruit seed extract.

Helicobacter pylori infection is the most common cause of gastritis and gastric ulcers. Considering the severe side effects of current antibiotic therapies, it is crucial to find an alternate treatment for H. pylori infection. In this study, we investigated the anti-H. pylori effects of a newly isolated strain of Lactobacillus plantarum (pH3A), monolaurin, grapefruit seed extract (GSE), and their synergies in vitro and in vivo. Monolaurin and GSE suppressed H. pylori growth and urease activity at a minimal inhibitory concentration (MIC) of 62.5 ppm. Live cells and cell-free culture supernatant (CFCS) of L. plantarum pH3A with or without pH adjustment also significantly inhibited H. pylori growth. Although synergy was not observed between monolaurin and GSE, the addition of CFCS significantly enhanced their anti-H. pylori activities. Moreover, L. plantarum pH3A significantly decreased the ability of H. pylori to adhere to AGS cells and interleukin (IL)-8 production in the H. pylori-stimulated AGS cell line. The addition of GSE or monolaurin strengthened these effects. In the in vivo study, H. pylori colonization of the mouse stomach and total serum IgG production were significantly reduced by L. plantarum pH3A treatment, but the addition of monolaurin or GSE did not contribute to these anti-H. pylori activities. Therefore, the L. plantarum pH3A strain can potentially be applied as an alternative anti-H. pylori therapy, but evidence of its synergy with monolaurin or GSE in vivo is still lacking.

Glycerol Monolaurate Ameliorated Intestinal Barrier and Immunity in Broilers by Regulating Intestinal Inflammation, Antioxidant Balance, and Intestinal Microbiota.

This study was conducted to investigate the impact of glycerol monolaurate (GML) on performance, immunity, intestinal barrier, and cecal microbiota in broiler chicks. A total of 360 one-day-old broilers (Arbor Acres) with an average weight of 45.7 g were randomly allocated to five dietary groups as follows: basal diet and basal diets complemented with 300, 600, 900, or 1200 mg/kg GML. Samples were collected at 7 and 14 days of age. Results revealed that feed intake increased (P < 0.05) after 900 and 1200 mg/kg GML were administered during the entire 14-day experiment period. Dietary GML decreased (P < 0.05) crypt depth and increased the villus height-to-crypt depth ratio of the jejunum. In the serum and jejunum, supplementation with more than 600 mg/kg GML reduced (P < 0.05) interleukin-1ß, tumor necrosis factor-α, and malondialdehyde levels and increased (P < 0.05) the levels of immunoglobulin G, jejunal mucin 2, total antioxidant capacity, and total superoxide dismutase. GML down-regulate (P < 0.05) jejunal interleukin-1ß and interferon-γ expression and increased (P < 0.05) the mRNA level of zonula occludens 1 and occludin. A reduced (P < 0.05) expression of toll-like receptor 4 and nuclear factor kappa-B was shown in GML-treated groups. In addition, GML modulated the composition of the cecal microbiota of the broilers, improved (P < 0.05) microbial diversity, and increased (P < 0.05) the abundance of butyrate-producing bacteria. Spearman's correlation analysis revealed that the genera Barnesiella, Coprobacter, Lachnospiraceae, Faecalibacterium, Bacteroides, Odoriacter, and Parabacteroides were related to inflammation and intestinal integrity. In conclusion, GML ameliorated intestinal morphology and barrier function in broiler chicks probably by regulating intestinal immune and antioxidant balance, as well as intestinal microbiota.

Docosahexaenoic acid monoglyceride induces apoptosis and autophagy in breast cancer cells via lipid peroxidation-mediated endoplasmic reticulum stress.

Epidemiologic and preclinical studieshave shown that marine n-3 polyunsaturated fatty acids (n-3 PUFAs) elicit promising chemoprevention against breast cancer. Docosahexaenoic acid monoglyceride (MAG-DHA), a docosahexaenoic acid sn-1-monoacylglycerol does not required pancreatic lipase to be absorbed, eliciting a better bioavailability when compared with other formulations such as DHA-free fatty acid, DHA-triglycerol, or DHA-ethyl ester. However, the anticancer actions and underlying mechanisms of MAG-DHA on breast cancer remain to be assessed. In this study, MAG-DHA induced significant growth inhibition in MCF-7 and MDA-MB-231 breast cancer cells in a dose-dependent manner. MAG-DHA treatment (80 µM) led to 83.8 and 94.3% growth inhibition between MCF-7 and MDA-MB-231 cells, respectively. MAG-DHA-induced growth inhibition was tightly associated with apoptosis, as evidenced by increased active forms of caspase-3, poly (ADP-ribose) polymerase (PARP) and caspase-12. In particular, MAG-DHA-induced apoptosis was triggered by oxidative stress-mediated endoplasmic reticulum (ER) stress, as evidenced by activation of the PERK-eIF2α pathway in ER. MAG-DHA treatment also strongly suppressed the growth of E0771 murine breast cancer xenografts, significant differences of tumor volume were found between MAG-DHA group (0.271 cm3 ) and control group (0.875 cm3 ) after 15 daily MAG-DHA treatments. The in vitro antibreast cancer mechanism of MAG-DHA was supported by the in vivo xenograft model. In addition, MAG-DHA-induced ER stress concomitantly triggered autophagy in these cancer cells, and the induction of autophagy suppressed its ability to induce apoptotic cell death. Our data suggested that MAG-DHA as dietary supplement, in combination with autophagy inhibitors may be a useful therapeutic strategy in treating breast cancer.

Effect of supplemental glycerol monolaurate and oregano essential oil blend on the growth performance, intestinal morphology, and amino acid digestibility of broiler chickens.

BACKGROUND: This experiment tested the impact of the combined supplementation of glycerol monolaurate (GLM) and oregano essential oil (EO) to broiler diets. Growth performance, metabolic response, immune status, apparent ileal digestibility coefficient (AID%), and intestinal histomorphology were assessed. Three-day-old Ross-308 broilers (76.62 g ± 0.50, n = 240) were randomly allocated into 4 experimental groups (6 replicates/group and 10 chicks/replicate). Birds were fed corn-soybean meal basal diets supplemented with four levels of GLM and oregano EO blend: 0, 0.15, 0.45, and 0.75% for 35 days. RESULTS: During the starter period, dietary GLM and oregano EO did not show significant (P > 0.05) changes in growth performance. During the grower period, GLM and oregano EO supplemented groups showed a linear and quadratic decline in FCR. During the finisher and overall performance, a linear increase in the body weight (BW), body weight gain (BWG), the protein efficiency ratio (PER), and relative growth rate (RGR), and a linear decrease in the FCR at 0.75% dietary level of GLM and oregano EO compared to the control. The broken-line regression model showed that the optimum dietary level of GLM and oregano EO blend was 0.58% based on final BW and FCR. The 0.45% or 0.15% dietary level of supplemented additives lowered (P < 0.05) the AID% of threonine and arginine, respectively, with no change in the AID% of other assessed amino acids at all dietary levels. Muscle thickness in jejunum and ileum in all dietary supplemented groups was increased (P < 0.05); however, such increase (P < 0.05) in the duodenum was shown at 0.45 and 0.75% dietary levels. All GLM and oregano EO supplemented groups showed increased (P < 0.05) duodenal, jejunal, and ileal villus height. The 0.15 and/or 0.75% dietary levels of supplemented additives increased (P < 0.05) the ileal and duodenal crypt depth, respectively, with a decreased (P < 0.05) duodenal crypt depth at 0.15% dietary level. The goblet cell count in ileum decreased (P < 0.05) in all GLM and oregano EO supplemented groups, but this decreased count (P < 0.05) was detected in jejunum at 0.45 and 0.75% dietary levels. The GLM and oregano EO supplemented groups did not show significant (P > 0.05) changes in the assessed metabolic and immune status parameters. Economically, the total return and performance index was increased at 0.75% dietary level. CONCLUSION: Better growth performance was achieved at a 0.75 % dietary level of GLM and oregano EO by improving most intestinal morphometric measures. The optimum dietary level detected was 0.58%. The lack of influence of supplemented additives on chickens' immune and metabolic responses could indicate a lack of synergy between GLM and oregano EO.

Antibacterial Filtration Membranes Based on PVDF-co-HFP Nanofibers with the Addition of Medium-Chain 1-Monoacylglycerols.

The efficiency of filtration membranes is substantially lowered by bacterial attachments and potential fouling processes, which reduce their durability and lifecycle. The antibacterial and antifouling properties exhibited by the added materials play a substantial role in their application. We tested a material poly(vinylidene fluoride)-co-hexafluoropropylene (PDVF-co-HFP) based on an electrospun copolymer, where an agent was incorporated with a small amount of ester of glycerol consecutively with caprylic, capric, and lauric acids. Each of these three materials differing in the esters (1-monoacylglycerol, 1-MAG) used was prepared with three weighted concentrations of 1-MAG (1, 2, and 3 wt %). The presence of 1-MAG with an amphiphilic structure resulted in the hydrophilic character of the prepared materials that contributed to the filtration performance. The tested materials (membranes) were characterized with rheological, optical (scanning electron microscopy, SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and other methods to evaluate antibacterial and antifouling activities. The pure water flux was 6 times higher than that of the neat PVDF-co-HFP membrane when the added 1-MAG attained only 1 wt %. It was experimentally shown that the PVDF-co-HFP/1-MAG membrane with high wettability improved antibacterial activity and antifouling ability. This membrane is highly promising for water treatment due to the safety of antibacterial 1-MAG additives.

Suppression of human T cell activation by derivatives of glycerol monolaurate.

Glycerol monolaurate (GML), a naturally occurring monoglyceride, is widely used commercially for its antimicrobial properties. Interestingly, several studies have shown that GML not only has antimicrobial properties but is also an anti-inflammatory agent. GML inhibits peripheral blood mononuclear cell proliferation and inhibits T cell receptor (TCR)-induced signaling events. In this study, we perform an extensive structure activity relationship analysis to investigate the structural components of GML necessary for its suppression of human T cell activation. Human T cells were treated with analogs of GML, differing in acyl chain length, head group, linkage of acyl chain, and number of laurate groups. Treated cells were then tested for changes in membrane dynamics, LAT clustering, calcium signaling, and cytokine production. We found that an acyl chain with 12-14 carbons, a polar head group, an ester linkage, and a single laurate group at any position are all necessary for GML to inhibit protein clustering, calcium signaling, and cytokine production. Removing the glycerol head group or replacing the ester linkage with a nitrogen prevented derivative-mediated inhibition of protein cluster formation and calcium signaling, while still inhibiting TCR-induced cytokine production. These findings expand our current understanding of the mechanisms of action of GML and the of GML needed to function as a novel immunosuppressant.