The study of wound healing activity of Thespesia populnea L. bark, an approach for accelerating healing through nanoparticles and isolation of main active constituents.

The present study provides an evaluation for the wound healing activity of the ethanolic extract of Thespesia populnea L. bark (EBE) and its successive fractions in two doses level (1&2%), designed for determining the most bioactive fraction and the suitable dose. Furthermore, development of the most convenient formulation for these bioactive fractions through either their direct incorporation into hydrogel formulations or incorporation of chitosan-loaded nanoparticles with these bioactive fractions into hydrogel formulations. The highest excision wound healing activity was observed in petroleum ether (Pet-B) followed by ethyl acetate (Etac-B) fractions at the high dose (2%). The most suitable formulation designed for the Etac-B fraction was found to be the chitosan-loaded nanoparticles incorporated in the hydrogel formulation, while the conventional hydrogel formulation was observed to be the highly acceptable formulation for Pet-B fraction. Further phytochemical studies of the bioactive fractions led to the isolation of many compounds of different chemical classes viz; beta-sitosterol and lupeol acetate isolated from the Pet-B, in addition to cyanidin and delphinidin from the Etac-B. Our results revealed that EBE and its bioactive fractions (Pet-B & Etac-B) could be considered as strong wound healers through their anti-oxidant and anti-inflammatory activities, in addition to stimulating collagen synthesis.

Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood-testis barrier remodeling.

This study aimed to investigate the effects of eugenol treatment on reproductive parameters in acrylamide (ACR)-intoxicated rats. The study evaluated alterations in relative testes and epididymides weights, sperm quality, serum hormonal status, seminal plasma amino acids, testicular cell energy and phospholipids content, oxidative and nitrosative stress parameters, adenosine monophosphate-activated protein kinase/ phosphoinositide 3-kinase/phosphor-protein kinase B/mammalian target of rapamycin (AMPK/PI3K/p-AKT/mTOR) signaling pathway, blood-testis barrier (BTB) remodeling markers, testicular autophagy and apoptotic markers, as well as histopathological alterations in testicular tissues. The results revealed that eugenol treatment demonstrated a significant improvement in sperm quality parameters, with increased sperm cell concentration, progressive motility live sperm, and a reduction in abnormal sperm, compared to the ACR-intoxicated group. Furthermore, eugenol administration increased the levels of seminal plasma amino acids in a dose-dependent manner. In addition, eugenol treatment dose-dependently improved testicular oxidative/nitrosative stress biomarkers by increasing oxidized and reduced glutathione levels and reducing malondialdehyde and nitric oxide contents as compared to ACRgroup. However, eugenol treatment at a high dose restored the expression of AMPK, PI3K, and mTOR genes, to levels comparable to the control group, while significantly increasing p-AKT content compared to the ACRgroup. In conclusion, the obtained findings suggest the potential of eugenol as a therapeutic agent in mitigating ACR-induced detrimental effects on the male reproductive system via amelioration of ROS-mediated autophagy, apoptosis, AMPK/p-AKT/mTOR signaling pathways and BTB remodeling.

Neurological study on the effect of CeNPs and/or La Cl3 on adult male albino rats.

Lanthanides are a group of 15 elements (8 heavy and 7 light) grouped for their proximity in the chemical and physical properties. Recently, this group of elements has received great attention because of their importance, and their entrance into many industrial technologies making the probability of the living organisms' exposure to it increase. The present study aims to study ability of cerium nanoparticles (CeNPs) or lanthanum (LaCl3) to cross the blood brain barrier also, investigate their neuro effect separately or together on some parameters in six brain areas (cortex, cerebellum, hippocampus, striatum, midbrain, and hypothalamus) of the adult male albino rats. The results showed the ability of both elements to distribute and accumulate in the different brain areas. Also, the results of CeNPs or LaCl3 treatment were in the same line where each element caused a significant decrease in norepinephrine (NE), dopamine (DA), serotonin (5-HT) and GABA accompanied with a significant increase in 5- hydroxyl indoleacetic acid (5-HIAA) glucose level. On the other hand, GSH and MDA showed a significant decrease after CeNPs treatment while, with LaCl3 treatment, MDA showed a significant increase in the different brain areas after 3 weeks of treatment. The coadministration of CeNPs and La Cl3 caused an ameliorating effect in all the tested parameters. In conclusion, from the previous studies the effects of lanthanides in the present study may be in part due to its effect on the release or turnover of neurotransmitters and insulin secretion. Finally, the ameliorative effect of CeNPs may be regarded as its high activity to scavenge the free radicals.

Lactiplantibacillus plantarum and Saussurea costus as Therapeutic Agents against a Diabetic Rat Model-Approaches to Investigate Pharmacophore Modeling of Human IkB Kinase and Molecular Interaction with Dehydrocostus Lactone of Saussurea costus.

Lactic acid bacteria is well-known as a vital strategy to alleviate or prevent diabetes. Similarly, the plant Saussurea costus (Falc) Lipsch is a preventive power against diabetes. Here, we aimed to determine whether lactic acid bacteria or Saussurea costus is more effective in treating a diabetic rat model in a comparative study manner. An in vivo experiment was conducted to test the therapeutic activity of Lactiplantibacillus plantarum (MW719476.1) and S. costus plants against an alloxan-induced diabetic rat model. Molecular, biochemical, and histological analyses were investigated to evaluate the therapeutic characteristics of different treatments. The high dose of S. costus revealed the best downregulated expression for the IKBKB, IKBKG, NfkB1, IL-17A, IL-6, IL-17F, IL-1ß, TNF-α, TRAF6, and MAPK genes compared to Lactiplantibacillus plantarum and the control groups. The downregulation of IKBKB by S. costus could be attributed to dehydrocostus lactone as an active compound with proposed antidiabetic activity. So, we performed another pharmacophore modeling analysis to test the possible interaction between human IkB kinase beta protein and dehydrocostus lactone as an antidiabetic drug. Molecular docking and MD simulation data confirmed the interaction between human IkB kinase beta protein and dehydrocostus lactone as a possible drug. The target genes are important in regulating type 2 diabetes mellitus signaling, lipid and atherosclerosis signaling, NF-κB signaling, and IL-17 signaling pathways. In conclusion, the S. costus plant could be a promising source of novel therapeutic agents for treating diabetes and its complications. Dehydrocostus lactone caused the ameliorative effect of S. costus by its interaction with human IkB kinase beta protein. Further, future studies could be conducted to find the clinical efficacy of dehydrocostus lactone.

Chrysin loaded nanovesicles ameliorated diabetic peripheral neuropathy. Role of NGF/AKT/GSK-3ß pathway.

Diabetic peripheral neuropathy (DPN) is a common diabetic complication. Chrysin (CHY) has many biological properties but poor oral bioavailability. This study investigates the effect of CHY and CHY-loaded nanovesicles (CHY-NVs) on streptozotocin (STZ)-induced DPN in rats. CHY-NVs were prepared by using film hydration method. The formula with the best entrapment efficiency%, lowest particle size, highest zeta potential, and highest in vitro CHY released profile was selected, characterized by Differential scanning calorimetry, Fourier transformation infrared spectroscopy analysis, and examined by Transmission electron microscope. Acute toxicity test, pharmacokinetic study and experimental model of diabetes mellitus were performed on the selected formulation. Wistar rats were considered diabetic by administration of a single intraperitoneal dose of STZ (50 mg/kg). 48 h after STZ administration, hyperglycemic rats were randomly assigned into four groups, one group of untreated hyperglycemic rats and the other three groups received daily oral doses of unloaded NVs, CHY-NVs (25 mg/kg), and CHY-NVs (50 mg/kg), respectively for 21 days. Moreover, five additional groups of healthy rats received: distilled water (control), free CHY, unloaded NVs, and CHY-NVs respectively for 21 days. CHY and CHY-NVs maintained body weight and reduced STZ-induced behavioral changes in rotarod, hind paw cold allodynia, tail cold allodynia, tail flick, and hot plate tests. CHY and CHY-NVs lowered blood glucose, glycated hemoglobin, elevated serum reduced glutathione (GSH), and reduced plasma malondialdehyde (MDA) levels. CHY-NVs elevated phosphatidylinositol 3-kinase (Pi3k), phosphorylated protein kinase B (p-AKT), and reduced nuclear factor kappa B (NF-κB), interleukin-6 (IL-6) in sciatic nerve homogenate. CHY and CHY-NVs increased nerve growth factor (NGF) and decreased glycogen synthase kinase-3ß (GSK-3ß) gene expressions in the sciatic nerve. In conclusion, CHY and CHY-NVs ameliorated STZ-induced DPN behavioral and histopathological changes via attenuating hyperglycemia, exerting anti-oxidant, anti-inflammatory effects, activating NGF/p-AKT/GSK-3ß pathway, and its anti-apoptotic effect. The best pharmacokinetic profile and therapeutic effect was observed in rats treated with CHY-loaded NVs.

Lipopolysaccharide induced neuroprotective effects of bacterial protease against Alzheimer's disease in male Wistar albino rats.

Alzheimer's disease (AD) is a highly severe neurodegenerative condition that affects the hippocampus and is characterized by memory loss and dementia. This investigation aims to determine the potential of a bacterial protease enzyme produced by a new mutant strain of bacteria (Bacillus cereus S6-3/UM90) to influence the rat behavioural, biochemical, histological, and immuno-histochemical functions induced by lipopolysaccharides (LPS) experimentally. The administration of LPS exhibited a decline in memory performance via Morris' Water Maze test along with an elevation of IL-6, IL-17, amino acid neurotransmitters, Adenosine monophosphate (AMP), and 8-OHdG, whereas a decrease in ATP (Adenosine Triphosphate), monoamine transmitters, AChE (acetylcholinesterase) and PC (phosphatidylcholine). Additionally, there was a notable increase in GFAP (glial fibrillary acidic protein) and p-Tau protein immuno-expression levels along with obvious histological lesions in the hippocampal CA3 region. Moreover, the administration of protease or Donepezil restored the measured parameters to nearly normal levels and improved the histological architecture of the hippocampus and ameliorated memory impairments. In conclusion, the study provides evidence that the treatment with Bacterial protease can improve the memory and learning impairments of LPS-induced AD and may be used as a promising therapeutic agent to manage AD since it has anti-inflammatory and antioxidant effects.

Curcumin-resveratrol nano-formulation counteracting hyperammonemia in rats.

Malnutrition and low dietary protein intake could be risk factors for developing peripheral and central hyperammonemia, especially in pediatrics. Both curcumin and resveratrol proved to be effective against several hepatic and cerebral injuries. They were reported to be beneficial in lowering circulating ammonia levels, yet both are known for their low bioavailability. The use of pharmaceutical nano-formulations as delivery systems for these two nutraceuticals could solve the aforementioned problem. Hence, the present study aimed to investigate the valuable outcome of using a combination of curcumin and resveratrol in a nanoemulsion formulation, to counteract protein-deficient diet (PDD)-induced hyperammonemia and the consequent complications in male albino rats. Results revealed that using a nanoemulsion containing both curcumin and resveratrol at a dose of (5 + 5 mg/kg) effectively reduced hepatic and brain ammonia levels, serum ALT and AST levels, hepatic and brain nitric oxide levels, oxidative DNA damage as well as disrupted cellular energy performance. In addition, there was a substantial increase in brain levels of monoamines, and a decrease in glutamate content. Therefore, it can be concluded that the use of combined curcumin and resveratrol nanoemulsion is an effective means of ameliorating the hepatic and cerebral adverse effects resulting from PDD-induced hyperammonemia in rats.

Intranasal ondansetron microemulsion counteracting the adverse effects of cisplatin: animal study.

BACKGROUND: Cisplatin is considered one of the most effective and commonly used chemotherapeutic drugs, but despite its high therapeutic effectiveness, most patients treated with cisplatin suffer from nausea and vomiting, neurotoxic side effects, and cerebral psychiatric disorders such as depression. Therefore, the aim of the current work was to explore whether a selective 5-HT3 receptor antagonist (Ondansetron) administered via the oral route or intranasally in microemulsion form would alleviate cisplatin's adverse effects. METHODS: The selected ondansetron microemulsion was characterized in vitro for particle size, polydispersity, zeta potential, morphology, and nasal permeation, and in vivo in terms of anti-emetic and antidepressant activity, with the assessment of biochemical markers in brain homogenates. RESULTS: Results revealed that both orally administered ondansetron and intranasally administered microemulsion were able to counteract the pica effect by increasing food consumption, water intake, and decreasing kaolin intake. They were also able to increase BDNF, normalize IL-6, increase serotonin, and normalize NOx, MDA, GSSH/GSH as well as 8OHdG levels in rats' brain homogenates. The intranasal ondansetron microemulsion displayed superiority compared to oral conventional ondansetron in terms of increasing food intake, reduction of stomach content, and normalization of serotonin turnover. CONCLUSION: Ondansetron microemulsion can be administered by an alternative route of administration (intranasal) rather than oral, for patients on cisplatin chemotherapy.

Dietary Supplementation of Silybum marianum Seeds Improved Growth Performance and Upregulated Associated Gene Expression of Muscovy Ducklings (Cairina moschata).

The effect of feeding on diets supplemented with Silybum marianum L. dry seeds (SMS) on growth performance, mortality percentage, biochemical parameters, the expression profile of related genes, and genotoxic effect in Muscovy ducklings was evaluated during a brooding period of 4 weeks. Two hundred and forty one-day-old Muscovy ducks were randomly assigned to four treatment groups (60 ducklings/group), the first group fed on basal diet with no additives (control), and the second (4 g kg-1), third (8 g kg-1), and fourth (12 g kg-1) groups fed the basal diet supplemented with 0, 4, 8, and 12 g kg-1 diet SMS, respectively. A substantial improvement in live body weight (LBW), body weight gain (BWG), and growth rate (GR), and a decrease in feed conversion ratios (FCR) and mortality rate were shown in ducks fed a diet supplemented with either 8 g kg-1 or 12 g kg-1 SMS compared to the other groups. Relevant improvements in liver function, oxidative stress markers, purinergic cell energy, and brain appetite were recorded on ducklings fed diets supplemented with SMS. Moreover, diets which included 8 or 12 g kg-1 SMS positively upregulated the expression of growth hormone gene (GH) and antioxidant genes (SOD1, SOD2, and CAT). These results are consistent with the increase in liver activity SOD and CAT enzymes, resulting in less DNA fragmentation. Consequently, all the aforementioned improvements in biochemical parameters and gene expression profiling may explain the superiority of the treated ducklings compared with the control group. Conclusively, the SMS could be used as a natural feed additive to promote health status and improve the growth performance of small grower ducks during the brooding period.

Baicalin lipid nanocapsules for treatment of glioma: characterization, mechanistic cytotoxicity, and pharmacokinetic evaluation.

OBJECTIVES: Baicalin is a promising anticancer nutraceutical compound, but its application is hindered by its low water solubility and bioavailability, which can be remedied by its encapsulation in nanoparticles. METHODS: Lipid nanocapsules (LNCs) were developed to enhance baicalin delivery via intravenous and intranasal routes, and potentiate its therapeutic activity in treatment of glioma. RESULTS: LNCs displayed a particle size of 17.76 nm and sustained release of 74.36% after 24 h. The IC50 of baicalin LNCs (13 ± 5 µg/ml) was 60 times lower than free baicalin (780 ± 107 µg/ml) on human glioblastoma multiform cell line U87, with adequate cellular uptake as delineated by confocal laser microscopy. Both baicalin and LNCs induced cell cycle arrest at S and G2/M phases, with significant up-regulation in P21 gene, and decline in Nrf-2, HO-1 and VEGF gene expression. LNCs increased baicalin's bioavailability, either after intravenous (AUC0-24 h 10.94 ± 0.28 vs 3.53 ± 0.09 µg/ml*h), or intranasal administration (AUC0-24 h 6.26 ± 0.11 vs 3.17 ± 0.04 µg/ml*h). They also bypassed the blood brain barrier and achieved significantly higher brain delivery compared to free baicalin (drug targeting efficiency 160.73% vs 52.9%). CONCLUSION: Baicalin LNCs is a promising treatment modality for glioma, when administered through intravenous or intranasal routes.

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats.

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF-MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract's effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF-MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress.

Combating hematopoietic and hepatocellular abnormalities resulting from administration of cisplatin: role of liver targeted glycyrrhetinic acid nanoliposomes loaded with amino acids.

The effectiveness of cisplatin in cancer treatment renders its use vital to clinicians. However, the accompanying side effects as cachexia, emesis and liver damage necessitate the use of a dietary supplement which is capable of hindering such undesirable complications. The branched chain amino acids as well as glutamine and arginine have been proven to be effective nutritional co-adjuvant therapeutic agents. Furthermore, new pharmaceutical approaches encompass designing organ-targeted nanoformulations to increase the medicinal efficacy. Therefore, the aim of the present study was to investigate the beneficial effects of liver-targeted amino acids-loaded nanoliposomes in counteracting the adverse hematopoietic and hepatic complications associated with cisplatin. Results revealed the use of the combination of two nanoliposomal formulations (one loading leucine + isolecuine + valine, and the other loading glutamine and arginine) given orally at a dose of 200 mg/kg for twelve days was effective against cisplatin-induced toxicities represented by improvement in the complete blood picture parameters, decrease in the serum hepatic enzymes levels, amelioration of the hepatic oxidative stress and cellular energy imbalance along with reduction in the histopathological abnormalities. It can be concluded that amino acids loaded nanoliposomes could be considered a new strategy in preventing cisplatin's adverse effects.

Curcumin nanoemulsion counteracts hepatic and cardiac complications associated with high-fat/high-fructose diet in rats.

The relationship between the incidence of cardiovascular abnormalities and non-alcoholic fatty liver disease (NAFLD) has long been postulated. Curcumin (CUR) is a potential anti-atherosclerotic agent but its poor water solubility hinders its pharmacological use. Therefore, the present study aimed to investigate the effect of formulation of CUR nanoemulsion prepared using the spontaneous emulsification technique on high fat high fructose (HFHF)-induced hepatic and cardiac complications. Fifty Wistar rats were divided into five groups. CUR nanoemulsion at doses of 5 and 10 mg/kg and conventional powdered CUR at a dose of 50 mg/kg were orally administered daily to rats for two weeks, and compared with normal control and HFHF control. Results revealed that the high dose level of CUR nanoemulsion was superior to conventional CUR in ameliorating the HFHF-induced insulin resistance status and hyperlipidemia, with beneficial impact on rats' recorded electrocardiogram (ECG), serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels, leptin, adiponectin, creatine phosphokinase, lactate dehydrogenase and cardiac troponin-I. In addition, hepatic and cardiac oxidative and nitrosative stresses, oxidative DNA damage and disrupted cellular energy statuses were counteracted. Results were also confirmed by histopathological examination. PRACTICAL APPLICATIONS: The use of curcumin nanoemulsion could be beneficial in combating hepatic and cardiac complications resulting from HFHF diets.

Muscle oxidative stability, fatty acid and amino acid profiles, and carcass traits of broiler chickens in comparison to spent laying hens.

This research compared muscle oxidative stability, meat composition, and carcass traits in commercial broilers and spent laying hens. At week 65 of age, 40 ISA Brown laying hens were randomly selected to create 10 replicate cages (4 birds per cage). Also, 60 day-old Ross chicks were equally divided into six replicates (10 chicks each). Broiler chickens had a higher dressing percentage than spent hens (P = 0.027), but a lower abdominal fat percentage (P = 0.009). Spent hens had higher level of malondialdehyde (MDA) in the breast muscles (P = 0.001). Meanwhile, the MDA levels in thigh muscles did not differ in both groups (P = 0.328). Broiler chickens showed greater concentrations of saturated fatty acids (palmitic and stearic) in the breast (P = 0.012 and 0.006, respectively) and thigh (P = 0.033 and 0.038, respectively) muscles as compared to spent hens. Meanwhile, broiler chickens had lower concentrations of palmitoleic, oleic and eicosapentaenoic in the breast muscles (P = 0.002, 0.004 and 0.001, respectively). Also, spent hens had greater concentrations of linoleic in the breast and thigh muscles (P = 0.018 and 0.035, respectively). When compared to broiler chickens, spent hens had greater essential amino acids (isoleucine, methionine and tyrosine) concentrations in the breast muscles (P = 0.002, 0.001 and 0.036, respectively). Finally, while broiler chickens had superior carcass traits, spent hens showed better meat composition (higher polyunsaturated fatty acids and essential amino acids). Furthermore, the oxidative stability of the breast muscles of spent hens was lower than that of broilers. Spent hens can be used as an attractive source of chicken meat if certain precautions are adopted.

Anticancer and Neuroprotective Activities of Ethyl Acetate Fractions from Morus macroura Miq. Plant Organs with Ultraperformance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Profiling.

Column chromatography afforded the isolation of seven secondary metabolites (1-(2,4,6-trihydroxy phenyl)-ethanone-4-O-ß-d-glucopyranoside, naringenin-7-O-ß-d-glucopyranoside, kaempferol-3-O-α-l-rhamnoside, kaempferol-3-O-ß-d-glucopyranoside, quercetin-3-O-ß-d-glucopyranoside, quercetin-3-O-ß-d-galactopyranoside, rutin) from the ethyl acetate (ET) fractions of Morus macroura Miq. stems (S), leaves (L), and fruits (F). Their identification based on ultraviolet (UV), electron ionization (EI), electrospray ionization-mass spectrometry (ESI-MS), and 1D and 2D NMR data. In addition, profiling of ET fractions using ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) resulted in the identification of 82 compounds belonging to different classes, mainly polyphenolic constituents. Chemical profiling as well as molecular docking directed us to biological evaluation. Interestingly, the ET-L fraction exhibited a robust cytotoxic activity against HepG-2, MCF-7, and HELA cell lines. Also, it displayed a neuromodulatory activity against cisplatin neurotoxicity in rats by ameliorating the neurobehavioral dysfunction visualized in the open field and Y-maze test and modulating the neurochemical parameters such as brain amino acid levels (glutamate, aspartate, serine, and histidine), oxidative stress markers (GSH, MDA, and 8-hydroxy-2'-deoxyguanosine), and purinergic cell energy (adenosine triphosphate (ATP) and adenosine monophosphate (AMP)). In conclusion, the isolated compounds (kaempferol-3-O-ß-glucoside and quercetin-3-O-ß-glucoside) from the ET-L fraction could serve as potent anticancer agents due to their strong antioxidant, in vitro cytotoxicity, and in vivo neuroprotective activity.

Chemical profiles with cardioprotective and anti-depressive effects of Morus macroura Miq. leaves and stem branches dichloromethane fractions on isoprenaline induced post-MI depression.

This study was conducted to explore the potential cardioprotective and anti-depressive effects of dichloromethane (DCM) fractions of Morus macroura leaves (L) and stem branches (S) on post-myocardial infarction (MI) depression induced by isoprenaline (ISO) in rats in relation to their metabolites. The study was propped with a UPLC-ESI-MS/MS profiling and chromatographic isolation of the secondary metabolites. Column chromatography revealed the isolation of lupeol palmitate (6) that was isolated for the first time from nature with eight known compounds. In addition, more than forty metabolites belonging, mainly to flavonoids, and anthocyanins groups were identified. The rats were injected with ISO (85 mg kg-1, s.c) in the first two days, followed by the administration of M. macroura DCM-L and DCM-S fractions (200 mg kg-1 p.o) for 19 days. Compared with the ISO exposed rats, the treated rats displayed a reduction in cardiac biomarkers (LDH and CKMB), anxiety, and depressive-like behaviour associated with an increase in the brain defense system (SOD and GSH), neuronal cell energy, GABA, serotonin, and dopamine, confirmed by histopathological investigations. In conclusion, DCM-L and DCM-S fractions' cardioprotective and anti-depressive activities are attributed to their metabolite profile. Therefore, they could serve as a potential agent in amending post-MI depression.

The herbal preparation STW 5 affects serotonergic pathways in the brain and colon as well as stress parameters in experimental irritable bowel syndrome.

BACKGROUND: Exposure to stress has been related to disturbance in 5-hydroxytryptamine (5-HT) signaling in the brain-gut axis and is considered as a major predisposing factor for the development of irritable bowel syndrome (IBS). The present study aimed to investigate the possible involvement of 5-HT and some other stress-related parameters in the effectiveness of STW 5 against stress-induced IBS. METHODS: Rats were subjected to restraint stress (RS) for 1 h/day for 14 consecutive days to induce IBS-like symptoms and were given STW 5 orally at the same time. At the end of the experiment, blood samples were withdrawn, then animals were euthanized and the brain hippocampi, cerebral cortices, as well as colons were isolated for biochemical and histopathological assessments. RESULTS: RS increased the plasma corticotrophin releasing factor (CRF) with concomitant increase in hippocampal and cortical 5-HT levels, as well as mast cell inflammatory mediators, oxidative stress biomarkers, and histopathological inflammatory changes observed in rat colon. It also decreased the colonic content of 5-HT with consequent decrease in fecal pellet output (FPO). Treatment with STW 5 protected against these changes. CONCLUSION: The protective effect of STW 5 against RS-induced IBS is related to its ability to normalize the induced changes in 5-HT in the brain-gut axis and counteract the stress-induced oxidative stress and inflammation.

A comparative study between curcumin and curcumin nanoemulsion on high-fat, high-fructose diet-induced impaired spermatogenesis in rats.

OBJECTIVES: Curcumin is a promising nutraceutical with reported diverse therapeutic properties, but of limited oral bioavailability. The current manuscript investigates the role of encapsulation of curcumin in nanoemulsion form in counteracting the adverse effect of chronic ingestion of a high-fat high-fructose diet (HFHF) by juvenile male rats regarding testicular abnormalities and declined spermatogenesis. METHODS: Curcumin nanoemulsion was administered orally to Wistar rats at a dose of 5 or 10 mg/kg and compared with curcumin powder, followed by a pharmacological and histological assessment. KEY FINDINGS: Results demonstrated that curcumin nanoemulsion was superior to curcumin powder, particularly in enhancing the percentage progressive motility of spermatozoa, normalization of essential and non-essential amino acids in semen, normalization of serum leptin and testosterone levels, as well as normalization of oxidative and nitrosative parameters. It was also proven to reduce testicular DNA fragmentation, while elevating testicular cellular energy. In addition, curcumin nanoemulsion administered at a dose of 10 mg/kg induced the highest level of spermatogenesis, delineated by histological examination of the seminiferous tubules. CONCLUSIONS: It can be concluded that curcumin nanoemulsion administered at a dose of 10 mg/kg successfully ameliorates the adverse effects of a HFHF on spermatogenesis.

Performance, Carcass Yield, Muscle Amino Acid Profile, and Levels of Brain Neurotransmitters in Aged Laying Hens Fed Diets Supplemented with Guanidinoacetic Acid.

Guanidinoacetic acid (GA) is a natural precursor of creatine in the body and is usually used to improve the feed conversion and cellular energy metabolism of broiler chickens. The objective was to elucidate the effect of dietary supplementation of GA on carcass yield, muscle amino acid profile, and concentrations of brain neurotransmitters in laying hens. In total, 128 72-week-old ISA Brown laying hens were assigned to four equal groups (32 birds, eight replicates per group). The control group (T1) was fed a basal diet with no supplements, while the other experimental groups were fed a basal diet supplemented with 0.5 (T2), 1.0 (T3), and 1.5 (T4) g GA kg-1 diet. The T3 and T4 groups showed higher hen-day egg production and carcass yield compared to the control group (p = 0.016 and 0.039, respectively). The serum creatine level increased linearly with the increased level of dietary GA (p = 0.007). Among the essential amino acids of breast muscle, a GA-supplemented diet linearly increased the levels of leucine, isoleucine, phenylalanine, methionine, and threonine in the breast (p = 0.003, 0.047, 0.001, 0.001, and 0.015, respectively) and thigh (p = 0.026, 0.001, 0.020, 0.009, and 0.028, respectively) muscles. GA supplementation linearly reduced the level of brain serotonin compared to the control group (p = 0.010). Furthermore, supplementation of GA in the diet of laying hens linearly increased the level of brain dopamine (p = 0.011), but reduced the level of brain Gamma-aminobutyric acid (p = 0.027). Meanwhile, the concentration of brain nitric oxide did not differ between the experimental groups (p = 0.080). In conclusion, the dietary supplementation of GA may improve the carcass yield and levels of essential amino acids in the breast muscles, as well as the brain neurotransmitters in aged laying hens.

Oxidative Stability, Carcass Traits, and Muscle Fatty Acid and Amino Acid Profiles in Heat-Stressed Broiler Chickens.

The objective was to elucidate the effects of chronic heat stress on carcass traits, muscle oxidative stability, muscle fatty acids and amino acid profiles in broiler chickens. A total of 100-day-old male Ross broiler chicks were divided into two equal groups of five replicates. The control group (TN) was maintained on a thermoneutral condition, while the experimental group (HS) was subjected to 8 h of heat stress (34 °C). The HS group showed lower dressing percentage and breast yield compared with the TN group (p = 0.040 and 0.042, respectively). Meanwhile, heat stress significantly increased the percentage of abdominal fat in broiler chickens (p = 0.001). The HS group showed significantly lower levels of PUFA (linoleic, docosahexaenoic and eicosapentaenoic) in the breast (p = 0.003, 0.002 and 0.001, respectively) and thigh (p = 0.001, 0.009 and 0.003, respectively) muscles than did the TN group. The levels of α-lenolinec acid in the breast and thigh muscles did not differ between both experimental groups (p = 0.818 and 0.060, respectively). With exception of threonine, tyrosine and phenylalanine, the levels of essential AA in the breast muscles were significantly (p ˂ 0.05) reduced in the HS group. The HS group showed significantly higher concentration of malondialdehyde (MDA) in the breast muscles (p = 0.032). Meanwhile, the concentration of MDA in the thigh muscles did not differ between both experimental groups (p = 0.149). Furthermore, the HS group showed significantly lower superoxide dismutase and catalase in heart tissues (p = 0.005 and 0.001, respectively). In conclusion, chronic thermal stress deteriorates carcass yield and the oxidative stability of breast muscles, as well as the levels of PUFA and essential AA in broiler chickens. However, the oxidative stability of thigh muscles was not affected.