The effect mechanism of ergosterol from the nutritional mushroom Leucocalocybe mongolica in breast cancer cells: Protein expression modulation and metabolomic profiling using UHPLC-ESI-Q.

The ergosterol from mushrooms has gained significant ethnopharmacological importance in various cultures, including China, Japan, and Europe. This compound has been found to possess immune-boosting and anti-inflammatory properties, making it useful in the treatment of immune disorders. In this study, we focused on investigating the potential anticancer properties of ergosterol isolated from the edible mushroom Leucocalocybe mongolica in breast cancer cell lines. The ergosterol was purified and identified using advanced analytical techniques such as ESI-MS and NMR. We conducted cell proliferation assays on 4 T1 breast cancer cells to assess the cytotoxic effects of ergosterol. Furthermore, we analyzed the transcription levels of BAX, caspase-7, BCL-2, STAT-3, and PARP proteins using real-time PCR and Western blot analysis. Additionally, we employed non-targeted ultra-high-performance liquid chromatography and high-resolution mass spectrometry (UPLC-MS/MS) to study the potential mechanisms underlying the anticancer effects of ergosterol at the metabolomics level. The results demonstrated a significant reduction in cell viability and the induction of apoptosis upon treatment with ergosterol, especially at higher concentrations (P < 0.05). Moreover, ergosterol affected the expression of cancer-related genes, upregulating pro-apoptotic proteins such as BAX, caspase-7, and PARP, while downregulating the anti-apoptotic proteins BCL-2 and STAT-3 (P < 0.05). Western blot analysis confirmed these findings and provided further evidence of ergosterol's role in inducing apoptosis. Metabolomics analysis revealed substantial changes in pathways related to amino acid, antioxidant, and carbohydrate metabolism. In conclusion, our study demonstrates that ergosterol exhibits anticancer effects by inducing apoptosis and modulating metabolic pathways in breast cancer cells.

In vitro and split-faced placebo-controlled in vivo study on the skin rejuvenating effects of cream loaded with bioactive extract of Indigofera argentea Burm.f.

The bioactive extracts of traditional medicinal plants are rich in polyphenols and help to rejuvenate skin. The study was designed to assess the skin rejuvenating effects of a stable cream enriched with 4% I. argentea (IaMe) extract. The quantity of polyphenols by spectrophotometric methods was TPC, 101.55 ± 0.03 mg GAE/g and total flavonoid content; 77.14 ± 0.13 mg QE/g, while HPLC-PDA revealed gallic acid; 4.91, chlorogenic acid 48.12, p-coumaric acid 0.43, and rutin 14.23 µg/g. The significant results of biological activities were observed as DPPH; 81.81% ± 0.05%, tyrosinase; 72% ± 0.23% compared to ascorbic acid (92.43% ± 0.03%), and kojic acid (78.80% ± 0.19%) respectively. Moreover, the promising sun protection effects Sun protection factor of extract (20.53) and formulation (10.59) were observed. The active cream formulation (w/o emulsion) was developed with liquid paraffin, beeswax, IaMe extract, and ABIL EM 90, which was stable for 90 days as shown by various stability parameters. The rheological results demonstrated the active formulation's non-Newtonian and pseudo-plastic characteristics and nearly spherical globules by SEM. The IaMe loaded cream was further investigated on human trial subjects for skin rejuvenating effects and visualized in 3D skin images. Herein, the results were significant compared to placebo. IaMe formulation causes a substantial drop in skin melanin from -1.70% (2 weeks) to -10.8% (12 weeks). Furthermore, it showed a significant increase in skin moisture and elasticity index from 7.7% to 39.15% and 2%-30%, respectively. According to the findings, Indigofera argentea extract has promising bioactivities and skin rejuvenating properties, rationalizing the traditional use and encouraging its exploitation for effective and economical cosmeceuticals.

Suppression of Root Rot Fungal Diseases in Common Beans (Phaseolus vulgaris L.) through the Application of Biologically Synthesized Silver Nanoparticles.

The biosynthesis of silver nanoparticles (AgNPs) using plant extracts has become a safe replacement for conventional chemical synthesis methods to fight plant pathogens. In this study, the antifungal activity of biosynthesized AgNPs was evaluated both in vitro and under greenhouse conditions against root rot fungi of common beans (Phaseolus vulgaris L.), including Macrophomina phaseolina, Pythium graminicola, Rhizoctonia solani, and Sclerotium rolfsii. Among the eleven biosynthesized AgNPs, those synthesized using Alhagi graecorum plant extract displayed the highest efficacy in suppressing those fungi. The findings showed that using AgNPs made with A. graecorum at a concentration of 100 µg/mL greatly slowed down the growth of mycelium for R. solani, P. graminicola, S. rolfsii, and M. phaseolina by 92.60%, 94.44%, 75.93%, and 79.63%, respectively. Additionally, the minimum inhibitory concentration (75 µg/mL) of AgNPs synthesized by A. graecorum was very effective against all of these fungi, lowering the pre-emergence damping-off, post-emergence damping-off, and disease percent and severity in vitro and greenhouse conditions. Additionally, the treatment with AgNPs led to increased root length, shoot length, fresh weight, dry weight, and vigor index of bean seedlings compared to the control group. The synthesis of nanoparticles using A. graecorum was confirmed using various physicochemical techniques, including UV spectroscopy, Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) analysis. Collectively, the findings of this study highlight the potential of AgNPs as an effective and environmentally sustainable approach for controlling root rot fungi in beans.

Fumaria indica (Hausskn.) Pugsley Hydromethanolic Extract: Bioactive Compounds Identification, Hypotensive Mechanism, and Cardioprotective Potential Exploration.

Fumaria indica (Hausskn.) Pugsley (FIP), a member of the Papaveraceae family, has a documented history of use in traditional medicine to treat cardiovascular ailments, particularly hypertension, and has shown substantial therapeutic efficacy among native cultures worldwide. However, the identification of bioactive compounds and the mechanism of hypotensive effect with the cardioprotective potential investigations are yet to be determined. The study aimed to identify bioactive compounds, explore the hypotensive mechanism and cardioprotective potential, and assess the safety of Fumaria indica (Hausskn.) Pugsley hydromethanolic extract (Fip.Cr). LC ESI-MS/MS analysis was performed to identify the bioactive compounds. In vitro experiments were conducted on isolated rat aorta and atria, and an in vivo invasive BP measurement model was used. Acute and subacute toxicities were assessed for 14 and 28 days, respectively. Isoproterenol (ISO) was used to develop the rats' myocardial infarction damage model. The mRNA levels of NLRP3 inflammasome and the abundance level of Firmicutes and Lactobacillus were measured by qRT-PCR. The hypotensive effect of FIP bioactive compounds was also investigated using in silico methods. Fip. Cr LC ESI-MS/MS analysis discovered 33 bioactive compounds, including alkaloids and flavonoids. In isolated rat aorta, Fip.Cr reversed contractions induced by K+ (80 mM), demonstrating a calcium entry-blocking function, and had a vasorelaxant impact on phenylephrine (PE) (1 µM)-induced contractions unaffected by L-NAME, ruling out endothelial NO participation. Fip.Cr caused negative chronotropic and inotropic effects in isolated rat atria unaffected by atropine pretreatment, eliminating cardiac muscarinic receptor involvement. Safety evaluation showed no major adverse effects. In vivo, invasive BP measurement demonstrated a hypotensive effect comparable to verapamil. Fip.Cr protected the rats from ISO-induced MI interventions significantly in biometrical and cardiac serum biochemical indicators and histological examinations by reducing inflammation via inhibiting NLRP3 inflammasome and elevating Firmicutes and Lactobacillus levels. The network pharmacology study revealed that the FIP hypotensive mechanism might involve MMP9, JAK2, HMOX1, NOS2, NOS3, TEK, SERPINE1, CCL2, and VEGFA. The molecular docking study revealed that FIP bioactive compounds docked better with CAC1C_ HUMAN than verapamil. These findings demonstrated that Fip.Cr's hypotensive mechanism may include calcium channel blocker activity. Fip.Cr ameliorated ISO-induced myocardial infarction in rats by attenuating inflammation, which might be via inhibiting NLRP3 inflammasome and may prove beneficial for treating MI.

Efficacy of Dietary Supplementation with Zinc-Chromium Mixture, Organic Selenium, or Their Combinations on Growth Performance, Carcass Traits, and Blood Profiles of Broilers under Heat Stress Conditions.

To determine the effects of organic selenium (0.0-0.6 mg and 0.9 mg Se/Kg diet) and Zn-Cr mixture (100 mg Zn/Kg diet plus 1.5 mg Cr/Kg diet) on broiler chicken performance, carcass traits, blood hematology, and biochemistry under heat stress conditions, this study was conducted. Under temperatures between 30.21 to 31.82 °C, 240 broiler chickens (Ross-308), which were 7-day-old, were randomly assigned to one of six treatments: T1 (control), T2 (100 mg Zn per kg of diet and 1.5 mg Cr per kg of diet), T3 (0.6 mg Se per kg of diet), T4 (0.9 mg Se per kg of diet), T5 (100 mg Zn, 1.5 mg Cr and (LSe), and T6 (100 mg Zn, 1.5 mg Cr and (HSe)). At 35 days old, the chicks fed a diet containing Zn-Cr with low or high organic selenium (organic-Se) outweighed the control group in terms of live body weight, weight gain, and feed conversion ratio (p < 0.05). In comparison to the control treatment, birds fed diets supplemented with Zn-Cr or organic-Se (LSe, HSe) significantly increased their serum levels of total protein and total antioxidant capacity. However, these additives resulted in a decrease (p < 0.01) in their serum levels of triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, creatinine, and uric acid. Together, it was found that trace elements (Zn-Cr and organic-Se) may greatly lessen the impacts of heat stress on broilers by promoting growth performance and boosting metabolic processes.

Antiplatelet, cytotoxic activities and characterization of green-synthesized zinc oxide nanoparticles using aqueous extract of Nephrolepis exaltata.

The goal of the current study was to synthesize zinc oxide nanoparticles (ZnO-NPs) using ZnCl2.2H2O salt precursor and an aqueous extract of Nephrolepis exaltata (N. exaltata), which act as a capping and reducing agent. N. exaltata plant extract-mediated ZnO-NPs were further characterized by various techniques, such as X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), UV-visible (UV-Vis), and energy-dispersive X-ray (EDX) analysis. The nanoscale crystalline phase of ZnO-NPs was analyzed by the XRD patterns. The FT-IR analysis revealed different functional groups of biomolecules involved in the reduction and stabilization of the ZnO-NPs. The light absorption and optical properties of ZnO-NPs were examined by UV-Vis spectroscopy at a wavelength of 380 nm. The spherical shape morphology of ZnO-NPs with mean particle size ranges between 60 and 80 nm was confirmed by SEM images. While the EDX analysis was used to identify the elemental composition of ZnO-NPs. Furthermore, the synthesized ZnO-NPs demonstrate potential antiplatelet activity by inhibiting the platelet aggregation induced by platelet activation factor (PAF) and arachidonic acid (AA). The results showed that synthesized ZnO-NPs were more effective in inhibiting platelet aggregation induced by AA with IC50 (56% and 10 µg/mL) and PAF (63% and 10 µg/mL), respectively. However, the biocompatibility of ZnO-NPs was assessed in human lung cancer cell line (A549) under in vitro conditions. The cytotoxicity of synthesized nanoparticles revealed that cell viability decreased and the IC50 was found to be 46.7% at a concentration of 75 µg/mL. The present work concluded the green synthesis of ZnO-NPs that was achieved by N. exaltata plant extract and showed good antiplatelet and cytotoxic activity, which demonstrates the lack of harmful effects making them more effective for use in pharmaceutical and medical fields to treat thrombotic disorders.

Supplementation of Morin Restores the Altered Bone Histomorphometry in Hyperglycemic Rodents via Regulation of Insulin/IGF-1 Signaling.

Pathological mechanisms underlining diabetic bone defects include oxidative damage and insulin/IGF-1 imbalance. Morin is a bioflavonoid with antioxidant and anti-diabetic effects. This study evaluates morin's protective effects against altered bone histomorphometry in diabetic rats through assessing insulin/IGF-1 pathway as a potential mechanism. Diabetic animals were administered two morin doses (15 and 30 mg/kg) for 5 weeks. Different serum hepatic and renal functions tests were assessed. Bone density and histomorphometry in cortical and trabecular tissues were evaluated histologically. The expressions of insulin, c-peptide and IGF-1 were estimated. In addition, the enzymatic activities of the major antioxidant enzymes were determined. Diabetic-associated alterations in serum glucose, aminotransferases, urea and creatinine were attenuated by morin. Diabetic bone cortical and trabecular histomorphometry were impaired with increased fibrosis, osteoclastic functions, osteoid formation and reduced mineralization, which was reversed by morin; particularly the 30 mg/kg dose. Insulin/IGF-1 levels were diminished in diabetic animals, while morin treatment enhanced their levels significantly. Diabetes also triggered systemic oxidative stress noticeably. The higher dose (30 mg/kg) of morin corrected the endogenous antioxidant enzymatic activities in diabetic rats. Findings indicate the potential value of morin supplementation against hyperglycemia-induced skeletal impairments. Activation of insulin/IGF-1 signaling could be the underlining mechanism behind these effects.

Flavonoids from Marine-Derived Actinobacteria as Anticancer Drugs.

Flavonoids represent a large diverse group of natural products that are used as a traditional medicine against various infectious diseases. They possess many biological activities including antimicrobial, antioxidant, anti-inflammatory, anti-cancer and anti-diabetic activities. Commercially, flavonoids are mainly obtained from plants, however, several challenges are faced during their extraction. Microorganisms have been known as natural sources of a wide range of bioactive compounds including flavonoids. Actinobacteria are the most prolific group of microorganisms for the production of bioactive secondary metabolites, thus facilitating the production of flavonoids. The screening programs for bioactive compounds revealed the potential application of actinobacteria to produce flavonoids with interesting biological activities, especially anticancer activities. Since marine actinobacteria are recognized as a potential source of novel anticancer agents, they are highly expected to be potential producers of anticancer flavonoids with unusual structures and properties. In this review, we highlight the production of flavonoids by actinobacteria through classical fermentation, engineering of plant biosynthetic genes in a recombinant actinobacterium and the de novo biosynthesis approach. Through these approaches, we can control and improve the production of interesting flavonoids or their derivatives for the treatment of cancer.

Efficacy of Dietary Supplementation with Capsicum Annum L on Performance, Hematology, Blood Biochemistry and Hepatic Antioxidant Status of Growing Rabbits.

Animals fed with a high amount of a wide range of antioxidants in their diet are significantly protected against oxidative stress. Powerful antioxidant substances such as vitamin E, vitamin C, and carotenoids are present naturally in red-hot pepper (RHP). This study hypothesized that using RHP may provide protection against oxidative stress and enhance animal physiological responses. Thus, this study aimed to investigate the effect of feeding New Zealand white rabbits with RHP-supplemented diets on their physiological and biochemical responses. New Zealand White rabbits (age = 6 weeks, n = 48) were split equally into three groups (n = 16 in each group). One group was fed a basal diet only (control group), with the other two groups fed a basal diet along with 1 and 2% RHP. Mass spectrometric analysis for the RHP methanolic extract showed some phenolic compounds, such as p-coumaric, sinapinic acids, vanillic, and luteolin, as well as catechin and its isomers. Hepatic antioxidant enzymes (SOD, GSH, GSH-Px, and CAT) were significantly elevated (p < 0.05) by feeding rabbits diets supplemented with 1 or 2% RHP. The addition of RHP significantly enhanced immune-responses; phagocytic activity, chemotaxis, TIg, IgG, IgM, and IgA increased when growing rabbits were fed RHP compared with the control group. In conclusion, dietary supplementation of 1 or 2% RHP may play a role as an enhancer of growth and immune response in growing rabbits.

Baicalein Neutralizes Hypercholesterolemia-Induced Aggravation of Oxidative Injury in Rats.

Hypercholesterolemia is a major risk factor for several cardiovascular and metabolic diseases as it triggers oxidative and pro-inflammatory cascades. Baicalein (BL) is a natural flavone with multiple therapeutic properties. The present study aimed to evaluate the potential protective effect of BL supplementation in hypercholesterolaemic rats. Rats were fed a high-cholesterol diet (HCD) for six weeks and then orally administered BL at two doses (25 and 50 mg/kg body weight/day) for four weeks. Serum lipids, liver enzymes, cardiac enzymes, renal markers, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), interleukin-10 (IL-10), caspase-3, nitric oxide (NO) and prostaglandin-2 (PGE-2) were measured. In renal, hepatic, and cardiac tissues, thiobarbituric acid-reactive (TBARS) substance, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured. The altered levels of lipoproteins, aminotransferases, creatine kinases, and urea in hypercholesterolemic animals were significantly corrected by BL. Inflammatory and apoptotic biomarkers were also markedly attenuated in the HCD group following BL treatment. Hypercholesterolemia considerably induced the lipid peroxidation product, TBARS, and oxidative radicals in cardiac, hepatic, and renal tissues, which were attenuated by BL treatment, particularly, at the 50 mg/kg/day dose. BL enhanced the activities of superoxide dismutase, catalase, and glutathione peroxidase that were suppressed by HCD. Histological alterations induced by cholesterol overload in cardiac, hepatic, and renal tissues were ameliorated by BL supplementation. Our results show that the BL treatments (25 and 50 mg/kg/day) to HCD fed rats improved all the altered parameters. These results demonstrate that BL treatment improves cardiac, renal and hepatic dysfunctions in hypercholesterolaemic rats by activation of cellular antioxidant enzymes and/or suppression of inflammatory cytokines.

Protective Role of Loranthus regularis against Liver Dysfunction, Inflammation, and Oxidative Stress in Streptozotocin Diabetic Rat Model.

Earlier studies revealed the potential therapeutic values of Loranthus regularis (L. regularis). This study evaluated Loranthus regularis (L. regularis) extract systemic antidiabetic effects and benefits against diabetic hepatocellular injuries through antioxidant and anti-inflammatory pathways using the streptozotocin (STZ) model in Wistar albino rats. After diabetes induction, animals were orally treated with L. regularis extract for 4 weeks. Serum levels of glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were estimated. Furthermore, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), caspase-3, nitric oxide (NO), and prostaglandin E-2 (PGE-2) were estimated in serum. In liver, thiobarbituric acid reactive substances (TBARSs) and reduced glutathione (GSH) as well as the proinflammatory cytokines and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reeducates (GR), and glutathione-S-transferase (GST) were assayed. Finally, the degree of hepatic tissue damage was evaluated histologically. Treatment of the diabetic rats with L. regularis extract markedly reduced the elevated serum levels of glucose, ALT, AST, TC, TG, LDL, TNF-α, IL-1ß, IL-6, caspase-3, NO, and PGE-2. L. regularis extract also improved serum levels of insulin and HDL. The elevated TBARS, TNF-α, IL-1ß, and IL-6 levels in hepatic tissue of diabetic animals were reduced by L. regularis. Moreover, L. regularis extract significantly restored the diminished hepatic GSH level and enzymatic activities of SOD, CAT, GPx, GR, and GST in diabetic animals. The biochemical protective effects of L. regularis were associated with improved histological hepatocellular integrity and architecture. Taken together, L. regularis has therapeutic effects against diabetic-induced hepatic complications. The restored liver functions and cellular damage might be mediated through free radicals scavenging and proinflammatory cytokine inhibition.

Differential responses of two cyanobacterial species to R-metalaxyl toxicity: Growth, photosynthesis and antioxidant analyses.

Metalaxyl is a broad-spectrum chiral fungicide that used for the protection of plants, however extensive use of metalaxyl resulted in serious environmental problems. Thus, a study on the detoxification mechanism in algae/cyanobacteria and their ability for phycoremediation is highly recommended. Here, we investigated the physiological and biochemical responses of two cyanobacterial species; Anabaena laxa and Nostoc muscorum to R-metalaxyl toxicity as well as their ability as phycoremediators. Two different levels of R-metalaxyl, at mild (10 mg/L) and high dose (25 mg/L), were applied for one-week. We found that A. laxa absorbed and accumulated more intracellular R-metalaxyl compared to N. muscorum. R-metalaxyl, which triggered a dose-based reduction in cell growth, photosynthetic pigment content, and photosynthetic key enzymes' activities i.e., phosphoenolpyruvate carboxylase (PEPC) and ribulose‒1,5‒bisphosphate carboxylase/oxygenase (RuBisCo). These decreases were significantly less pronounced in A. laxa. On the other hand, R-metalaxyl significantly induced oxidative damage markers, e.g., H2O2 levels, lipid peroxidation (MDA), protein oxidation and NADPH oxidase activity. However, these increases were also lower in A. laxa compared to N. muscorum. To alleviate R-metalaxyl toxicity, A. laxa induced the polyphenols, flavonoids, tocopherols and glutathione (GSH) levels as well as peroxidase (POX), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-s-transferase (GST) enzyme activities. On the contrary, the significant induction of antioxidants in N. muscorum was restricted to ascorbate, catalase (CAT) and ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR) enzyme activities. Although A. laxa accumulated more R-metalaxyl, it experienced less stress due to subsequent induction of antioxidants. Therefore, A. laxa may be a promising R-metalaxyl phycoremediator. Our results provided basic data for understanding the ecotoxicology of R-metalaxyl contamination in aquatic habitats and the toxicity indices among cyanobacteria.

The effects of dietary tomato powder (Solanum lycopersicum L.) supplementation on the haematological, immunological, serum biochemical and antioxidant parameters of growing rabbits.

Using nutritional antioxidants in livestock systems is considered the key in improving animal production. The current study assumes that dietary tomato powder (TP) supplementation positively affects haemato-immunological, biochemical, and antioxidant parameters for New Zealand rabbits. A total of 30 rabbits (45 days old) were assigned to three groups, including a diet with no additives (control), and two dietary treatments with the providing of 1% or 2% TP. Mass spectrometric study for TP methanolic extract showed some phenolic compounds. Consumption of TP supplemented diets significantly (p < 0.001) affected body weight gain and feed efficiency. Red blood cells and white blood cells count exhibited a significant increase (p < 0.001) in both TP groups compared with the control. In addition to, feeding rabbits on TP enhanced cell-mediated and humoral immune responses through a significant increase in phagocytosis, chemotaxis, and levels of immunoglobulins (TIg, IgG, IgM and IgA). Supplementation of TP significantly (p < 0.01) reduced lipid profile induces except high-density lipoprotein cholesterol values. A remarkable significant (p < 0.001) effect on serum and hepatic oxidative stress responses were observed with TP addition. Ultimately, TP supplementation could play a potential role as a growth and health enhancer for fattening rabbits.

Syzygium Aromaticum Alleviates Cerium Chloride-Induced Neurotoxic Effect In The Adult Mice.

Previous studies have brought to light the toxic effect of cerium chloride (CeCl3) but very little is known about the oxidative brain injury caused by this metal. Medical plants have a well-recognized role in the management of damage caused by pollutants such as CeCl3. Syzygium aromaticum, a potent natural source of bioactive compounds and rich in secondary metabolites, has a broad range of biological functions. The aim of this study is to investigate the capacity of Syzygium aromaticum ethanol extract (ESA) to improve the adverse effects of CeCl3 in the brain tissue. Adult mice were exposed to CeCl3 (20 mg/kg body weight [BW]), with or without ESA, for 60 days. We investigate mice's behavior, damages of cholinergic system and oxidative stress parameters in mice brain. In the present study, in vitro test confirmed that ESA has antioxidant capacity attributed to the presence of flavonoids, polyphenols, and tannins contents. In vivo study showed that CeCl3 caused brain injuries manifested in memory impairment, increase in acetylcholinesterase activity, oxidative stress biomarkers (lipid, proteins, enzymatic and non-enzymatic antioxidant systems), and histopathological alteration in brain tissue. Addition of ESA repaired memory impairment, decreased acetylcholinesterase activity, restored oxidative state, and prevented histopathological alteration. In conclusion, the experimental results showed the protective effects of ethanol extract of Syzygium aromaticum against cerium-induced brain damage.

Neurobehavioral changes in mice offspring exposed to green tea during fetal and early postnatal development.

BACKGROUND: Green tea extract (GTE) has various health promoting effects on animals and humans. However, the effects of perinatal exposure to GTE on the behavioral aspects of offspring have not been elucidated thus far. GTE was provided for pregnant female mice at concentrations of either 20 or 50 g/L, beginning the day of conception until the third week after delivery, postnatal day 22 (PD 22). Mice pups were subjected to behavioral testing to assess sensory motor reflexes, locomotion, anxiety, and learning on various postnatal days. RESULTS: Perinatal exposure to GTE resulted in a significant reduction in body weight, as well as earlier body hair appearance and opening of the eyes. Sensory motor reflexes exhibited faster responses and significant stimulatory effects in pups exposed to GTE. During the adolescent period, male and female offspring exhibited increased locomotor activity (on PD 22), reduced anxiety and fear (on PD 25), and enhanced memory and learning abilities (on PD 30), all in both GTE treated groups. All blood counts (RBCs, WBCs, Hb, and platelets), and glucose, cholesterol, triglyceride, and low density lipoprotein concentrations were significantly lower in the GTE-treated pups; however, there was no effect on high density lipoprotein levels. CONCLUSION: Our data provide evidence that the high dose of GTE (50 g/L) had higher anxiolytic properties and positive effects on locomotor activities and sensory motor reflexes, as well as learning and memory of the offspring than the low dose of GTE (20 g/L).

Treatment of diabetic mice with undenatured whey protein accelerates the wound healing process by enhancing the expression of MIP-1α, MIP-2, KC, CX3CL1 and TGF-ß in wounded tissue.

BACKGROUND: Continuous diabetes-associated complications are a major source of immune system exhaustion and an increased incidence of infection. Diabetes can cause poor circulation in the feet, increasing the likelihood of ulcers forming when the skin is damaged and slowing the healing of the ulcers. Whey proteins (WPs) enhance immunity during childhood and have a protective effect on some immune disorders. Therefore, in this study, we investigated the effects of camel WP on the healing and closure of diabetic wounds in a streptozotocin (STZ)-induced type I diabetic mouse model. RESULTS: Diabetic mice exhibited delayed wound closure characterized by a significant decrease in an anti-inflammatory cytokine (namely, IL-10) and a prolonged elevation of the levels of inflammatory cytokines (TNF-α, IL-1ß and IL-6) in wound tissue. Moreover, aberrant expression of chemokines that regulate wound healing (MIP-1α, MIP-2, KC and CX3CL1) and growth factors (TGF-ß) were observed in the wound tissue of diabetic mice compared with control nondiabetic mice. Interestingly, compared with untreated diabetic mice, supplementation with WP significantly accelerated the closure of diabetic wounds by limiting inflammatory stimuli via the restoration of normal IL-10, TNF-α, IL-1ß and IL-6 levels. Most importantly, the supplementation of diabetic mice with WP significantly modulated the expression of MIP-1α, MIP-2, KC, CX3CL1 and TGF-ß in wound tissue compared with untreated diabetic mice. CONCLUSION: Our data demonstrate the benefits of WP supplementation for improving the healing and closure of diabetic wounds and restoring the immune response in diabetic mice.

Modulation of immune cell proliferation and chemotaxis towards CC chemokine ligand (CCL)-21 and CXC chemokine ligand (CXCL)-12 in undenatured whey protein-treated mice.

Whey protein concentrates (WPCs) enhance innate mucosal immunity during early life and have a protective role in some immune disorders. To further elucidate the potential benefits of this protein, the present study investigated the effect of dietary supplementation with WPCs on blood parameters, plasma cytokine profiles, and immune cell proliferation and chemotaxis. A total of 45 male mice were equally distributed into three experimental groups and treated daily for 21 days as follows: group I was a control group that was orally supplemented with distilled water, group II was orally supplemented with undenatured WP (100 mg/kg body weight), and group III was orally supplemented with bovine serum albumin (100 mg/kg body weight). We found that the plasma cytokine levels of interleukin (IL)-1α, IL-1ß, IL-10 and tumor necrosis factor-α and the levels of reactive oxygen species, cholesterol, triglycerides and the lipid profile were significantly decreased in the WP-treated group compared to the control group. In contrast, the levels of IL-2, IL-4, IL-7, IL-8 and glutathione were significantly elevated, and consequently, the ability of peripheral blood mononuclear cells to proliferate in response to stimulation with different antigens was significantly increased in the WP-treated group. Moreover, the in vitro chemotaxis of B, T and bone-marrow-derived dendritic cells toward CC chemokine ligand-21 and CXC chemokine ligand-12 was significantly increased, by twofold, in WP-treated mice compared to the control group. Taken together, our data reveal the benefits of WP supplementation in enhancing immune cell proliferation and migration to the secondary lymphoid organs.

Vitamin C supplementation reconstitutes polyfunctional T cells in streptozotocin-induced diabetic rats.

BACKGROUND: Studies have demonstrated that vitamin C supplementation enhances the immune system, prevents DNA damage, and decreases the risk of a wide range of diseases. Other study reported that leukocyte vitamin C level was low in diabetic individuals compared with nondiabetic controls. AIM OF THE WORK: To study the effect of vitamin C on oxidative stress, blood lipid profile, and T-cell responsiveness during streptozotocin (STZ)-induced type I diabetes mellitus. METHODS: Thirty male Sprague-Dawley rats were randomly split into three groups. The first served as a control group (n = 10) in which rats were injected with the vehicle alone. The second (n = 10) and the third groups (n = 10) were rendered diabetic by intraperitoneal (i.p.) injection of single doses of STZ (60 mg/kg body weight). The third group was supplemented with vitamin C (100 mg/kg body weight) for 2 months. RESULTS: T lymphocytes from the diabetic rats were found to be in a stunned state, with a decreased surface expression of the CD28 costimulatory molecule, low levels of phosphorylated AKT, altered actin polymerization, diminished proliferation and cytokine production, and, eventually, a marked decrease in abundance in the periphery. Vitamin C was found to significantly decrease the elevated levels of blood hydroperoxide, glucose, cholesterol, triglycerides and low-density lipoprotein (LDL) in diabetic rats. Furthermore, it was found to restore CD28 expression, AKT phosphorylation, actin polymerization, and polyfunctional T cells (IFN-γ- and IL-2-producing cells that exhibit a high proliferation capacity). CONCLUSION: Vitamin C treatment restores and reconstitutes polyfunctional, long-lived T cells in diabetic rats.

Thymoquinone decreases F-actin polymerization and the proliferation of human multiple myeloma cells by suppressing STAT3 phosphorylation and Bcl2/Bcl-XL expression.

BACKGROUND: Thymoquinone (TQ), the major active component of the medicinal herb Nigella sativa Linn., has been described as a chemopreventive and chemotherapeutic compound. METHODS: In this study, we investigated the effect of TQ on survival, actin cytoskeletal reorganization, proliferation and signal transduction in multiple myeloma (MM) cells. RESULTS: We found that TQ induces growth arrest in both MDN and XG2 cells in a dose- and time-dependent manner. TQ also inhibited CXC ligand-12 (CXCL-12)-mediated actin polymerization and cellular proliferation, as shown by flow cytometry. The signal transducer and activator of transcription (STAT) and B-cell lymphoma-2 (Bcl-2) signaling pathways may play important roles in the malignant transformation of a number of human malignancies. The constitutive activation of the STAT3 and Bcl-2 pathways is frequently observed in several cancer cell lines, including MM cells. Using flow cytometry, we found that TQ markedly decreased STAT3 phosphorylation and Bcl-2 and Bcl-XL expression without modulating STAT5 phosphorylation in MM cells. Using western blotting, we confirmed the inhibitory effect of TQ on STAT3 phosphorylation and Bcl-2 and Bcl-XL expression. CONCLUSIONS: Taken together, our data suggests that TQ could potentially be applied toward the treatment of MM and other malignancies.