Pachymic acid (PA) inhibits ferroptosis of cardiomyocytes via activation of the AMPK in mice with ischemia/reperfusion-induced myocardial injury.

Pachymic acid (PA) is a lanostane-type triterpenoid with various pharmacological effects. However, little is known about the effect of PA on myocardial infarction (MI) induced by ischemia/reperfusion (I/R). In this study, we aimed to investigate the protective effect of PA and its underlying mechanism. A cellular MI model was established by oxygen-glucose deprivation and reperfusion (OGD/R) treatment in HL-1 cardiomyocytes, and we found that OGD/R treatment decreased cell viability and glutathione peroxide (GSH-Px) activity, increased Fe2+ concentration and lactate dehydrogenase (LDH) activity, promoted malondialdehyde (MDA) and reactive oxygen species (ROS) production, and inhibited the expression of ferroptosis marker proteins SLC7A11 and GPX4 in a time-dependent manner. OGD/R-induced HL-1 cells were pretreated with different concentrations of PA (0, 20, 40, 60 µg/mL) for 24 h, and toxicological experiments showed that 150 µg/mL PA decreased cell viability, while low concentrations of PA had no toxic effect on cells. 20 µg/mL PA reversed the inhibitory effect of OGD/R on cell viability, reduced MDA and ROS production, and Fe2+ accumulation, increased GSH-Px activity and the expression of SLC7A11 and GPX4, and decreased LDH activity, especially at 60 µg/mL PA. Meanwhile, PA promoted the phosphorylation of IRS-1, AKT, and AMPK proteins in a dose-dependent manner. AICAR, an AMPK activator, inhibited ferroptosis, while STO-609, an AMPK inhibitor, largely abolished the effect of PA on OGD/R-induced ferroptosis of HL-1 cells. In addition, PA inhibited ferroptosis and myocardial I/R injury in wild-type mice and AMPK knockout (AMPK-/- ) mice. Collectively, PA inhibited ferroptosis of cardiomyocytes through activating of the AMPK pathway, thereby alleviating myocardial I/R injury in mice.

Identification of Genipin as a Potential Treatment for Type 2 Diabetes.

The prevalence of type 2 diabetes (T2D) has been rising dramatically in many countries around the world. The main signatures of T2D are insulin resistance and dysfunction of ß-cells. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing the functional decline of pancreatic ß-cells in T2D patients. It has been well recognized that glucagon-like peptide-1 (GLP-1), which is an incretin hormone secreted from intestinal L-cells, plays a vital role in regulating glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting ß-cell function. We found that genipin, a natural compound from Elli, can directly target intestinal L-cells, leading to the secretion of GLP-1. Incubation of the cells with genipin elicited a rapid increase in intracellular Ca2+. Inhibition of PLC ablated genipin-stimulated Ca2+ increase and GLP-1 secretion, suggesting that genipin-induced GLP-1 release from cells is dependent on the PLC/Ca2+ pathway. In vivo, acute administration of genipin stimulated GLP-1 secretion in mice. Chronically, treatment with genipin via oral gavage at 50 mg/kg/day for 6 weeks reversed hyperglycemia and insulin resistance in high-fat-diet (HFD)-induced obese mice. Moreover, genipin alleviated the impaired lipid metabolism and decreased lipid accumulation in the liver of obese mice. These results suggest that naturally occurring genipin might potentially be a novel agent for the treatment of T2D and diet-induced fatty liver disease.

Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway.

Resveratrol, a natural compound in grapes and red wine, has drawn attention due to potential cardiovascular-related health benefits. However, its effect on vascular inflammation at physiologically achievable concentrations is largely unknown. In this study, resveratrol in concentrations as low as 1 µm suppressed TNF-α-induced monocyte adhesion to human EA.hy926 endothelial cells (ECs), a key event in the initiation and development of atherosclerosis. Low concentrations of resveratrol (0.25-2 µm) also significantly attenuated TNF-α-stimulated mRNA expressions of MCP-1/CCL2 and ICAM-1, which are vital mediators of EC-monocyte adhesion molecules and cytokines for cardiovascular plaque formation. Additionally, resveratrol diminished TNF-α-induced IκB-α degradation and subsequent nuclear translocation of NF-κB p65 in ECs. In the animal study, resveratrol supplementation in diet significantly diminished TNF-α-induced increases in circulating levels of adhesion molecules and cytokines, monocyte adhesion to mouse aortic ECs, F4/80-positive macrophages and VCAM-1 expression in mice aortas and restored the disruption in aortic elastin fiber caused by TNF-α treatment. The animal study also confirmed that resveratrol blocks the activation of NF-κB In Vivo. In conclusion, resveratrol at physiologically achievable concentrations displayed protective effects against TNF-α-induced vascular endothelial inflammation in vitro and In Vivo. The ability of resveratrol in reducing inflammation may be associated with its role as a down-regulator of the NF-κB pathway.

The Emerging Role of Polyphenols in the Management of Type 2 Diabetes.

Type 2 diabetes (T2D) is a fast-increasing health problem globally, and it results from insulin resistance and pancreatic ß-cell dysfunction. The gastrointestinal (GI) tract is recognized as one of the major regulatory organs of glucose homeostasis that involves multiple gut hormones and microbiota. Notably, the incretin hormone glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells plays a pivotal role in maintaining glucose homeostasis via eliciting pleiotropic effects, which are largely mediated via its receptor. Thus, targeting the GLP-1 signaling system is a highly attractive therapeutic strategy to treatment T2D. Polyphenols, the secondary metabolites from plants, have drawn considerable attention because of their numerous health benefits, including potential anti-diabetic effects. Although the major targets and locations for the polyphenolic compounds to exert the anti-diabetic action are still unclear, the first organ that is exposed to these compounds is the GI tract in which polyphenols could modulate enzymes and hormones. Indeed, emerging evidence has shown that polyphenols can stimulate GLP-1 secretion, indicating that these natural compounds might exert metabolic action at least partially mediated by GLP-1. This review provides an overview of nutritional regulation of GLP-1 secretion and summarizes recent studies on the roles of polyphenols in GLP-1 secretion and degradation as it relates to metabolic homeostasis. In addition, the effects of polyphenols on microbiota and microbial metabolites that could indirectly modulate GLP-1 secretion are also discussed.

Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice.

We recently reported that epicatechin, a bioactive compound that occurs naturally in various common foods, promoted general health and survival of obese diabetic mice. It remains to be determined whether epicatechin extends health span and delays the process of aging. In the present study, epicatechin or its analogue epigallocatechin gallate (EGCG) (0.25% w/v in drinking water) was administered to 20-mo-old male C57BL mice fed a standard chow. The goal was to determine the antiaging effect. The results showed that supplementation with epicatechin for 37 wk strikingly increased the survival rate from 39 to 69%, whereas EGCG had no significant effect. Consistently, epicatechin improved physical activity, delayed degeneration of skeletal muscle (quadriceps), and shifted the profiles of the serum metabolites and skeletal muscle general mRNA expressions in aging mice toward the profiles observed in young mice. In particular, we found that dietary epicatechin significantly reversed age-altered mRNA and protein expressions of extracellular matrix and peroxisome proliferator-activated receptor pathways in skeletal muscle, and reversed the age-induced declines of the nicotinate and nicotinamide pathway both in serum and skeletal muscle. The present study provides evidence that epicatechin supplementation can exert an antiaging effect, including an increase in survival, an attenuation of the aging-related deterioration of skeletal muscles, and a protection against the aging-related decline in nicotinate and nicotinamide metabolism.-Si, H., Wang, X., Zhang, L., Parnell, L. D., Admed, B., LeRoith, T., Ansah, T.-A., Zhang, L., Li, J., Ordovás, J. M., Si, H., Liu, D., Lai, C.-Q. Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice.

Large-scale manufacture of VP2 VLP vaccine against porcine parvovirus in Escherichia coli with high-density fermentation.

Porcine parvovirus (PPV) virus-like particles (VLPs) are a potential vaccine candidate for the prevention of parvovirus-induced reproductive failure in pregnant sows. Currently, the Escherichia coli (E. coli) expression system is the most cost-efficient to express recombinant proteins. To overcome the limitations of protein misfolding and to prepare soluble highly bioactive antigen and high yields of protein, we optimized the PPV-VP2 gene, subcloned it into pET24a, pET26b, pET28a, and pET30a, and transformed it into E. coli BL21(DE3)-Tf16 competent cells. The pET28a plasmid was selected for further manipulations because it expressed high levels of the bioactive PPV-VP2 protein. Under optimal high-density fermenting conditions in a 70-L fermenter, the total yield of wet weight E. coli cells was 124.86 g/L, and PPV-VP2 protein was 2.5 g/L. After large-scale purification with Triton X-114 two-phase extraction as well as activated carbon powder adsorption, hemagglutination (HA) titers in the purified PPV-VP2 protein reached 219 and endotoxin was reduced to 2500 EU/mL. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results indicated that the purified PPV-VP2 protein self-assembled into VLPs. Immunogenicity assays in guinea pigs and pigs indicated that the ISA-201 VG adjuvanted PPV-VP2 VLP vaccine elicited hemagglutination inhibition (HI) and virus neutralization (VN) antibody titers comparable with PPV commercial inactivated vaccines, whereas viral loads in the spleen and liver of challenged guinea pigs were significantly reduced. In conclusion, our study provides a method for producing the PPV-VLP vaccine against PPV infection in E. coli and may offer a novel strategy for the soluble expression of other vaccine antigens.

Antibiotics-induced perturbations in gut microbial diversity influence metabolic phenotypes in a murine model of high-fat diet-induced obesity.

Gut microbiota play a key role in the regulation of obesity and associated metabolic disorders. To study the relationship between them, antibiotics have been widely used to generate pseudo-germ-free rodents as control models. However, it is not clear whether antibiotics impact an animal's metabolic phenotype. Therefore, the effect of antibiotics-induced gut microbial perturbations on metabolic phenotypes in high-fat diet (HFD) fed mice was investigated. The results showed that antibiotics perturbed gut microbial composition and structure. Community diversity and richness were reduced, and the phyla Firmicutes/Bacteroidetes (F/B) ratio was decreased by antibiotics. Visualization of Unifrac distance data using principal component analysis (PCA) and unweighted pair-group method with arithmetic mean (UPGAM) demonstrated that fecal samples of HFD-fed mice separated from those of chow diet (CD) fed mice. Fecal samples from antibiotics-treated and non-treated mice were clustered into two different microbial populations. Moreover, antibiotics suppressed HFD-induced metabolic features, including body weight gain (BWG), liver weight (LW), epididymal fat weight (EFW), and serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), fasting blood glucose (FBG), and insulin (INS) significantly (P < 0.05). Lachnospiraceae, Ruminiclostridium and Helicobacter, biomarkers of mouse gut microbiota before treatment by antibiotics, were positively correlated with obesity phenotypes significantly (P < 0.05) and were decreased by (92.95 ± 5.09) %, (97.73 ± 2.09) % and (99.48 ± 0.21) % respectively after 30 days of treatment by antibiotics. However, Bacteroidia were enriched in HFD-fed antibiotics-treated mice and were negatively correlated with obesity phenotypes significantly (P < 0.05). We suggested that the antibiotics-induced depletion of Lachnospiraceae, Ruminiclostridium, and Helicobacter, and the decrease in F/B ratio in gut microbiota played a role in the prevention of HFD-induced obesity in mice.

Synergetic Sensing Effect of Sodium Carboxymethyl Cellulose and Bismuth on Cadmium Detection by Differential Pulse Anodic Stripping Voltammetry.

In the present work, a novel electrochemical sensor was developed for the detection of trace cadmium with high sensitivity and selectivity in an easy and eco-friendly way. Firstly, a glassy carbon electrode (GCE) was modified with nontoxic sodium carboxymethyl cellulose (CMC) by a simple drop-casting method, which was applied to detect cadmium by differential pulse anodic stripping voltammetry (DPASV) in a solution containing both target cadmium and eco-friendly bismuth ions, based on a quick electro-codeposition of these two metal ions on the surface of the modified electrode (CMC-GCE). Investigated by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and Fourier transform infrared spectroscopy (FT-IR), both CMC (with good film-forming ability) and bismuth (with well-defined stripping signal) were found to be well complexed with target cadmium, leading to vital signal amplification for cadmium detection at a sub-nanomolar level. Under the optimal conditions, the proposed sensor exhibited a good linear stripping signal response to cadmium (Ⅱ) ion, in a concentration range of 0.001 µmol/L-1 µmol/L with a limit of detection of 0.75 nmol/L (S/N = 3). Meanwhile, the results demonstrate that this novel electrochemical sensor has excellent sensitivity and reproducibility, which can be used as a promising detection technique for testing natural samples such as tap water.

Trigger factor assisted self-assembly of canine parvovirus VP2 protein into virus-like particles in Escherichia coli with high immunogenicity.

Canine parvovirus (CPV) has been considered to be an important pathogen, which can cause acute infectious disease in canids. Although current vaccines are effective in preventing CPV infection, safety problems still remain unsolved. In this study, a subunit vaccine against CPV based on virus-like particles (VLPs) with good safety and immunogenicity is reported. Soluble CPV VP2 protein was produced by co-expression of chaperone trigger factor (Tf16) in Escherichia coli (E.coli), and assembled into CPV VLPs which could be affected by NaCl and pH. At 250 mM NaCl pH 8.0, the VLPs co-expressed with Tf16 had similar size (25 nm) and shape with the authentic virus capsid under the transmission electron microscopy (TEM), which is also in accordance with the dynamic light scattering (DLS) data. Immunization with these particles could induce high-titer hemagglutination inhibition (1:12288) and neutralizing antibodies (1:6144) in guinea pigs. Splenic cells of them could secrete IFN-γ and IL-4 after stimulation by CPV. Thus, the VLPs produced by the new approach with high yield and immunogenicity could be a potential candidate for CPV vaccine.

Genetic and immunogenicity analysis of porcine circovirus type 2 strains isolated in central China.

Porcine circovirus type 2 (PCV2) is an economically important pathogen in domestic pigs and wild boars all around the world. To understand the molecular epidemiology of PCV2 strains circulating in central China and to provide a potential vaccine candidate strain, we analyzed the genetic variations of 46 PCV2 isolates circulating from 2009 to 2016 in Henan Province (24 detected in the field from 2009-2013 and 22 from 2013-2016) and evaluated the efficacy of an isolate as a vaccine candidate strain in a mouse model. We found that PCV2b was the predominant genotype and PCV2b-1C was the main subtype. The PCV2 isolate DF-1, which had a virus titer of 106.5 TCID50/mL and a stable genome, was selected and used to immunize Kunming mice. Enzyme-linked immunosorbent assay (ELISA), immunoperoxidase monolayer assay (IPMA), and virus neutralization test (VNT) results indicated that the DF-1 vaccine candidate strain could elicit a level of specific antibodies and neutralizing antibodies similar to those induced by a commercial vaccine. Polymerase chain reaction (PCR) detection of virus in vaccinated mice after challenge revealed that DF-1 vaccination was effective in clearing the virus in different tissues. Hence, the PCV2 isolate DF-1, a circulating subtype of PCV2b-1C, might be used as a potential vaccine candidate strain.

The Flavonoid Kaempferol Ameliorates Streptozotocin-Induced Diabetes by Suppressing Hepatic Glucose Production.

In diabetes mellitus, the excessive rate of glucose production from the liver is considered a primary contributor for the development of hyperglycemia, in particular, fasting hyperglycemia. In this study, we investigated whether kaempferol, a flavonol present in several medicinal herbs and foods, can be used to ameliorate diabetes in an animal model of insulin deficiency and further explored the mechanism underlying the anti-diabetic effect of this flavonol. We demonstrate that oral administration of kaempferol (50 mg/kg/day) to streptozotocin-induced diabetic mice significantly improved hyperglycemia and reduced the incidence of overt diabetes from 100% to 77.8%. This outcome was accompanied by a reduction in hepatic glucose production and an increase in glucose oxidation in the muscle of the diabetic mice, whereas body weight, calorie intake, body composition, and plasma insulin and glucagon levels were not altered. Consistently, treatment with kaempferol restored hexokinase activity in the liver and skeletal muscle of diabetic mice while suppressed hepatic pyruvate carboxylase activity and gluconeogenesis. These results suggest that kaempferol may exert antidiabetic action via promoting glucose metabolism in skeletal muscle and inhibiting gluconeogenesis in the liver.

Olive Component Oleuropein Promotes ß-Cell Insulin Secretion and Protects ß-Cells from Amylin Amyloid-Induced Cytotoxicity.

Oleuropein, a natural product derived from olive leaves, has reported anti-diabetic functions. However, detailed molecular mechanisms for how it affects ß-cell functions remain poorly understood. Here, we present evidence that oleuropein promotes glucose-stimulated insulin secretion (GSIS) in ß-cells. The effect is dose-dependent and stimulates the ERK/MAPK signaling pathway. We further demonstrated that oleuropein inhibits the cytotoxicity induced by amylin amyloids, a hallmark feature of type 2 diabetes. We demonstrated that these dual functions are structure-specific: we identified the 3-hydroxytyrosol moiety of oleuropein as the main functional entity responsible for amyloid inhibition, but the novel GSIS function requires the entire structure scaffold of the molecule.

Beta Cell Function and the Nutritional State: Dietary Factors that Influence Insulin Secretion.

Approximately 366 million people worldwide have been diagnosed with type-2 diabetes (T2D). Chronic insulin resistance, decreased functional ß-cell mass, and elevated blood glucose are defining characteristics of T2D. Great advances have been made in understanding the pathogenesis of T2D with respect to the effects of dietary macronutrient composition and energy intake on ß-cell physiology and glucose homeostasis. It has been further established that obesity is a leading pathogenic factor for developing insulin resistance. However, insulin resistance may not progress to T2D unless ß-cells are unable to secret an adequate amount of insulin to compensate for decreased insulin sensitivity. Therefore, pancreatic ß-cell dysfunction plays an important role in the development of overt diabetes. This paper reviews recent research findings on the effects of several micronutrients (zinc, vitamin D, iron, vitamin A), leucine, and the phytochemical, genistein on pancreatic ß-cell physiology with emphasis on their effects on insulin secretion, specifically in the context of T2D.

Neuropeptide Y promotes adipogenesis in chicken adipose cells in vitro.

Neuropeptide Y is an evolutionarily conserved neurotransmitter that stimulates food intake in higher vertebrate species and promotes adipogenesis in mammals. The objective of this study was to determine if NPY also enhances adipogenesis in birds, using chickens as a model. The stromal-vascular fraction of cells was isolated from the abdominal fat of 14 day-old broiler chicks and effects of exogenous chicken NPY on proliferation and differentiation determined. Based on a thymidine analog incorporation assay and gene expression analysis, there was no effect of NPY on proliferation during the first 12 hours post-treatment in cells that were induced to proliferate. However, there were effects of NPY treatment on proliferation and lipid accumulation during the first 6 days post-induction of differentiation. Neuropeptide Y supplementation during induction of differentiation was associated with greater glycerol-3-phosphate dehydrogenase activity and staining for neutral lipids, indicative of augmented lipid accumulation. This was also accompanied by increased proliferation during differentiation, which was characterized by up-regulation of proliferation and preadipocyte marker mRNA, and a greater number of proliferating cells in groups that were treated with NPY. Additionally, NPY treatment was associated with increased expression of fatty acid binding protein 4 and lipoprotein lipase during differentiation. In conclusion, these results suggest that NPY plays a role in promoting adipogenesis in chickens and that the mechanisms involve an increase in the synthesis of new preadipocytes and increased lipid synthesis and storage.

IL-17 plays a central role in initiating experimental Candida albicans infection in mouse corneas.

The pathogenesis of fungal infection in the cornea remains largely unclear. To understand how the immune system influences the progression of fungal infection in corneas, we inoculated immunocompetent BALB/c mice, neutrophil- or CD4⁺ T-cell-depleted BALB/c mice, and nude mice with Candida albicans. We found that only immunocompetent BALB/c mice developed typical Candida keratitis (CaK), while the other mouse strains lacked obvious clinical manifestations. Furthermore, CaK development was blocked in immunocompetent mice treated with anti-IL-17A or anti-IL-23p19 to neutralize IL-17 activity. However, no significant effects were observed when Treg cells, γδ T cells, or IFN-γ were immunodepleted. Upon infection, the corneas of BALB/c mice were infiltrated with IL-17-producing leukocytes, including neutrophils and, to a lesser degree, CD4⁺ T cells. In contrast, leukocyte recruitment to corneas was significantly diminished in nude mice. Indeed, nude mice produced much less chemokines (e.g. CXCL1, CXCL2, CXCL10, CXCL12, CCL2, and IL-6) in response to inoculation. Remarkably, addition of CXCL2 during inoculation restored CaK induction in nude mice. In contrast to its therapeutic effect on CaK, neutralization of IL-17 exacerbated Candida-induced dermatitis in skin. We conclude that IL-17, mainly produced by neutrophils and CD4⁺ T cells in the corneas, is essential in the pathogenesis of CaK.

The flavonoid luteolin induces nitric oxide production and arterial relaxation.

PURPOSE: Luteolin, a flavone present in many foods and medicinal plants, may have beneficial effects on various human chronic diseases. In the present study, we investigated the hypothesis that luteolin can directly act on vascular endothelial cells (ECs), leading to nitric oxide (NO) production and subsequent vascular relaxation. METHODS: Rat aortic rings were mounted in organ bath. Luteolin was added cumulatively, and vessel relaxation of rat aortic rings precontracted with phenylephrine (PE) or potassium was recorded. Endothelial nitric oxide synthase (eNOS) phosphorylation at Ser1177 and NO production from aortic rings and primary human aortic endothelial cells (HAECs) exposed to luteolin were measured by using Western blot and fluorometric assay, respectively. RESULTS: Luteolin dose-dependently (10-100 µmol/L) elicited relaxation of PE- or potassium-contracted aortic rings. The vasorelaxation effect of luteolin was attenuated by the eNOS inhibitor, N-nitro-L-arginine methyl ester, suggesting that this luteolin action is at least partially mediated by activating eNOS activity. We further found that luteolin dose-dependently (10-100 µmol/L) increased eNOS phosphorylation at Ser1177 (up to 1.9-fold) in isolated rat rings. Consistently, exposure of HAECs to luteolin also increased eNOS phosphorylation and NO production. CONCLUSIONS: Luteolin may be a vascular protective agent by directly acting on vascular ECs to stimulate NO-dependent vascular dilatation.

Sulforaphane Ameliorates High-Fat-Diet-Induced Metabolic Abnormalities in Young and Middle-Aged Obese Male Mice.

Type 2 diabetes (T2D) is still a fast-growing health problem globally. It is evident that chronic insulin resistance (IR) and progressive loss of ß-cell mass and function are key features of T2D etiology. Obesity is a leading pathogenic factor for developing IR. The aim of the present study was to determine whether sulforaphane (SFN), a natural compound derived from cruciferous vegetables, can prevent (prevention approach) or treat (treatment approach) obesity and IR in mouse models. We show that dietary intake of SFN (0.5 g/kg of HFD) for 20 weeks suppressed high-fat diet (HFD)-induced fat accumulation by 6.04% and improved insulin sensitivity by 23.66% in young male mice. Similarly, dietary provision of SFN (0.25 g/kg) significantly improved blood lipid profile, glucose tolerance, and insulin sensitivity of the middle-aged male mice while it had little effects on body composition as compared with the HFD group. In the treatment study, oral administration of SFN (40 mg/kg) induced weight loss and improved insulin sensitivity and plasma lipid profile in the diet-induced-obesity (DIO) male mice. In all three studies, the metabolic effects of SFN administration were not associated with changes in food intake. In vitro, SFN increased glucose uptake in C2C12 myotubes and increased fatty acid and pyruvate oxidation in primary human skeletal muscle cells. Our results suggest that SFN may be a naturally occurring insulin-sensitizing agent that is capable of improving the metabolic processes in HFD-induced obesity and IR and thereby may be a promising compound for T2D prevention.

Oleuropein has hypophagic effects in broiler chicks.

Oleuropein, a phenolic compound derived from olives, has known glucoregulatory effects in mammalian models but effects in birds are unknown. We investigated effects of dietary supplementation and exogenous administration of oleuropein on broiler chick feed intake and glucose homeostasis during the first 7 days post-hatch. One hundred and forty-eight day-of-hatch broiler chicks were randomly allocated to one of four dietary treatments with varying oleuropein concentrations (0, 250, 500, or 1,000 mg/kg). Body weight and breast muscle and liver weights were recorded on day 7. In the next experiment, chicks received intraperitoneal (IP) injections of oleuropein at doses of 0 (vehicle), 50, 100, or 200 mg/kg on day 4 post-hatch, with feed intake and blood glucose levels measured thereafter. Lastly, chicks fed a control diet were fasted and administered intracerebroventricular (ICV) injections of oleuropein at doses of 0, 50, 100, or 200 µg, after which feed intake was recorded. Results indicated that IP and ICV injections led to decreased feed intake, primarily at 60 min post-injection, with effects diminishing by 90 min in the IP study. Blood glucose levels decreased 1-h post-IP injection at higher oleuropein doses. These findings suggest that oleuropein acts as a mild appetite suppressant and influences energy metabolism in broiler chickens.

Low-dose of phenolic rich extract from Annona squamosa Linn leaves ameliorates insulin sensitivity and reduces body weight gain in HF diet-induced obesity.

Obesity is associated with metabolic abnormalities that increase the risk and severity of several diseases. This study aimed to explore whether the aqueous extract of Annona squamosa Linn leaves (ASE) can ameliorate metabolic abnormalities associated with high fat (HF) diet-induced obesity. Forty-eight male Wistar rats were distributed among four treatment groups: a standard low-fat diet group, a HF diet group, and two HF diet groups with a daily oral dose of ASE (100 or 200 mg/kg body weights) administered for 9 weeks. Daily energy intake, body weight, blood glucose levels and glucose tolerance, and insulin tolerance were evaluated. At the end of the study, organs, and tissues were collected and weighed for analysis, and blood samples were collected to determine the serum insulin levels and serum liver enzymes. Total phenolic and flavonoid contents and 2,2-Diphenyl-1-picrylhydrazyl free radical antioxidant activity of the ASE were evaluated. Oral administration of the low dose of ASE to HF diet-fed rats significantly reduced the long-term food intake and body weight gain without altering adiposity compared with untreated HF diet-fed rats. This outcome was accompanied by a significant improvement in insulin sensitivity and a reduction in fasting blood glucose (FBG) levels measured at weeks 6 and 9 of the study. The high dose of ASE had a short-term effect on body weight gain and food and caloric intake, and in the long-term, it improved FBG levels measured at weeks 6 and 9 of the study. The high dose of ASE resulted in hyperinsulinemia and high homeostatic model assessment for insulin resistance (HOMA-IR) value compared to healthy rats. Total phenolic and flavonoid contents were 74.9 ± 0.491 mg of gallic acid equivalent and 20.0 ± 0.091 mg quercetin equivalent per g of ASE, respectively. The antioxidant activity of ASE expressed as half-maximal inhibitory concentration (IC50) value was 8.43 ± 0.825 mg/mL. These data suggest that ASE can safely and potently reduce the development of insulin resistance induced by HF diet feeding and lowering body weight gain in a dose-dependent manner.

Date (Phoenix dactylifera L.) seed oil is an agro-industrial waste with biopreservative effects and antimicrobial activity.

Antimicrobial resistant (AMR) infections are a leading health threat globally. Previous literature has underscored the farm-to-fork continuum as a potential focal point for the emergence and spread of AMR. In the present study, date (Phoenix dactylifera L.) seed oil was investigated for its chemical composition and antimicrobial activity against common foodborne pathogens including Escherichia coli O157:H7, Salmonella enteritidis, Salmonella typhimurium, Listeria monocytogenes, and Staphylococcus aureus in vitro, and in ultra-high-temperature (UHT) milk as a food model at storage temperatures of 37 °C (24 h) and 10 °C (7 days). GC-MS analysis of the seed oil revealed 20 compounds, with octadecane (52.2-55.4%) as the major constituent, and the fatty acid analysis revealed 17 fatty acids, with oleic acid (42.3-43.1%) as the main constituent, followed by lauric acid (19.8-20.3%). The antimicrobial activity of date seed oil was determined using the microdilution method. A significant inhibition against gram-negative bacteria was noted in microbiological media and UHT milk, with a log reduction ranging from 4.3 to 6.7 (at 37 °C/24 h) and 5.7 to 7.2 (at 10 °C/7 days), respectively, at oil concentrations ranging between 10 and 15 µl/ml. The oil showed a similar significant inhibitory effect against St. aureus in the microbiological media (2.0-6.0 log reduction), whereas the inhibitory effect against L. monocytogenes was not statistically significant, with a maximum log reduction of 0.64 achieved at a concentration of 10 µl/ml. AFM imaging of the bacteria showed that oil treatment led to morphological changes in the bacteria including the formation of distorted shapes, surface blebs, indentations, stiffness, and swelling. Present findings suggest that date seed oil can be a promising by-product with potential antimicrobial activity and a food preservative.