Comprehensive Chemical Profiling and Mechanistic Insight into Anticancer Activity of Annona muricata Leaves Extract.

The aqueous extract of Annona muricata L. leaves was thoroughly analyzed using the UPLC-MS/MS, in addition to a new approach of examination of the extract's impact on cancer of EAC(Ehrlich ascites carcinoma) in albino male mice. The aim was to investigate the diversity of the phytochemical constituents of the aqueous leaf capsule extract and their impacts on EAC as anticancer agents. The UPLC-ESI-MS/MS screening resulted in 410 tentatively identified metabolites. Among them, 384 compounds were tentatively identified in a previous study, besides a number of 26 compounds belonging to acetogenins, phenolics, flavonoids, alkaloids, and other miscellaneous compounds, which were exclusively identified in the aqueous extract of the leaf capsule. Interestingly, a new compound was tentatively characterized as galloyl-quinic acid-rutinoside. This study also demonstrated that treating EAC mice with an extract from A. muricata leaves significantly improved the abnormalities in the expression of pro-apoptotic (Bax and caspase-3) and anti-apoptotic (Bcl-2) genes. Furthermore, the extract showed good protection against induced Ehrlich hepatocarcinoma, according to the microscopical, histological, and immune-histochemical analyses of the liver tissues and tumor mass.

LCMS/MS Phytochemical Profiling, Molecular, Pathological, and Immune-Histochemical Studies on the Anticancer Properties of Annona muricata.

Annona muricate is a tropical plant that is well-known for its edible fruit of therapeutic interest. LCMS/MS analyses were applied to identify phytoconstituents of the ethanolic extract of the whole fruits and the aqueous extract of the edible fruit part, in addition to the investigation of their anticancer properties against Ehrlich ascites carcinoma (EAC) in male albino mice. LCMS/MS analyses resulted in the identification of 388 components, representing a wide array of classes of compounds, including acetogenins as the major constituents, alkaloids, flavonoids, and phenolics. Among them, four compounds were tentatively characterized as new compounds (1-4), including an acid derivative, protocatechuic-coumaroyl-quinic acid (1), and three flavonoid derivatives, dihydromyricetin galloyl hexoside (2), apigenin gallate (3), and dihydromyricetin hexouronic acid hexoside (4). Induction with EAC cells resulted in abnormalities in the gene expression of pro-apoptotic genes (Bax and caspase-3) and anti-apoptotic gene (Bcl-2) in the tumor mass. Moreover, microscopic, histopathological, and immune-histochemical examinations of the tumor mass and liver tissues exhibited extensive growth of malignant Ehrlich carcinoma cells and marked hydropic degeneration of hepatocytes and infiltration by tumor cells to liver tissue with marked inflammatory reaction. These abnormalities were markedly ameliorated aftertreatment of EAC mice with A. muricata extracts.

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.

Influence of Marek's disease virus vaccines on chicken melanoma differentiation-associated gene 5-dependent-type I interferon signal transduction pathway with a highlight on their secondary impact on the immune responses post Newcastle disease virus vaccination.

Marek's disease virus (MDV) leads to a lytic infection of B-lymphocytes in chickens, and also latently infects T-lymphocytes. Although Marek's disease vaccines have been widely in use, little is known about the innate immune response of this important livestock vaccine. In this study, we tested the effect of different commercially applied Marek's disease vaccines on the expression pattern of selected genes related to chicken interferon-alpha (chIFN-α) (melanoma differentiation associated gene 5 "MDA5″ dependent) signal transduction pathway. Both MDV serotype I (Rispens) and serotype III (Herpesvirus of turkey "HVT") vaccines could stimulate MDA5 dependent-type I interferon response as early as three days post vaccination in a dose-dependent manner. The stimulation continued up to 10 days in the instance of HVT vaccine and declined in the case of Rispens. Surprisingly, increasing the doses of the two vaccines led to dose-dependent down-regulation in the expression pattern of the investigated pathway, five and ten days post vaccination. Additionally, to shed the light on the consequent effect on the immune responses of the other viral vaccine, another experimental model based on Newcastle disease virus (NDV) vaccines was designed using HVT, HVT-VP2 and Rispens MDV vaccines. The three MDV vaccines were found to reduce chicken humoral immune response post NDV vaccination. However, only Rispens and HVT-VP2 had suppressive effects on the expression of MDA5-dependent-chIFN-α related cytokines. Consistent with this finding, the protection rate and NDV- humoral immune response post challenge with virulent NDV strain was lower in case of Rispens and HVT-VP2 vaccines.