Nanoliposome-loaded phenolics from Salvia leriifolia Benth and its anticancer effects against induced colorectal cancer in mice.

Colon cancer is one of the leading causes of death among various types of cancer. Despite the significant progress made in cancer treatment, chemotherapy resistance and various side effects are still prevalent. The objective of this study is to assess the therapeutic potential of phenolic-rich fraction encapsulated nanoliposome (PRF-NLs) of Salvia leriifolia Benth in the treatment of colon cancer in mice. Initially, the phenolic-rich fraction (PRF) was extracted and then encapsulated into nanoliposomes. The physicochemical properties of the nanoliposomes were evaluated using dynamic light scattering, zeta potential, and field emission scanning electron microscopy. Subsequently, 24 mice with HT-29 colon cancer cells were divided into three groups, and the anticancer effects of PRF-NLs were measured. The results showed that the ethyl acetate fraction of S. leriifolia was the highest PRF containing 14.27 ± 2.39 mg (gallic acid) GA/g DW (dry weight), and the PRF successfully loaded into the nanoliposome structure resulted in the synthesis of nanoliposomes with a nanometer size and spherical shape and homogenous dispersion. Some of the abundant bioactive phenolic compounds in the nanoliposome-loaded PRF are salicylic acid and naringin. The average daily weight gain and food intake, and changes in the expression of caspase 3, Bax (Bcl-2 associated X-protein), and Bcl2 (B-cell lymphoma 2), inducible nitric oxide synthase genes, were observed in the mice group induced colorectal cancer cells. At a dose of 100 mg TPC (total phenolic content)/kg BW/day, the nonencapsulated PRF dietary addition improved these parameters; however, the potential shown by nanoliposome-encapsulated PRF than the nonencapsulated PRF in enhancing health parameters in mice was higher. The developed intestinal absorption and bioavailability of nanoliposome-encapsulated PRF contribute to its increased health-promoting activity. Thereby, the synthesized nanoliposome may be a potential natural anticancer drug to prevent colorectal cancer.

Biosorption and Bioprotective Potential of Levilactobacillus brevis in Mice Challenged by Lead-Induced Oxidative Stress.

Lead (Pb) poisoning is a widespread issue in both developed and developing countries that poses a significant public health challenge. Our study aimed to explore the impact of Levilactobacillus brevis strains on inflammatory and antioxidant gene expression in the liver and brain of mice exposed to oxidative stress caused by Pb. We began by evaluating Pb absorption by Levilactobacillus brevis strains (ARKA-CH-1 (A1) and ARKA-CH-6 (A6)) using the inductively coupled plasma mass spectrometry (ICP-MS) in vitro to identify the most effective strain. We then divided four groups of BALB/c mice into control and experimental groups and treated them for 30 days. The control group received a normal diet, while the experimental groups consumed lead-containing water (0.6 g/L) with or without Levilactobacillus brevis strains. Following the experiments, we collected blood samples to test liver markers, antioxidant enzymes, and immunoglobulins. We also used real-time PCR to examine the expression of superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) genes. The results showed that the A1 strain was the most effective in absorbing Pb. The Pb exposure led to an increase in liver enzyme values and a decrease in antioxidant enzyme activity and immunoglobulin factors. However, the combination of A1 and A6 strains had a greater effect in reducing inflammatory enzymes and increasing antioxidant enzymes. Furthermore, we observed a significant increase in iNOS gene expression and a notable decrease in SOD gene expression with Pb consumption. However, the combination of A1 and A6 strains had a synergistic effect in reducing iNOS and increasing SOD gene expression. In conclusion, Levilactobacillus brevis A1 strain alone or in combination with the A6 strain could be a promising strategy to mitigate the oxidative stress symptoms in mice challenged by lead-induced toxicity.

The anti-spermatogenic activity of nanoliposomes loaded with Heracleum persicum phenolic compounds in Balb/C mice.

There are various types of bioactivities that have been reported for Heracleum persicum species, such as antioxidant, anti-inflammatory, and cytotoxicity properties. In the current study, the bio-accessibility of H. persicum bioactive compounds was improved by purifying its phenolic-enriched fractions (PEF) and encapsulating them into nanoliposomes to analyze its cytotoxic impacts on mice testicular tissue and their fertility status. Nano liposomal H. persicum PEF (NL-HPEF) was prepared by ultrasound-based encapsulation of HPEF and L-agranular lecithin mixture. The size, morphology, and stability of NL-HPEF were characterized by dynamic light scattering, field emission scanning electron microscopy, and zeta potential analysis. The 18 white male Balb/c mice (20-25 g) at 3 treatment groups were provided to study the NL-HPPF cytotoxicity by measuring the mice liver enzyme including aspartate aminotransferase (AST), ALP and alanine aminotransferase (ALT), testis lipid peroxidation, and testicular tissue destruction levels. Moreover, the mice's fertility was evaluated by studying the Adam3, Prm1, Spata19, and Tnp2 gene expression in the testicular tissues. The obtained results manifested that the synthesized NL-HPEF was stable (193.7 nm) and exhibited a notable cytotoxic impact on the mice's liver (ALT and AST enhancement levels) and testicular tissues. Moreover, their increasing treatment doses impaired the male mice's fertility by decreasing the sperm count, viability, and motility. In addition, fertility suppression was verified by decreasing serum testosterone and downregulating the Adam3, Prm1, Spata19, and Tnp2 gene expression in their testicular tissues. The male mice's fertility was significantly (p < 0.05) suppressed by increasing treatment doses of NL-HPEF. Hence, the NL-HPEF could be considered a promising alternative to replace the male chemical contraceptives drugs.

Enhancing Healthcare Outcomes and Modulating Apoptosis- and Antioxidant-Related Genes through the Nano-Phytosomal Delivery of Phenolics Extracted from Allium ampeloprasum.

The application of nano drug delivery systems, particularly those utilizing natural bioactive compounds with anticancer properties, has gained significant attention. In this study, a novel nano-phytosome-loaded phenolic rich fraction (PRF) derived from Allium ampeloprasum L. was developed. The antitumor activity of the formulation was evaluated in BALB/c mice with TUBO colon carcinoma. The PRF-loaded nano-phytosome (PRF-NPs) exhibited a sphere-shaped structure (226 nm) and contained a diverse range of phenolic compounds. Animal trials conducted on TUBO tumor-bearing mice demonstrated that treatment with PRF-NPs at a dosage of 50 mg TPC/Kg/BW resulted in significant improvements in body weight and food intake, while reducing liver enzymes and lipid peroxidation. The expression of apoptosis-related genes, such as Bax and caspase-3, was upregulated, whereas Bcl2 was significantly downregulated (p < 0.05). Furthermore, the expression of GPx and SOD genes in the liver was notably increased compared to the control group. The findings suggest that the phytosomal encapsulation of the phenolic rich fraction derived from Allium ampeloprasum L. can enhance the bioavailability of natural phytochemicals and improve their antitumor properties. The development of PRF-NPs as a nano drug delivery system holds promise for effective breast cancer treatment.

Microcapsules loaded with date seed extract and its inhibitory potential to modulate the toxic effects of mycotoxins in mice received mold-contaminated diet.

Mycotoxins are the secondary fungal metabolites generally produced by wide range of fungi including aflatoxins (AF), ochratoxin A (OTA), fumonisins (FB), zearalenone (ZEN), and deoxynivalenol (DON). Nowadays, they are main concern to food and agricultural commodities due to undesirable health and socio-economic effect. This investigation was designed to synthesized microcapsules loaded the bioactive compounds of date seed and evaluated its inhibitory activities in mice received mold-contaminated diet. The finding revealed that the developed microcapsule is homogenous and mostly spherical with size of 2.58 µm with acceptable PDI of 0.21. The main phytochemical has been confirmed by HPLC analysis were xylose, fructose, mannose, glucose, and galactose with the respective values of 41.95%, 2.24%, 5.27%, and 0.169%. The in vivo analyses manifested that the mice received date seed microcapsules significantly (p < 0.05) improved the average daily weight gain, feed intake, liver enzymes (ALT, ALP, and AST), and lipid peroxidation values compare to mice group received mycotoxin-contaminated diet. Furthermore, encapsulation date seed bioactive compounds notably up-regulated the expression of GPx, SOD, IFN-γ, and IL-2 genes while down-regulated the iNOS gene. Consequently, the novel microcapsules loaded date seed is suggested to be considered as a promising mycotoxin inhibitor.

Encapsulation of Polygonum bistorta root phenolic compounds as a novel phytobiotic and its protective effects in the mouse model of enteropathogenic Escherichia coli infection.

BACKGROUND: Microencapsulation technology is the fundamental delivery system for encapsulating the natural bioactive compounds especially phenolic in order to developing bioavailability, stability and controlling release. This study was conducted to determine the antibacterial and health-promoting potential of the phenolic rich extract (PRE)-loaded microcapsules obtained from Polygonum bistorta root as a dietary phytobiotic in mice challenged by enteropathogenic Escherichia coli (E. coli). METHOD: The PRE was obtained from Polygonum bistorta root using fractionation by different polarity solvents and the highest PRE was encapsulated by the combination of modified starch, maltodextrin, and whey protein concentrate as wall materials using a spray dryer. Then, the physicochemical characterization (particle size, zeta potential, Morphology and polydispersity index) of microcapsules have been assessed. For the invivo study, 30 mice at five treatment were designed and antibacterial properties were analyzed. Furthermore, relative fold changes in the ileum population of E. coli was investigated using Real time PCR. RESULTS: The encapsulation of PRE resulted in the production of phenolic enriched extract-loaded microcapsules (PRE-LM) with a mean diameter of 330 nm and relatively high entrapment efficiency (87.2% w/v). The dietary supplementation of PRE-LM improved weight gain, liver enzymes, gene expression, morphometric characteristics of the ileum and decreased the population of E. coli present in the ileum significantly (p < 0.05). CONCLUSION: Our funding suggested PRE-LM as a promising phytobiotic against E. coli infection in mice.

Synthesized nanoliposome-encapsulated kaempferol attenuates liver health parameters and gene expression in mice challenged by cadmium-induced toxicity.

In the present research, we encapsulated a flavonoid called kaempferol into nanoliposomal structures and the health-promoting effects of synthesized nanoliposome-loaded kaempferol (NLK) were evaluated in mice challenged by cadmium-induced . The NLK characteristics, such as size, zeta potential, and polydispersity index, were 218.4 nm, -28.55 mV, and 0.29, respectively. The in vivo experiment revealed that the mice receiving water containing cadmium (2 mg/kg body weight/day) showed significant (p < 0.05) weight loss, an increase in liver enzyme activities, and hepatic oxidative stress. Dietary supplementation with NLK at concentrations of 2.5 and 5 mg/kg mice body weight notably (p < 0.05) improved the body weight, liver enzyme activities, hepatic oxidative stress, and antioxidant potential of the liver. Our findings elucidated that NLK could alleviate the toxicity of cadmium in mice challenged by cadmium-induced toxicity.

Nanoliposome-Loaded Phenolics from Nasturtium officinale Improves Health Parameters in a Colorectal Cancer Mouse Model.

Nasturtium officinale contains high amounts of phytochemical compounds that work against oxidative damages leading to improved health conditions in animals as well as humans. The study was performed to investigate the health benefits of nonencapsulated and nanoliposome-encapsulated phenolic rich fractions obtained from Nasturtium officinale on mice induced colorectal cancer. The experiment focused on encapsulation efficiency in improving the effectiveness of plant bioactive compounds. Phenolic rich fractions (PRF) were successfully loaded in the nanoliposome structure, a nanometer in size, of spherical shape and with homogeneous dispersion. Induction of colorectal cancer in mice impaired weight gain and feed intake, liver function and structural characteristics of ileum, while the dietary administration of nanoliposome-encapsulated PRF regulated the expression of Caspase 3, Bax, Bcl2, iNOS and SOD genes in the tumor tissue. The addition of nonencapsulated PRF and nanoliposome encapsulated PRF at the concentration of 100 mg TPC/kg BW/day improved the genes expression, although the nanoliposome-encapsulated PRF revealed better health outcomes compared to nonencapsulated PRF. Furthermore, both PRF improved intestinal morphology when the mice were challenged with colorectal cancer. The higher health promoting activity of nanoliposome-encapsulated PRF could be associated with its enhanced intestinal absorption, bioavailability, bioaccessibility and bioactivity. Consequently, the nanoliposome-encapsulated PRF could be considered as a promising anticancer agent against colorectal cancer.

Hepatoprotective effect of nanoniosome loaded Myristica fragrans phenolic compounds in mice-induced hepatotoxicity.

In this study, nanoniosome-loaded Myristica fragrans' (MF) phenolic compounds (NLMP) were synthesized and characterized for their physical properties, and hepatoprotective effects on mice with liver toxicity induced by L-asparaginase (LA) injection. According to the results, NLMP has a spherical shape with a 263 nm diameter, a zeta potential of -26.55 mV and a polydispersity index (PDI) of 0.192. The weight and feed intake of mice induced with hepatotoxicity were significantly (p ≤ 0.05) increased after they were treated with NLMP (2.5 mg/kg body weight of mice). In addition, the blood levels of triglyceride (TG), cholesterol (Chol), liver enzymes (aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP)) and total bilirubin were significantly (p ≤ 0.05) decreased. A significant increase (p ≤ 0.05) in the blood levels of the antioxidant defence system (glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT)) were also reported after NLMP treatment. NLMP was also led to a significant decrease (p ≤ 0.05) in inflammatory-related gene expression of inducible nitric oxide synthase (iNOS) and Interferon-gamma (IFN-γ) in the liver, as well as a meaningful (p ≤ 0.05) increase in the expression of SOD as an antioxidant status biomarker. Consequently, the NLMP is recommended as a potential dietary supplement to alleviate the symptoms of LA-induced hepatotoxicity.

Nano-liposomal encapsulation of Artemisia aucheri phenolics as a potential phytobiotic against Campylobacter jejuni infection in mice.

Background: Artemisia aucheri contains antibacterial phenolic compounds. The current work was implemented to evaluate the effectiveness of a nanoliposome-encapsulated phenolic-rich fraction (PRF-NLs), as a dietary phytobiotic derived from Artemisia aucheri's areal parts, on the inhibition of enteropathogenic Campylobacter jejuni (C. jejuni) infection in mice. Methods: The phenolic-rich fraction was loaded into the nanoliposome structure to obtain a nanometer-scale size liposome with homogenous dispersion. Next, 40 white male balb/c mice were assigned to 4 treatment groups. The PRF-NLs antibacterial potential was evaluated by evaluating the blood parameters, liver lipid peroxidation, and gene expression profiling in the mice challenged by C. jejuni infection. Results: Mice infected by C. jejuni showed impairment in food intake, weight gain, liver function, ileum morphometric features, and ileum tissue inflammation. The diet of fortified food with the nonencapsulated and nanoliposome-encapsulated phenolic compounds was found to improve these parameters at 10 mg TPC/kg BW/day concentration. Our data indicated that the nanoliposome-encapsulated PRF was more effective in promoting the health parameters in mice as compared to nonencapsulated PRF. Conclusion: It could be concluded that the liposomal encapsulation can promote the solubility, availability, and effectiveness of Artemisia aucheri phenolic compounds playing a key role as phytobiotic in mice intervened by enteropathogenic C. jejuni.

Zinc oxide nanoparticles synthesized using Hyssopus Officinalis L. Extract Induced oxidative stress and changes the expression of key genes involved in inflammatory and antioxidant Systems.

BACKGROUND: Recent advances in the synthesis of bioactive nanoparticles resulted in the discovery and introduction of new bioactive nanoparticles to the pharmaceutical industry. In this regard, this research is aimed to synthesize the zinc oxide nanoparticles (ZnO-NPs) using Hyssopus officinalis L. extract and to evaluate the safety of nanoparticles using Balb/C mice. METHODS: Forty male mice were divided into four groups and received 0, 50, 100, and 200 mg/kg of ZnO-NPs for thirty days. At the end of the experiment, blood sugar, creatinine, aspartate aminotransferase (A.S.T.), and alanine aminotransferase (A.L.T.) were determined. Furthermore, histopathological and oxidative stress biomarker analyses in liver and kidney tissues were performed. The changes in the major inflammatory- and antioxidant-related genes were determined. RESULTS: The results showed that blood sugar and creatinine reduced significantly (P < 0.05) when 50, 100, and 200 mg/kg ZnO-NPs were supplemented to the diet. The serum ALT and AST and lipid peroxidation in the liver and kidney tissues were increased significantly (p < 0.05) when 50, 100, and 200 mg/kg ZnO-NPs were supplemented to the diet. Supplementation of ZnO-NPs suppressed the expression of antioxidant-related genes (SOD and CAT) and up-regulated the inflammatory biomarkers (iNOS and TNF- α). The concentration of 200 mg/Kg nanoparticles indicated cellular degeneration and necrosis in the liver and kidney tissues. CONCLUSIONS: Overall, it can be concluded that supplementation of ZnO-NPs synthesized using Hyssopus Officinalis L. extract in this study at 50 mg/kg or higher concentrations might be toxic to the mice.

Heracleum persicum Essential Oil Nanoemulsion: A Nanocarrier System for the Delivery of Promising Anticancer and Antioxidant Bioactive Agents.

Essential oils are important compounds for the prevention and/or treatment of various diseases in which solubility and bio-accessibility can be improved by nanoemulsion systems. Heracleum persicum oil nanoemulsion (HAE-NE) was prepared and biological properties were investigated against human breast cancer cells and normal human fibroblasts foreskin. Particle size, zeta potential and poly dispersity index were 153 nm, −47.9 mV and 0.35, respectively. (E)anethole (57.9%), terpinolene (13.8%), É£-terpinene (8.1%), myrcene (6.8%), hexyl butyrate (5.2%), octyl butanoate (4.5%) and octyl acetate (3.7%) was detected in nanoemulsion. Proliferation of cancer cells at IC50 = 2.32 µg/mL was significantly (p < 0.05) inhibited, and cell migration occurred at 1.5 µL/mL. The HAE-NE at 1.5, 2.5 and 3.5 µg/concentration up-regulated caspase 3 and enhanced sub-G1 peak of cell cycle with nil cytotoxic effects in the liver, kidney and jejunum of mice. Villus height, villus width, crypt depth and goblet cells in mice group fed with 10 and 20 mg/kg body weight of HAE-NE improved. Cellular redox state in the liver indicated 10 and 20 mg/kg body weight of nanoemulsion significantly up-regulated the expression of SOD, CAT and GPx genes. Heracleum persicum oil nanoemulsion could be an eco-friendly nanotherapeutic option for pharmaceutical, cosmetological and food applications.

Chemical investigation and screening of anti-cancer potential of Syzygium aromaticum L. bud (clove) essential oil nanoemulsion.

This study was done to improve the medicinal properties of Syzygium Aromaticum L by processing S. Aromaticum L. bud essential oil (SABE) to the Nanoemulsion drug delivery system (SABE-NE) and investigating its anti-tumor and apoptotic impacts against the human HT-29 colon cancer cells. Applying the ultra-sonication method and characterization by DLS and FESEM analysis facilitates the nanoemulsification procedure. Human cancer (HT-29) and normal (HFF) cell lines were then evaluated based on the SABE-NE apoptotic and cytotoxic effects. In an in vitro section, flow cytometry method, Cas3 gene profile, AO/PI cell staining, and MTT assays are used to analyze the apoptotic and cytotoxic activities. In further analysis, liver lipid peroxidation and antioxidant genes expression (SOD, CAT, and GPx) investigate alterations in mice organs. As a result, produced 131.2 nm SABE-NE induces apoptosis response and cellular death (Cas3 up-regulation and enhanced SubG1 peaks). Subsequently, the HT-29 cells' viability can reduce significantly, while HFF cells indicate confined cytotoxic impacts. Moreover, in vivo test results on mice livers demonstrate the cytoprotective properties of SABE-NE (reduced lipid peroxidation and increased antioxidant enzymes gene expression and nondetectable cytotoxic impacts). We produced a novel nanoemulsion drug delivery system called SABE-NE, a cell-specific apoptotic inducer. We thus can be utilized as an efficient anti-cancer compound for human colon cancer treatment. However, further supplementary studies are required to verify and approve its cell-specific anti-tumor activity.

Rheum ribes extract-loaded nanoliposome as a novel phytogenic antibiotic alternative in mice challenged by Escherichia coli (O157:H7).

This study was performed to compare the noncapsulated with nanoliposome-encapsulated phenolic-rich fraction (PRF) obtained from Rheum ribes as a dietary additive and to assess their health-promoting potentials in the mice infected by enteropathogenic Escherichia coli (O157:H7). Upon fractionation, the ethyl acetate fraction with 46.9 ± 2.17 mg GAE/g DW was found as a highest phenolic content. The PRF successfully loaded into nanoliposome structure with a nanometer in size (193.2 nm) and spherical shape and homogeneous dispersion. The gallic acid, salicylic acid, caffeic acid, cinnamic acid, catechin, ellagic acid, and ferulic acid are bioactive phenolics present in the nanoliposome-loaded PRF; however, the main bioactive compounds are cinnamic acid (911 µg/g DW) and ellagic acid (826 µg/g DW). The infection caused by E. coil impaired the weight gain and food intake, liver function, morpho structural characteristics of jejunum, upregulated the expression of inflammatory genes (Cox2, iNOS), downregulation of antioxidant-related genes (SOD, GPX), and increased the ileal population of E. coil. The addition of nonencapsulated PRF and nanoliposome-encapsulated PRF at the concentration of 10 mg TPC/kg BW/day improved these parameters although the nanoliposome-encapsulated PRF revealed more potential as compared with the nonencapsulated PRF in improving the health parameters in mice. The higher health-promoting activity of nanoliposome-encapsulated PRF could be associated with its enhanced intestinal absorption, bioavailability, bioaccessibility, and bioactivity. Consequently, the nanoliposome-encapsulated PRF could be considered as a promising phytobiotic against E. coil infection in mice.

Antibacterial, Antioxidant and Melanogenesis Inhibitory Activity of Auraptene, a Coumarin from Ferula szowitsiana Root.

The auraptene is a geranyloxyn coumarin found in the Ferula species. The plant is endemic in Central Asia and it is used as a medicinal food in Iran. This research aimed to evaluate the antibacterial, antioxidant, and anti-melanogenic properties of auraptene, a coumarin from Ferula szowitsiana root. The results revealed that auraptene possessed antibacterial activity with minimum inhibitory and minimum bactericidal concentrations ranged from 2.5 up to 10 mg/ml against human pathogenic bacteria (Escherichia coli, Salmonella typhimurium, Salmonella paratyphi, Clostridium perfringens, Staphylococcus aureus). The nitric oxide scavenging activity (IC50: 670.9 µg/ml) showed its moderate antioxidant potential. Similarly, the results of ferric thiocyanate and thiobarbituric acid assays reconfirmed the moderate antioxidant activity of auraptene and indicated the percentage inhibitions of hydroxyl radicals to be 31.87 and 14%, respectively. The cell-based antioxidant evaluation confirmed the antioxidant activity of auraptene through up-regulation of the antioxidant-related genes including superoxide dismutase, catalase, and glutathione peroxidase in the human foreskin fibroblast (HFF). The auraptene has also displayed the anti-melanogenic activity through direct tyrosinase enzyme inhibition (IC50 of 29.7 µg/ml) and could modulate the expression of major melanogenesis-related genes including tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase in the murine melanoma cell line. The auraptene from Ferula szowitsiana root exhibited antibacterial, antioxidant, and melanogenesis inhibitory activities.

Zinc oxide nanoparticles synthesized using Hyssopus Officinalis L. Extract Induced oxidative stress and changes the expression of key genes involved in inflammatory and antioxidant Systems

BACKGROUND: Recent advances in the synthesis of bioactive nanoparticles resulted in the discovery and introduction of new bioactive nanoparticles to the pharmaceutical industry. In this regard, this research is aimed to synthesize the zinc oxide nanoparticles (ZnO-NPs) using Hyssopus officinalis L. extract and to evaluate the safety of nanoparticles using Balb/C mice. METHODS: Forty male mice were divided into four groups and received 0, 50, 100, and 200 mg/kg of ZnO-NPs for thirty days. At the end of the experiment, blood sugar, creatinine, aspartate aminotransferase (A.S.T.), and alanine aminotransferase (A.L.T.) were determined. Furthermore, histopathological and oxidative stress biomarker analyses in liver and kidney tissues were performed. The changes in the major inflammatory- and antioxidant-related genes were determined. RESULTS: The results showed that blood sugar and creatinine reduced significantly (P < 0.05) when 50, 100, and 200 mg/kg ZnO-NPs were supplemented to the diet. The serum ALT and AST and lipid peroxidation in the liver and kidney tissues were increased significantly (p < 0.05) when 50, 100, and 200 mg/kg ZnO-NPs were supplemented to the diet. Supplementation of ZnO-NPs suppressed the expression of antioxidant-related genes (SOD and CAT) and up-regulated the inflammatory biomarkers (iNOS and TNF- α). The concentration of 200 mg/Kg nanoparticles indicated cellular degeneration and necrosis in the liver and kidney tissues. CONCLUSIONS: Overall, it can be concluded that supplementation of ZnO-NPs synthesized using Hyssopus Officinalis L. extract in this study at 50 mg/kg or higher concentrations might be toxic to the mice.

Benefits and Challenges of Jatropha Meal as Novel Biofeed for Animal Production.

Jatropha curcas L. has gained importance as a source of seed oil for biodiesel production. The meal contained about 60% protein with a good balance of essential amino acids, containing various bioactive compounds, including saponins, phytic acids, trypsin inhibitors, lectins, phenolics, and flavonoids, which render it as a potential biofeed for animal production. The Jatropha meal demonstrated various biological activities, including antioxidant, antibacterial, and anti-inflammatory effects which enhance its property as a bio-feed. The levels of these bioactive compounds in the seeds are dependent on the genotypes. The J. curcas possessed different varieties which are either toxic or non-toxic according to the presence of phorbol esters. The presence of phorbol esters in the meal confirmed the toxic variety of Jatropha resulting in the limited application of meal as a biofeed. The Jatropha meal devoid of phorbol esters could be applied as a biofeed in the animal production industry, and for the toxic varieties, various techniques such as physicochemical and biological treatments have been introduced to the industry to remove the phorbol esters from Jatropha meal. Several studies employing various cells and animals confirmed the toxicity of the phorbol esters. The molecular mechanism of action of phorbol esters is through up-regulation of PKC-ß II gene, overexpression of down-stream proto-oncogenes resulted in inflammation and oxidative stress ending by apoptotic cell death. Despite the presence of valuable bioactive compounds in the Jatropha meal, its nutritional application is not recommended unless the phorbol esters are completely removed.

Amygdalus spinosissima root extract enhanced scopolamine-induced learning and memory impairment in mice.

The Amygdalus spinosissima (Rosaceae) plant has been used in the Iranian folk medicine as a remedy for the burn wound. Hence, in this study, we aimed to determine the possible medicinal potential of the plant focusing on the root part. The bioactive phenolic and flavonoid compounds present in the root extract of the Amygdalus spinosissima plant as well as its antioxidant and anti-inflammatory properties were determined. Moreover, the effects of root extract on learning and memory in mice were evaluated. The results revealed that the root methanolic extract contained phenolic and flavonoid compounds including apigenin, quercetin, rutin, kaempferol, gallic acid, syringic acid, ferulic acid, and ellagic acid. The extract possessed antioxidant, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activities in vitro. These biological activities were attributed to the presence of phenolics and flavonoids. The A. spinosissima root extract improved learning and memory function in scopolamine-induced memory dysfunction in mice as determined using the Morris water maze task. The extract modulated the AChE, BChE, and inflammatory genes and enhanced the expression of the antioxidant enzymes in the brain. Consequently, A. spinosissima root extract could be considered as a promising source of potent bioactive compounds in the retarding the development of neurodegenerative diseases such as Alzheimer's disease.

Manipulation of Rice Straw Silage Fermentation with Different Types of Lactic Acid Bacteria Inoculant Affects Rumen Microbial Fermentation Characteristics and Methane Production.

Bacterial inoculants are known to improve the quality of silage. The objectives of the present study were to evaluate the effects of different types of lactic acid bacteria (LAB; L. plantarum, L. salivarius, L. reuteri, L. brevi, and S. bovis) inoculation (106 cfu/ DM) on rice straw silage quality and to determine these effects on ruminal fermentation characteristics, digestibility and microbial populations in an in vitro condition. Inoculated rice straw was ensiled for 15 and 30 days. For the in vitro study, rumen fluid was obtained from three rumen-fistulated bulls fed on mixed forage and concentrate at 60:40 ratio twice daily. Inoculation with LAB improved (p < 0.05) the rice straw silage quality as indicated by higher dry matter and crude protein contents, decreased pH and butyric acid, and increased propionic acid and LAB numbers, especially after 30 days of ensiling. Results from the in vitro study revealed that starting with the addition of LAB to rice straw silage improved in vitro fermentation characteristics such as increased total volatile fatty acids and dry matter digestibility (p < 0.05). LAB treatments also decreased methane production and methane/total gas ratio after 15 and 30 days of ensiling. From the rumen microbial population perspective, cellulolytic, and fungal zoospores were enhanced, while protozoa and methanogens were decreased by the LAB treatments. Based on these results, it could be concluded that inoculating rice straw silage with LAB (especially for L. plantarum and S. bovis) improved silage quality, rumen fermentation parameters and microbial populations in vitro.

Ferutinin: A phytoestrogen from ferula and its anticancer, antioxidant, and toxicity properties.

This study was performed to evaluate the antioxidant, anticancer, and toxicity properties of ferutinin, a phytoestrogen derived from Ferula species. The human Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line and normal human fibroblast (HDF) were cultured and treated with different ferutinin concentrations. The cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell death-defining tests (a comparative real-time polymerase chain reaction [for Bax and Bcl-2 genes], flow cytometry, and acridine orange/propidium iodide cell staining). Moreover, 15 white male balb/c mice were divided into three groups of five (one untreated control group and two groups), which received different doses of ferutinin-supplemented water (500 and 1000 µg/kg mice weight) to check the mice liver and kidney pathomorphological alterations and to determine the antioxidant enzymes' expression profile (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase) in the mentioned tissues. Finally, the liver lipid peroxidation of mice was analyzed. The results of MTT and cell death-defining tests indicate the significant reduction in cell viability and induction of apoptotic death in MCF-7 cells (enhanced sub-G1 peaks, Bax overexpression, Bcl-2 downregulation, and increased apoptotic cells). The antioxidant enzymes (SOD and CAT) in the mice liver and kidney cells were found to be upregulated (p < .05) in response to the increasing doses of ferutinin. Besides, the lipid peroxidation of the liver tissue of mice was significantly reduced. According to the results, we suggest that ferutinin has the potential to be served as a selective anticancer compound for breast cancer treatment.