Modulation of ACE2/Ang1-7/Mas and ACE/AngII/AT1 axes affects anticancer properties of sertraline in MCF-7 breast cancer cells.

The renin-angiotensin system (RAS) is best known for playing a major role in maintaining the physiology of the cardiovascular system. Dysregulation of the RAS pathway has been proposed as a link to some malignancies and contributes to cancer metastasis. Breast cancer is considered as one of the leading causes of cancer death in women and its prevention remains yet a challenge. Elements of RAS are expressed in both normal breast tissue and cancerous cells, signifying the essential role of RAS in breast cancer pathology. Sertraline, a widely used antidepressant, has shown anti-proliferative properties on a variety of malignancies. This study aimed to investigate the effect of sertraline and its combination with agonists and antagonists of RAS (A779, Ang 1-7 and losartan) on viability of MCF-7 cells along with their effect on apoptosis and distribution of cell cycle. Our results indicated that sertraline, losartan and Ang 1-7 significantly decreased cell viability, induced apoptosis and cell cycle arrest. A779 blunted the effect of sertraline on cell viability, ROS generation and cell cycle arrest. Combination treatment of sertraline with losartan as well as Ang 1-7 caused a remarkable decline in cell viability. In conclusion, results of the present study support the anti-cancer properties of sertraline, losartan and Ang 1-7 via induction of apoptosis and cell cycle arrest.

Application of novel metal organic framework-deep eutectic solvent/molecularly imprinted polymer multiple monolithic fiber for solid phase microextraction of amphetamines and modafinil in unauthorized medicinal supplements with GC-MS.

The goal of this research is the development of multiple monolithic fiber-solid phase microextraction (MMF-SPME) using a new integrated fiber for the determination of amphetamine derivatives and modafinil from unauthorized medicinal supplements. For this purpose, a monolithic fiber of metal organic framework MIL-Al (53)-deep eutectic solvent (DES)/molecularly imprinted polymers (MOF-DES/MIP) was synthesized. To find optimum microextraction conditions gas chromatography-mass spectrometer (GC-MS) was used and the influences of effective variables were investigated using one factor at a time method. After that, the significant variables were optimized using a Box-Behnken design (BBD) combined with a desirability function (DF). Under optimized conditions (desorption solvent=1500 µL of 1-octanol, pH=3.5, extraction time=35 min, [NaCl]=0% w/v and stirring rate=600 rpm), calibration graphs of analytes were linear in a concentration range of 0.1-400 µg L-1 with correlation coefficients > 0.9966. Limits of detection and quantification were in the ranges of 0.023-0.033 µg L-1 and 0.088-0.113 µg L-1, respectively. This procedure was successfully employed in determining target analytes in spiked and unspiked unauthorized medicinal supplement samples with recoveries ranging from 95.14 to 104.63%.

Comparison of Protective Effects of Phenolic Acids on Protein Glycation of BSA Supported by In Vitro and Docking Studies.

Several diabetic complications are associated with forming advanced glycation end products (AGEs). Different chemical and natural compounds are able to prevent the development of these products. In this study, glycosylation was induced as a model by incubating bovine serum albumin (BSA) with glucose. Consequently, BSA was treated with glucose and different concentrations (1.25, 2.5, and 5 µM) of syringic acid, gallic acid, ellagic acid, ferulic acid, paracoumaric acid, and caffeic acid for 4 and 6 weeks. Biochemical experiments comprise measurements of fluorescent AGEs, protein carbonyl contents, total thiol, hemolysis tests, and also malondialdehyde (MDA) levels in RBC. These demonstrated the antiglycating mechanism of these phenolic acids. Most of the phenolic acids used in this study reduced MDA levels and protected thiol residues in protein structures. They also inhibited the formation of fluorescent AGEs and RBC lysis, except gallic acid. Moreover, ferulic acid, paracoumaric acid, and caffeic acid proteins significantly prevent carbonylation. Molecular docking and simulation studies showed that ellagic, caffeic, gallic, and syringic acids could interact with lysine and arginine residues in the active site of BSA and stabilize its structure to inhibit the formation of AGEs. Our results suggest that phenolic acid could be used as a potential phytochemical against protein glycation and related diabetic complications.

Metformin enhances anti-cancer properties of resveratrol in MCF-7 breast cancer cells via induction of apoptosis, autophagy and alteration in cell cycle distribution.

Breast cancer is the fifth leading cause of death, worldwide affecting both genders. Accumulating evidence suggests that metformin, an oral hypoglycemic agent used in the management of type 2 diabetes, exerts anti-tumor effects in many cancers, including the breast cancer. Resveratrol, a natural product found abundantly in many fruits, exhibits marked cytotoxic and pro-oxidant effects. This study was designed to investigate the effect of metformin in combination with resveratrol and cisplatin in MCF-7 cells. Study groups were as follows: untreated control group, single treatment groups (metformin, resveratrol, and cisplatin), double treatment groups (metformin + resveratrol, metformin + cisplatin, and cisplatin + resveratrol) and triple treatment groups (metformin + resveratrol + cisplatin). Our results indicated that metformin inhibits proliferation of MCF-7 cells, an effect that was associated with ROS production and G0/G1 cell cycle arrest, but not apoptosis. Moreover, resveratrol suppressed the proliferation of MCF-7 cells by induction of apoptosis as well as cell cycle arrest. Notably, a significant inhibitory effect in the co-treatment of metformin, resveratrol, and cisplatin was observed which was attributed to induction of autophagy-mediated cell death and apoptosis along cell cycle arrest. In conclusion, our results advocate the anti-cancer properties of metformin and resveratrol on MCF-7 cell s via induction of cell cycle arrest. Additionally, synergistic anti-cancer effects of metformin in a triple combination with cisplatin and resveratrol was attributed to induction of autophagy-mediated cell death and apoptosis along cell cycle arrest. Based on our findings it is proposed that patients may benefit from addition of a drug with a safe profile to conventional anticancer therapies.

Combination of metformin and gallic acid induces autophagy and apoptosis in human breast cancer cells.

Background and purpose: Breast cancer is the most common type of cancer and one of the major causes of death among women. Many reports propose gallic acid as a candidate for cancer treatment due to its biological and medicinal effects as well as its antioxidant properties. This study aimed to assess the effects of metformin and gallic acid on human breast cancer (MCF-7) and normal (MCF-10) cell lines. Experimental approach: MCF7 and MCF-10 cells were treated with various concentrations of metformin, gallic acid, and their combination. Cell proliferation, reactive oxygen species (ROS), as well as cell cycle arrest were measured. Autophagy induction was assessed using western blot analysis. Findings/Results: Metformin and gallic acid did not cause toxicity in normal cells. They had a stronger combined impact on ROS induction. Metformin and Gallic acid resulted in cell cycle arrest in the sub-G1 phase with G1 and S phase arrest, respectively. Increased levels of LC3 and Beclin-1 markers along with decreased P62 markers were observed in cancerous cells, which is consistent with the anticancer properties of metformin and gallic acid. Conclusion and implications: The effects of metformin and gallic acid on cancerous cells indicate the positive impact of their combination in treating human breast cancer.

Antioxidant and anticholinesterase properties of Echinometra mathaei and Ophiocoma erinaceus venoms from the Persian Gulf.

Introduction: The Persian Gulf is home to a diverse range of marine life, including various species of fish, crustaceans, mollusks, and echinoderms. This study investigates the potential therapeutic properties of venoms from echinoderms in the Persian Gulf, specifically their ability to inhibit cholinesterases (Acetylcholinesterase and butyrylcholinesterase) and act as antioxidants. Methods: Four venoms from two echinoderm species, including the spine, gonad, and coelomic fluids of sea urchins, as well as brittle star venoms, were analyzed using various methods, including LD50 determination, protein analysis, antioxidant assays, GC-MS for secondary metabolite identification, and molecular docking simulations. Results and discussion: The study's results revealed the LD50 of the samples as follows: 2.231 ± 0.09, 1.03 ± 0.05, 1.12 ± 0.13, and 6.04 ± 0.13 mg/mL, respectively. Additionally, the protein levels were 44.037 ± 0.002, 74.223 ± 0.025, 469.97 ± 0.02, and 104.407 ± 0.025 µg/mL, respectively. SDS-PAGE and total protein studies indicated that at least part of the venom was proteinaceous. Furthermore, the study found that the brittle star samples exhibited significantly higher antioxidant activity compared to other samples, including the standard ascorbic acid, at all tested concentrations. GC-MS analysis identified 12, 23, 21, and 25 compounds in the samples, respectively. These compounds had distinct chemical and bioactive structures, including alkaloids, terpenes, and steroids. Conclusion: These venoms displayed strong cholinesterase inhibitory and antioxidant activities, likely attributed to their protein content and the presence of alkaloids, terpenes, and steroids. Notably, the alkaloid compound C 7 was identified as a promising candidate for further research in Alzheimer's disease therapy. In conclusion, echinoderms in the Persian Gulf may hold significant potential for discovering novel therapeutic agents.

Antidotal effect of dihydroxyacetone against phosphine poisoning in mice.

Phosphine (PH3 ) is widely used as an insecticide and rodenticide. On the contrary, many cases of PH3 poisoning have been reported worldwide. Unfortunately, there is no specific antidote against PH3 toxicity. Disruption of mitochondrial function and energy metabolism is a well-known mechanism of PH3 cytotoxicity. Dihydroxyacetone (DHA) is an adenosine triphosphate supplying agent which significantly improves mitochondrial function. The current study was designed to evaluate DHA's effect on inhalational PH3 poisoning in an animal model. DHA was injected into BALB/c mice before and/or after the start of the PH3 inhalation. The cytochrome c oxidase activity was assessed in the animals' brain, heart, and liver exposed to PH3 (for 15, 30, and 60 min, with and without the antidote). The LC50 of PH3 was calculated to be 18.02 (15.42-20.55) ppm over 2 h of exposure. Pretreatment of DHA (1 or 2 g/kg) increased the LC50 of PH3 by about 1.6- or 3-fold, respectively. Posttreatment with DHA (2 g/kg) increased the LC50 of PH3 by about 1.4-fold. PH3 inhibited the activity of cytochrome c oxidase in the assessed organs. It was found that DHA treatment restored mitochondrial cytochrome c oxidase activity. These findings suggested that DHA could be an effective antidote for PH3 poisoning.

The Effect of a Traditional Preparation Containing Piper nigrum L. and Bunium persicum (Boiss.) B.Fedtsch. on Immobility Stress-Induced Memory Loss in Mice.

OBJECTIVE: Alzheimer's disease is a progressive, age-related, and neurodegenerative disease characterized by mental decline. The exact cause of Alzheimer's disease is unclear, but cholinergic dysfunction, protein accumulation, and oxidative stress are among the most important hypotheses. The main purpose of our study was to investigate the effects of aqueous and hydroalcoholic extract combination of these two medicinal plants, black pepper and cumin (as a related formulation in traditional Persian medicine), on memory and learning of an immobilized stress animal model. METHODS: In this study, hydroalcoholic and aqueous extracts of cumin and black pepper fruits were prepared. Six groups of mice were treated orally for 2 weeks: control group, immobility stress, and stress-induced immobility mice received different doses of the hydroalcoholic extract (100 and 200 mg/kg) and aqueous extract (100 and 200 mg/kg). The shuttle box, novel object detection, and rotarod test were used to evaluate memory and learning. The activities of acetylcholinesterase, catalase (CAT), and superoxide dismutase (SOD) and the level of reduced glutathione (GSH) and malondialdehyde (MDA) were measured in the brain tissue. RESULTS: Immobility stress significantly reduced learning and motor coordination. Furthermore, MDA levels and acetylcholinesterase activity were significantly increased, while CAT and SOD activities were significantly reduced in the brain of immobility-induced stress mice. Other findings indicated that hydroalcoholic and aqueous extracts (100 and 200 mg/kg) of cumin and black pepper fruits have an improving effect on animal motor coordination and learning ability, GSH content, and CAT, SOD, and acetylcholinesterase enzyme function in comparison with stress groups (p < 0.05). CONCLUSION: The hydroalcoholic and aqueous extracts of cumin and black pepper fruits have protective effects against stress-induced memory deficit and oxidative stress and may have beneficial therapeutic effect in the treatment of neurodegenerative diseases.

Syringic Acid: A Potential Natural Compound for the Management of Renal Oxidative Stress and Mitochondrial Biogenesis in Diabetic Rats.

BACKGROUND: Diabetic nephropathy can lead to renal diseases; oxidative stress and mitochondrial dysfunction have critical roles in its development. OBJECTIVES: In this study, the effect of syringic acid (SYR), a natural phenolic acid, on diabetic nephropathy and mitochondrial biogenesis was examined. METHODS: Diabetes was induced in rats by injecting streptozotocin. SYR (25, 50 and 100 mg/kg/day) was orally administered for 6 weeks. SYR effects on factors, such as antioxidant activities and mRNA expression level of mitochondrial biogenesis indexes, were evaluated. RESULTS: In SYR-treated rats, blood glucose and ALP level were significantly reduced. SYR increased kidney GSH content in the diabetic group. Elevated renal catalase and superoxide dismutase activities in diabetic rats were restored to normal levels after treatment. SYR significantly reduced the renal TBARS level, which had increased in diabetic rats. This compound also significantly upregulated renal mRNA expression of PGC-1α and NRF-1, and increased mtDNA/nDNA ratio in diabetic rats. These values were reduced in the non-treated diabetic group. The results show improvement of histopathological damages of kidney in the SYR treated group in comparison with the diabetic group. CONCLUSION: According to the results, SYR alters renal antioxidant defense mechanisms. Also, it could be considered as a novel approach by targeting mitochondria in renal diabetic complications.

Syringic Acid Attenuates Cardiomyopathy in Streptozotocin-Induced Diabetic Rats.

OBJECTIVES: Diabetic cardiomyopathy (DC) has become one of the serious complications in diabetic cases. In this study, we aimed to explore the syringic acid (SYR) protective effect against diabetes-induced cardiac injury in experimental rats. METHODS: Rats were divided in control and streptozotocin-induced diabetic rats which were subdivided into diabetic controls, and three test groups (SYR at 25, 50, and 100 mg/kg) and the nondiabetic group received 100 mg/kg of SYR. All treatments were given SYR for 6 weeks. SYR effects on cardiac diagnostic markers, heart lipid peroxidation, protein carbonylation, antioxidant system, and changes of the heart mitochondrial mass and biogenesis were measured. RESULTS: Diabetes induction prompted CK-MB, LDH levels in serum, cardiac catalase, and superoxide dismutase activity, as well as cardiac TBARs and carbonylated protein. SYR administration (100 m/kg) attenuated CK-MB and LDH levels. Also, 50 and 100 mg/kg of SYR reduced cardiac TBARs and carbonylated protein in diabetic rats. These treatments did not show any effects on GSH content, mtDNA, and mitochondrial biogenesis indices (PGC1- α, NRF1, NRF2, and TFAM) in heart tissue. CONCLUSIONS: SYR treatment showed protective effects on diabetic cardiomyopathy in rats by reducing lipid peroxidation and protein carbonylation. The possible mechanisms could be related to antioxidant activity of this phenolic acid. SYR might play a role of a protective factor in cardiac challenges in diabetes.

The effect of ellagic acid on spinal cord and sciatica function in a mice model of multiple sclerosis.

Multiple sclerosis (MS) is a well-known neurodegenerative disorder, causing toxicity in different organs, such as spinal cord tissue. The goal of this study was to investigate the protective effect of ellagic acid (EA) against spinal cord and sciatica function in cuprizone (Cup)-induced demyelination model. Animals were divided into six equal groups. The first group received tap water as the control. Cup group was treated with Cup (0.2% w/w in fed). EA 100 group was orally treated with EA (100 mg/kg). EA + Cup groups were orally treated with three doses of 5, 50, and 100 mg/kg of EA plus Cup (0.2% w/w). All groups received treatment for 42 days. Open field, rotarod, and gait tests were done to evaluate the behavioral changes following Cup and/or EA treatment. Also, lipid peroxidation, reactive oxygen species (ROS) content, antioxidant capacity, superoxide dismutase (SOD), and catalase enzymes activity in spinal cord was evaluated. Luxol fast blue (LFB) staining also the behavioral tests were performed to evaluate the model. Cup increased ROS levels and oxidative stress in their spinal cord tissues. Also, Cup reduced antioxidant capacity, SOD, and catalase activity. EA (especially at 100 mg/kg) prevented these abnormal changes. EA co-treatment dose-dependently was able to ameliorate behavioral impairments in mice that received Cup. EA might act as a protective agent in MS by modulating spinal cord function.

A systematic review on the genotoxic effect of serotonin and norepinephrine reuptake inhibitors (SNRIs) antidepressants.

RATIONALE: Depression is a major mental disorder affecting millions of people worldwide. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are one of the antidepressant drugs prescribed for depression treatment. OBJECTIVE AND METHOD: There are many contradiction studies about the adverse effect and genotoxicity of SNRIs. So here, based on the guidelines proposed at the PRISMA statement, we performed a quantitative systematic review by searching international electronic databases (PubMed, Scopus, Embase, and Web of Science) for published documents on SSNRIs and their genotoxicity effects. RESULTS: The database searches retrieved 336 records, 18 of which met the inclusion criteria. Evaluation of the selected articles showed that a total of 9 articles were appropriate for final review. Most of these studies (78%) reported positive results for the genotoxicity of SNRIs CONCLUSION: Finally, we can conclude that these drugs have the potential to damage DNA.

Neuroprotective Effect of Syringic Acid by Modulation of Oxidative Stress and Mitochondrial Mass in Diabetic Rats.

Diabetes is a metabolic complaint associated with oxidative stress and dysfunction of mitochondria. One of the most common complications of diabetes mellitus is neuropathy. This study evaluated the possible neuroprotective effects of syringic acid (SYR), a natural polyphenolic derivative of benzoic acid, on oxidative damage and mitochondria in the brain, spinal cord, and sciatic nerve of streptozotocin-induced diabetic rats. Different groups of rats including normal control, diabetics (induced by streptozotocin), diabetic groups treated with 25, 50, and 100 mg/kg of SYR, and non-diabetic group treated with only 100 mg/kg of SYR were treated for 6 weeks. Learning and memory function, physical coordination, and acetylcholinesterase (AChE) and antioxidant indexes, as well as mRNA expression of mitochondrial biogenesis, were measured in the brain, spinal cord, and sciatic nerves. Diabetic rats treated with 100 mg/kg SYR exhibited significantly improved learning, memory, and movement deficiency (p < 0.05). SYR 100 mg/kg also significantly upregulated the brain mRNA expression of PGC-1α and NRF-1, the key regulators of energy metabolism, oxidative phosphorylation, and mitochondrial biogenesis. In addition, SYR 100 mg/kg and SYR 50 mg/kg increased the mtDNA/nDNA ratio in the brain and the spinal cord of diabetic rats, respectively (p < 0.05). SYR attenuated the lipid peroxidation in all the tissues, but not significant effects were observed on GSH, AChE, catalase, and superoxide dismutase activity. In all the tests, nonsignificant differences were observed between the control and SYR 100 mg/kg groups. Moreover, SYR reduced inflammation and demyelination in sciatic nerves. This is the first study to reveal the regulation of mitochondrial biogenesis and energy metabolism by SYR, beyond its antioxidant role in the diabetic rats' brain and spinal tissues.

Syringic acid improves oxidative stress and mitochondrial biogenesis in the liver of streptozotocin-induced diabetic rats

Objective: To determine the effects of syringic acid on hepatic damage in diabetic rats.Methods: Diabetes was induced by streptozotocin. Diabetic rats were given syringic acid at doses of 25, 50 and 100 mg/kg by oral gavage for 6 weeks. Syringic acid effects on the liver were evaluated by examination of plasma biochemical parameters, and pathological study. In addition, biomarkers of lipid peroxidation and antioxidant status of liver tissues were assessed. Real time-PCR was performed to investigate the mRNA expression levels of mitochondrial biogenesis indices in different groups. Results: Syringic acid significantly attenuated the increase in most of plasma biochemical parameters in diabetic rats. Moreover, syringic acid treatment increased the catalase activity while it reduced the superoxide dismutase activity and hepatic malondialdehyde level in diabetic rats. There was no difference between the glutathione content of the treated and untreated groups. These findings were supported by alleviation of histopathological damages in the syringic acid-treated groups compared to the untreated diabetic group. Syringic acid also significantly up-regulated the hepatic mRNA expression of PGC-1α, NRF-1, and NRF-2 and increased the mtDNA/nDNA ratio in diabetic rats. Conclusions: Syringic acid can be considered as a suitable candidate against hepatic complications since it can reduce oxidative damages in diabetic cases. Furthermore, it has the potential of targeting hepatic mitochondria in diabetes.

Ellagic acid improves muscle dysfunction in cuprizone-induced demyelinated mice via mitochondrial Sirt3 regulation.

Sirt3 enzyme and mitochondrial abnormality can be related to excess fatigue or muscular dysfunction in multiple sclerosis (MS).Ellagic acid (EA) has a mitochondrial protector, iron chelator, antioxidant, and axon regenerator in neurons.In this study the effect of EAon muscle dysfunction, its mitochondria, and Sirt3 enzyme incuprizone-induced model of MSwas examined. Demyelination was induced by a diet containing 0.2% w/w cuprizone (Cup) for 42 days and EA administered daily (5, 50, and 100 mg/kg P.O) either with or without cuprizone in mice. Behavioral tests were assessed, and muscle tissue markers ofoxidative stress, mitochondrial parameters, mitochondrial respiratory chain activity, the Sirt3 protein level, and Sirt3 expression were also determined. Luxol fast blue staining and the behavioral tests were performed toassess the implemented model. In Cup group an increased oxidative stress in their muscle tissues was observed. Also, muscle mitochondria exhibited mitochondria dysfunction, lowered mitochondrial respiratory chain activity, Sirt3 protein level, and Sirt3 expression.EA prevented most of these anomalous alterations. Sub-chronicEA co-treatment dose-dependently ameliorated behavioral and muscular impairment in mice that received Cup.EA can effectively protect muscle tissue against cuprizone-induced demeylination via the mitochondrial protection, oxidative stress prevention and Sirt3 overexpression.

The effects of crocin on spatial memory impairment induced by hyoscine: Role of NMDA, AMPA, ERK, and CaMKII proteins in rat hippocampus.

OBJECTIVES: Crocus sativus L. and its active constituent, crocin, have neuroprotective effects. The effects of crocin on memory impairment have been mentioned in studies but the signaling pathways have not been evaluated. Therefore, the aim of this study was to evaluate the effects of crocin on the hyoscine-induced memory impairment in rat. Additionally, the level of NMDA (N-methyl-D-aspartate receptors), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicd acid), ERK (extracellular signal-regulated kinases), CaMKII (calcium (Ca2+)/calmodulin (CaM)-dependent kinaseII) mRNA and proteins were determined in rat hippocampus. MATERIALS AND METHODS: Crocin (10, 20, and 40 mg/kg), hyoscine (1.5 mg/kg), normal saline and rivastigmine were administered intraperitoneally to male Wistar rats for 5 days. The effects on memory improvement were studied using Morris water maze (MWM) test. Then, the protein levels of NMDA, AMPA, ERK, pERK, CaMKII and p.CaMKII in hippocampus were analized using the Western blot test. Furthermore, the mRNA levels of NMDA, AMPA, ERK and pCaMKII genes were evaluated using real-time quantitative reverse transcription-polymerase chain reaction (qRT- PCR) method. RESULTS: Aadminestration of crocin (20 mg/kg) and rivastigmine significantly improved learning and memory impairment induced by hyoscine. Also, administration of hyoscine reduced protein level of pERK, while treatment with crocin (20 mg/kg) recovered the protein level. No changes were observed in the protein levels and mRNA gene expression of NMDA, AMPA, ERK, CaMKII and pCaMKII following adminestration of hyoscine or crocin. CONCLUSION: Adminestration of crocin improved memory and learning. The effect of crocin in this model can be mediated by alteration in pERK protein level in rat hippocampus.

Glycyrrhizic Acid Ameliorates Mitochondrial Function and Biogenesis Against Aluminum Toxicity in PC12 Cells.

Glycyrrhizic acid (GA) is the most effective ingredient in the root of licorice, with important pharmacological effects. We investigate the effects of GA on mitochondrial function and biogenesis in the aluminum toxicity in PC12 cell line. After pretreatment of PC12 cells with different concentrations of GA (5-100 µM), and specific concentration of aluminum maltolate (Almal,1000 µM) for 48 h, cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondria mass, cytochrome c oxidase enzyme activity, and the ATP level of the cells were measured. The expression mRNA level of PGC-1α, NRF1, NRF2, and TFAM was confirmed by the real-time PCR quantitative method. The results showed that low concentrations of GA protected Almal-induced cell death in 48 h. It was also observed that GA reduced the ROS production and increased the ATP level. The activity of cytochrome c oxidase enzyme and also decrease of MMP were improved. In addition, GA significantly increased the expression of mitochondrial genes and mass against aluminum toxicity. GA can exert its protective effect against the toxicity of Almal through maintaining mitochondrial function and subsequently increasing energy metabolism and mitochondrial biogenesis. GA as a natural product can be considered as a supplement in neurodegenerative disease.

Design and development of vitamin C-encapsulated proliposome with improved in-vitro and ex-vivo antioxidant efficacy.

Vitamin C, as an antioxidant additive in pharmaceutical and food products, is susceptible to environmental conditions, and new design strategies are needed to enhance its stability. The aim of this study is to prepare vitamin C proliposome using film deposition on the carrier by applying different factors, and optimise the characteristics of the obtained powder using the design expert® software. The optimised formulation demonstrated acceptable flowability with 20% vitamin C loading. This formulation released about 90% vitamin C within 2 h and showed higher (1.7-fold) in-vitro antioxidant activity. Ex-vivo antioxidant activity was 1.9 and 1.6 times higher in brain and liver cells, respectively. A 27% reduction in malondialdehyde (MDA) level of liver cell was obtained comparing free vitamin C. Therefore, this study results suggest that the vitamin C-encapsulated proliposome powder might be an appropriate carrier for oral drug delivery of vitamin C with better antioxidant efficacy.

Effects of sodium benzoate, a commonly used food preservative, on learning, memory, and oxidative stress in brain of mice.

Sodium benzoate (SB) is a widely used preservative and antimicrobial substance in many foods and soft drinks. However, this compound is generally recognized as safe food additives, but evidence has suggested that a high intake of SB may link to attention deficit-hyperactivity disorder in children. Present study investigate the effects of oral administration of different concentrations of SB (0.56, 1.125, and 2.25 mg/mL) for 4 weeks, on the learning and memory performance tests, and also the levels of malondialdehyde (MDA), reduced glutathione (GSH), and acetylcholinesterase activity (AChE) in the mouse brain. The results showed that SB significantly impaired memory and motor coordination. Moreover, SB decreased reduced GSH and increased the MDA level in the brain significantly (P < 0.001). However, nonsignificant alteration was observed in the AChE activity. These findings suggest that short-term consumption of SB can impair memory performance and increased brain oxidative stress in mice.

The protective effect of sodium benzoate on aluminum toxicity in PC12 cell line.

Sodium benzoate (SB) is one of the food additives and preservatives that prevent the growth of fungi and bacteria. SB has been shown to improve the symptoms of neurodegenerative disease such as Alzheimer's disease. The aim of this study was to evaluate the effect of SB on the cell survival and cellular antioxidant indices after exposure to aluminum maltolate (Almal) in PC12 cell line as a model of neurotoxicity. The cells exposed to different concentrations of SB (0.125 to 3 mg/mL) in the presence of Almal (500 µM) and cell viability, the level of reactive oxygen species (ROS), glutathione content and catalase activity were measured. The results showed that low concentrations of SB caused an increase in the cell survival, but cell viability was reduced in high concentrations. SB could neither prevent the level of ROS production nor change glutathione content. SB (0.5 mg/mL) significantly increased the catalase enzyme activity as compared to the Almal. This study suggested that SB did not completely protect the cell to aluminum-induced free radicals toxicity. Possibly SB improves the symptoms of neurodegenerative disease by other mechanisms.