Urtica pilulifera L. seed extract promotes folliculogenesis and alleviates the diminished ovarian reserve in the Balb/c mice model: An experimental study.

Background: Urtica pilulifera L. seed (UPS) is a Persian traditional medicine prescription that positively affects female infertility. Objective: This study aimed to evaluate the beneficial effects of UPS on a diminished ovarian reserve (DOR) model induced by cyclophosphamide in Balb/c mice. Materials and Methods: A single intraperitoneal (75 mg/kg) of cyclophosphamide was administered to establish a DOR model. 25 female Balb/c mice (6-8 wk, 25 ± 2 gr) were randomly divided into 5 groups (n = 5/each), including control (normal saline), model (DOR), DOR+50, DOR+100, and DOR+200 (mg/kg UPS, gavage) groups for 14 days. The levels of follicle-stimulating hormone, luteinizing hormone, estradiol, malondialdehyde, superoxide dismutases, apoptosis, and histopathological alterations were analyzed. Gas chromatography-mass spectrometry analysis was performed to identify the phytochemicals of the UPS. Results: It was observed that the UPS extract reduced malondialdehyde concentration and apoptosis in the DOR model as well as enhanced superoxide dismutases activity in the ovaries in a dose-dependent manner. Moreover, it exerted a modulatory effect on steroidal hormones such as follicle-stimulating hormone, luteinizing hormone, and estradiol. The histopathological analysis revealed the therapeutic potential of the UPS extract. The main chemical components of UPS were linoleic acid (59.25%), n-hexadecanoic acid (10.36%), and oleic acid (8.29%). Conclusion: The results indicated that the UPS extract has therapeutic potential in the DOR model. This potential is attributed to the reduction of oxidative stress, modulation of apoptosis, and regulation of steroidal hormones that may be associated with the observed beneficial effects of fatty acids on fertility improvement.

Polysaccharide-based hydrogels containing herbal extracts for wound healing applications.

Development of an ideal wound dressing with effective function for healing various types of wounds is the ultimate desire of the researchers. Natural-based compounds such as polysaccharides and phytochemicals offer useful properties making them perfect candidates for wound management. Polysaccharides-based hydrogels with an interconnected three-dimensional network, and desired properties have great potential as a carrier for delivery of different herbal extracts for oral and topical applications. Herbal extracts are extensively used for wound healing purposes, individually or in combination with other active agents. This study summarizes the current knowledge acquired on the preparation, functionalizing, and application of different kinds of polysaccharide-based hydrogels enriched by herbal extracts for different wound healing applications. The structural, biological, and functional impact of the polysaccharides and herbal extracts on the final hydrogel characteristics, as well as their influence on the different phases of the wound healing process have been discussed.

The effects of all trans retinoic acid, vitamin D3 and their combination on plasma levels of miRNA-125a-5p, miRNA-34a, and miRNA-126 in an experimental model of diabetes.

OBJECTIVE: The purpose of this study was to evaluate the effects of ATRA (all trans retinoic acid), vitamin D3, and their combination on circulating levels of miR (MicroRNA) -125a-5p, miR-126, and miR-34ain diabetic rats. MATERIALS AND METHODS: Total miRNA was extracted from plasma samples. miRNA expression profiles of 30 rats in five groups were analyzed after 4-week intervention. The expression levels of miRNAs were measured using qRT-PCR. RESULTS: We analyzed the expression of miR-126, miR-125a-5p, and miR-34a in serum among all five groups (p=0.268). The levels of miRNA-126 (p=0.004) and miR-125a-5p (p=0.014) showed a significant difference among our experimental groups. The circulating levels of miR-126 decreased in DC (Diabetic control) group compared to the HC (Healthy control) group (p=0.009). In addition, vitamin D3+ATRA supplementation increased miR-126 expression (p=0.014). Moreover, the levels of miR-125a-5p decreased in the DC group compared to the HC group (p=0.019). CONCLUSION: The expression of miR-126 and miR-125a-5p decreased in diabetic rats. Also, vitamin D3+ATRA can be considered a new therapeutic agent that can elevate miR-126 expression and prevent diabetes-related cardiovascular complications.

Preparation of Polyurethane/Pluronic F127 Nanofibers Containing Peppermint Extract Loaded Gelatin Nanoparticles for Diabetic Wounds Healing: Characterization, In Vitro, and In Vivo Studies.

Diabetic ulcer is regarded as one of the most prevalent chronic diseases. The healing of these ulcers enhances with the use of herbal extracts containing wound dressings with high antibacterial property and creating a nano-sized controlled release system. In this study, new peppermint extract was incorporated in the polyurethane- (PU-) based nanofibers for diabetic wound healing. The peppermint extract was used as an herbal antimicrobial and anti-inflammatory agent. The absorption ability of the wound dressing was enhanced by addition of F127 pluronic into the polymer matrix. The release of the extract was optimized by crosslinking the extract with gelatin nanoparticles (CGN) and their eventual incorporation into the nanofibers. The release of the extract was also controlled through direct addition of the extract into the PU matrix. The results showed that the release of extract from nanofibers was continued during 144 hours. The prepared wound dressing had a maximum absorption of 410.65% and an antibacterial property of 99.9% against Staphylococcus aureus and Escherichia coli bacteria. An in vivo study indicated on significant improving in wound healing after the use of the extract as an effective compound. On day 14, the average healing rate for samples covered by conventional gauze bandage, PU/F127, PU/F/15 (contained extract), and PU/F/15/10 (contained extract and CGN) prepared with different nanoparticle concentrations of 5 and 10 was 47.1 ± 0.2, 56.4 ± 0.4, 65.14 ± 0.2, and 90.55 ± 0.15%, respectively. Histopathological studies indicated that the wound treated with the extract containing nanofibers showed a considerable inflammation reduction at day 14. Additionally, this group showed more resemblance to normal skin with a thin epidermis presence of normal rete ridges and rejuvenation of skin appendages. Neovascularization and collagen deposition were higher in wounds treated with the extract containing nanofibrous wound dressing compared to the other groups.

Polyurethane/carboxymethylcellulose nanofibers containing Malva sylvestris extract for healing diabetic wounds: Preparation, characterization, in vitro and in vivo studies.

In this study, new polyurethane (PU)-based nanofibers wound dressings containing Malva sylvestris extract were prepared and their effect on diabetic wound healing process was evaluated. Different amounts of carboxymethyl cellulose (CMC) were used to improve the absorption ability of wound exudates. The result showed that the usage of 20% w/w CMC in the polymer blend; and producing of nanofibers with an average diameter of 386.5 nm, led to the gradual release of the herbal compound in 85 h and bead-free morphology. Due to the antibacterial activity of wound dressing and wound healing process, the amount of 15% w/w herbal extract was selected as the optimum. For this sample, the fluid absorption was 412.31%. The extract loaded wound dressing samples showed satisfactory effects on Staphylococcus aureus and Escherichia coli bacteria. In vivo wound-healing and histological performance observations indicated that the use of the herbal extract in wound dressing improved wound healing significantly. On day 14, the average healing rate for gauze bandage, PU/CMC, and different amounts of 5, 10, 15 and 20% w/w extract containing wound dressings was 32.1 ± 0.2%, 51.4 ± 0.4%, 71 ± 0.14%, 87.64 ± 1.02%, 95.05 ± 0.24% and 95.11 ± 0.2%, respectively. Compared to the control groups, treatments with extract loaded wound dressings were effective in lowering acute and chronic inflammations. In diabetic rat wounds, collagen deposition and neovascularization were higher in wounds treated with an herbal extract containing wound dressing compared to the wounds treated with a gauze bandage and PU/CMC treated wounds. It can be suggested that this product may be considered as a good dual anti-inflammatory-antimicrobial wound dressing candidate for improving the diabetic wound healing.

Trachyspermum ammi (L.) Sprague, superb essential oil and its major components on peptic ulcers: in vivo combined in silico studies.

BACKGROUND: Trachyspermum ammi (L.) Sprague is used for treating gastrointestinal disorders. Several studies indicated gastric antiulcer activity of T. ammi extract, yet the effect of its essential oil has not been studied on. OBJECTIVES: The present study evaluates chemical composition of T. ammi essential oil and anti-peptic ulcer effect of the essential oil as well as its three major components in ethanol induced-gastric ulcers in rats. METHODS: Primarily chemical composition of the essential oil was analyzed by gas chromatography-mass spectrometry (GC/MS). Rats received the essential oil (500, 250, 125, 62.5, 31.25 mg/kg), thymol (30, 100 mg/kg), para-cymene (100, 150 mg/kg) and gamma-terpinene (100, 150 mg/kg) using gavage tube along with ethanol 80%. Finally, dissected stomachs were assessed both macroscopically and microscopically to evaluate anti-ulcerative effect of the essential oil and the pure compounds. Moreover, molecular docking was utilized to explore the interactive behavior of the main components with active site residues of H+/K+ ATPase. RESULTS: Analysis of the essential oil indicated that para-cymene (37.18%), gamma-terpinene (35.36%) and thymol (20.51%) are the main components. Administration of different doses of the essential oil noticeably diminished the number of peptic ulcers in a dose-dependent manner. Among the main components, thymol was more potent than para-cymene and gamma-terpinene. Administration of the essential oil (500 mg/kg) and thymol (100 mg/kg) observed maximum inhibition percentage (98.58% and 79.37%, respectively). Molecular docking study provides the evidence of thymol ability to inhibit H+/K+ ATPase. CONCLUSIONS: The findings revealed that T. ammi essential oil can be applied to treat gastric ulcer as a natural agent. Graphical abstract.

Neuroprotective Potential of Curcumin-Loaded Nanostructured Lipid Carrier in an Animal Model of Alzheimer's Disease: Behavioral and Biochemical Evidence.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and is caused by accumulation of amyloid-ß (Aß) peptide and is associated with neurological abnormalities in learning and memory. The protective role of curcumin on nerve cells, along with a potent antioxidant and free radical scavenging activity, has been widely studied. However, its low bioavailability and limited transport ability across the blood-brain barrier are two major drawbacks of its application in the treatment of different neurodegenerative diseases. The present study was designed to improve the effectiveness of curcumin in the treatment of Aß-induced cognitive deficiencies in a rat model of AD by loading it into nanostructured lipid carriers (NLCs). The accumulation rate of curcumin (505.76±38.4 ng/g-1 h) in rat brain, as well as its serum levels, were significantly increased by using curcumin-loaded NLCs. The effective role of NLCs for brain delivery of curcumin was confirmed by reduced oxidative stress parameters (ROS formation, lipid peroxidation, and ADP/ATP ratio) in the hippocampal tissue and improvement of spatial memory. Also, histopathological studies revealed the potential of Cur-NLCs in decreasing the hallmarks of Aß in AD in the animal model. The result of studying the neuroprotective potential of Cur-NLC in both pre-treatment and treatment modes showed that loading curcumin in NLCs is an effective strategy for increasing curcumin delivery to the brain and reducing Aß-induced neurological abnormalities and memory defects and that it can be the basis for further studies in the area of AD prevention and treatment.

Magnetic bio-metal-organic framework nanocomposites decorated with folic acid conjugated chitosan as a promising biocompatible targeted theranostic system for cancer treatment.

In this work, a multifunctional magnetic Bio-Metal-Organic Framework (Fe3O4@Bio-MOF) coated with folic acid-chitosan conjugate (FC) was successfully prepared for tumor-targeted delivery of curcumin (CUR) and 5-fluorouracil (5-FU) simultaneously. Bio-MOF nanocomposite based on CUR as organic linker and zinc as metal ion was prepared by hydrothermal method in the presence of amine-functionalized Fe3O4 magnetic nanoparticles (Fe3O4@NH2 MNPs). 5-FU was loaded in the magnetic Bio-MOF and the obtained nanocarrier was then coated with FC network. The prepared nanocomposite (NC) was fully characterized by high resolution-transmission electron microscope (HR-TEM), field emission scanning electron microscopy (FE-SEM), Dynamic light scattering (DLS), X-ray diffraction analysis (XRD), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), nuclear magnetic resonance (NMR), and UV-vis analyses. In vitro release study showed controlled release of CUR and 5-FU in acidic pH confirming high selectivity and performance of the carrier in cancerous microenvironments. The selective uptake of 5-FU-loaded Fe3O4@Bio-MOF-FC by folate receptor-positive MDA-MB-231 cells was investigated and verified. The ultimate nanocarrier exhibited no significant toxicity, while drug loaded nanocarrier showed selective and higher toxicity against the cancerous cells than normal cells. SDS PAGE was also utilized to determine the protein pattern attached on the surface of the nanocarriers. In vitro and in vivo MRI studies showed negative signal enhancement in tumor confirming the ability of the nanocarrier to be applied as diagnostic agent. Owing to the selective anticancer release and cellular uptake, acceptable blood compatibility as well as suitable T2 MRI contrast performance, the target nanocarrier could be considered as favorable theranostic in breast cancer.

Low, but not high, dose triptolide controls neuroinflammation and improves behavioral deficits in toxic model of multiple sclerosis by dampening of NF-κB activation and acceleration of intrinsic myelin repair.

Cuprizone (Cup) is a copper chelating agent frequently used to study factors that affect oligodendrocytes (OLGs) death and acute demyelination. Triptolide (TP), a nuclear factor-kappaB (NF-κB) blocker, is a major bioactive component of Tripterygium wilfordii Hook f. (TWHf) with various therapeutic activities. In this study, we examined the effects of TP on neuroglia activation, inflammation, apoptosis, demyelination, and behavioral deficits in the Cup-induced toxic model of multiple sclerosis (MS). C57BL/6 J mice were fed with chow containing 0.2% Cup for 6 weeks to induce detectable neuroinflammation and myelin loss. TP was administered intraperitoneally at different doses (125, 250 or 500 µg/kg/day) during the last week of the Cup challenge. Although TP substantially decreased Cup-induced NF-κB extra activation, TNF-α and IL-1 over expression, and gliosis in a dose-dependent manner, only low dose of TP (TP-125) was able to raise the number of OLGs precursor cells (NG-2+/O4+), reduce Bax/Bcl-2 ratio and improve behavioral deficits. In addition, TP-125 decreased NF-κB activation on GFAP+ astrocytes more than MAC-3+ microglial and MOG+ oligodendrocytes which suggested the possibility of specific dampening of NF-κB signaling in reactive astrocytes. Behavioral assessments by open-field and rota-rod tests showed that only TP-125 notably improved motor function and motor coordination compared to the Cup group. These findings highlight the pivotal role of NF-κB signaling in the oligodendrogenesis and lesion reduction in demyelination diseases such as MS.

Effect of the methanolic extracts of different parts of Ferula assa-foetida on naloxone-induced withdrawal behavior in morphine-dependent mice.

OBJECTIVE: Ferula assa-foetida, a native species in Iran, is used for treatment of several diseases particularly for neurological disorders in Iranian Traditional Medicine. The aim of this study is to investigate the effect of methanolic roots, fruits, and aerial parts extracts of Ferula assa-foetida on withdrawal syndrome in morphine-dependent mice. MATERIALS AND METHODS: Aerial parts, roots, and fruits of the plant were separately extracted with 80% MeOH. For induction of dependence, morphine (50, 50 and 75 mg/kg) was injected subcutaneously three times daily (10 am, 1 pm and 4 pm) for three days and a last dose of morphine (50 mg/kg) was administrated on the fourth day. Withdrawal syndrome was induced by injection of naloxone (5 mg/kg, intraperitoneal) 2 hr after the final dose of morphine. Different doses of the extracts were administered i.p. 60 minutes before naloxone injection and withdrawal sign was recorded 2 minutes after naloxone injection for a period of 60 minutes. RESULTS: Pre-treatment of animals with different doses (2.5, 5, 10, 20 mg/kg) of methanolic extract of the aerial parts of F. assa-foetida caused a significant decrease in naloxone-induced behavior. Intraperitoneal administration of different doses (10, 15, 20, 25 mg/kg) of methanolic extract of the fruit significantly reduced the naloxone-induced withdrawal behavior (p<0.001). CONCLUSION: It might be concluded that the extracts of Ferula assa-foetida affect morphine withdrawal syndrome possibly via interference with the neurotransmitters in nervous system.

Melatonin Supplementation May Improve the Outcome of Patients with Hemorrhagic Stroke in the Intensive Care Unit.

OBJECTIVE: Although mechanical ventilation is frequently a life-saving therapy, its use can result in unwanted side effects. It has been well documented that the choice of sedating agent may influence the duration of mechanical ventilation. Melatonin is a sedative and analgesic agent without any respiratory depressant effect which makes it an attractive adjuvant for sedation in the intubated patients. The aim of this study is to evaluate the effect of melatonin on the duration of mechanical ventilation in patients with hemorrhagic stroke. METHODS: Forty adult intubated patients with hemorrhagic stroke, who were admitted to the Intensive Care Unit (ICU) within 24 h of onset, were enrolled in this randomized double-blind study. Subjects in the melatonin group received 30 mg of melatonin every night throughout the nasogastric tube. Length of ICU stay, mortality, and duration of mechanical ventilation were recorded for all patients. FINDINGS: The duration of mechanical ventilation and length of ICU stay were shorter in patients who received melatonin in comparison with the control group, and this difference was statistically significant for the length of ICU stay and marginally significant for the duration of mechanical ventilation. Although not statistically significant, the mortality rate of the control group was 30%, almost double that of the study group (15%). CONCLUSION: Melatonin possesses hypnotic, analgesic, anti-inflammatory, and anti-oxidative properties that distinguish it as an attractive adjuvant in patients under mechanical ventilation. In conclusion, the administration of melatonin may facilitate the weaning process through decreasing the consumption of sedatives with respiratory depressant properties as well as preventing ventilator-associated lung injury.

Protective Effect of a Polyherbal Traditional Formula Consisting of Rosa damascena Mill., Glycyrrhiza glabra L. And Nardostachys jatamansi DC., Against Ethanol-induced Gastric Ulcer.

"VARD" formula consisting of Rosa damascena Mill. (Rosaceae) petals, and rhizomes of Glycyrrhiza glabra L. (Papilionaceae) and Nardostachys jatamansi DC. (Valerianaceae), has been proposed for gastric ulcer in Iranian traditional medicine. We investigated the antiulcer activity of each plant separately and in combination. The biochemical and molecular functions of extracts were also evaluated. Each plant hydroalcoholic extract was standardized via determination of total phenolic and flavonoid contents, also via some phenolic compounds determination and specially glycyrrhizic acid in G. glabra by using HPLC. Rats received orally extracts of the plants (20, 40 and 80 mg/Kg) and "VARD" (45 mg/Kg) 1 h before ethanol administration. Two h after receiving ethanol, animals were sacrificed; the stomach was removed for macroscopic and microscopic assessment. Also heme-oxygenase-1, glutathione, and catalase were measured in the gastric tissue of the rats pretreated by "VARD" and dose of 20 mg/Kg of extracts. Among three extracts, R. damascena and G. glabra contained more total phenolic and flavonoid content respectively. Gallic acid was prominent compound in R. damascena. The extracts of R. damascena, G. glabra, and N. jatamansi significantly decreased ulcer index. ED50 values were 8.2, 31.86 and 25.08 mg/Kg respectively. "VARD" significantly decreased ulcer index compared to 20 mg/Kg of G. glabra (p < 0.0001) and N. jatamansi (p < 0.001). Pretreatment with "VARD" and each plant extracts (20 mg/Kg) increased glutathione, catalse and heme-oxygenase-1 significantly (p < 0.05) in comparison with control group. Our findings indicate that "VARD" partly via antioxidant activity can be considered as an effective antiulcer formula.

PROTECTIVE EFFECT OF IRIS GERMANICA L. IN Β-AMYLOID-INDUCED ANIMAL MODEL OF ALZHEIMER'S DISEASE.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia that is an irretrievable chronic neurodegenerative disease. In the current study, we have examined the therapeutic effects of Iris germanica extract on Amyloid ß (Aß) induced memory impairment. MATERIALS AND METHODS: Wistar rats were divided into five groups of 8 per each. Groups were as followed: control group which were normal rats without induction of AD, Aß group which received Aß (50 ng/side), iris 100 group which received Aß + Iris (100 mg/kg), iris 200 group which received Aß + Iris (200 mg/kg), and iris 400 group which received Aß + Iris (400 mg/kg). AD was established by intrahippocampal injection of 50 ng/µl/side Aß1-42. The day after surgery, animals in treatment groups received different doses of the aqueous extract of Iris by gavage for 30 days. Morris water maze test (MWM) was performed to assess the effects of I. germanica on learning and memory of rats with Aß induced AD. RESULTS: Data from MWM tests, including escape latency and traveled distance, demonstrated that I. germanica extract could markedly improve spatial memory in comparison to control. Moreover, the plant had a significantly better effect on the performance of AD rats in the probe test. CONCLUSION: I. germanica extract can successfully reverse spatial learning dysfunction in an experimental model of AD. Further neuro psyco-pharmacological studies are mandatory to reveal the mechanism of action of this natural remedy in the management of AD symptoms.

Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis.

CONTEXT: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions. OBJECTIVE: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated. MATERIAL AND METHODS: C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p.) from the first day of cup diet. Oligodendrocytes apoptosis [TUNEL assay and myelin oligodendrocyte glycoprotein (MOG+)/caspase-3+ cells), gliosis (H&E staining, glial fibrillary acidic protein (GFAP+) and macrophage-3 (Mac-3+) cells) and inflammatory markers (interleukin 17 (IL-17), interleukin 11 (IL-11) and stromal cell-derived factor 1 α (SDF-1α) or CXCL12] during cup intoxication were examined. RESULTS: High dose of EA (EA-80) increased mature oligodendrocytes population (MOG+ cells, p < 0.001), and decreased apoptosis (p < 0.05) compared with the cup mice. Treatment with both EA doses did not show any considerable effects on the expression of CXCL12, but significantly down-regulated the expression of IL-17 and up-regulated the expression of IL-11 in mRNA levels compared with the cup mice. Only treatment with EA-80 significantly decreased the population of active macrophage (MAC-3+ cells, p < 0.001) but not reactive astrocytes (GFAP+ cells) compared with the cup mice. DISCUSSION AND CONCLUSION: In this model, EA-80 effectively reduces lesions via reduction of neuroinflammation and toxic effects of cup on mature OLGs. EA is a suitable therapeutic agent for moderate brain damage in neurodegenerative diseases such as multiple sclerosis.

Antinociceptive effect of extracts of Marrubium astracanicum Jacq. aerial parts.

OBJECTIVE: The genus Marrubium is used for treatment of joint pain, gout, stomach-ache and colic in Iranian Traditional Medicine. Marrubium astracanicum Jacq. (M. astracanicum) is a native species in the flora of Iran. The aim of this study was to evaluate the antinociceptive properties of various extracts of aerial parts of M. astracanicum. MATERIALS AND METHODS: Antinociceptive activities of total hydroalcoholic extract (THE) and its n-hexane (non-polar) and residual partition (polar) fractions were analyzed using formalin test in mice. Morphine (5 mg/kg) and normal saline were used as positive and negative controls, respectively. RESULTS: Intraperitoneal administration of THE (50, 100 and 200 mg/kg), non-polar fraction (200 mg/kg) and polar fraction (100 and 200 mg/kg), 30 min before formalin injection, caused significant analgesic activity in acute phase (0-5 min after formalin injection) of formalin test (p<0.05 as compared to control and p>0.05 in comparison with morphine). In chronic phase (15-60 min after formalin injection), non-polar and polar fractions (50, 100 and 200 mg/kg) showed significant analgesic activity (p<0.001 as compared to control and p>0.05 in comparison with morphine). CONCLUSION: Different extracts of M. astracanicum demonstrated antinociceptive activity that support the traditional usage of Marrubium genus for the treatment of arthritis, gout and other inflammatory diseases.

Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function.

Oxidative stress and mitochondrial dysfunction play indispensable role in memory and learning impairment. Growing evidences have shed light on anti-oxidative role for melatonin in memory deficit. We have previously reported that inhibition of protein kinase A by H-89 can induce memory impairment. Here, we investigated the effect of melatonin on H-89 induced spatial memory deficit and pursued their interactive consequences on oxidative stress and mitochondrial function in Morris Water Maze model. Rats received melatonin (50 and 100µg/kg/side) and H-89(10µM) intra-hippocampally 30min before each day of training. Animals were trained for 4 consecutive days, each containing one block from four trials. Oxidative stress indices, including thiobarbituric acid (TBARS), reactive oxygen species (ROS), thiol groups, and ferric reducing antioxidant power (FRAP) were assessed using spectrophotometer. Mitochondrial function was evaluated through measuring ROS production, mitochondrial membrane potential (MMP), swelling, outer membrane damage, and cytochrome c release. As expected from our previous report, H-89 remarkably impaired memory by increasing the escape latency and traveled distance. Intriguingly, H-89 significantly augmented TBARS and ROS levels, caused mitochondrial ROS production, swelling, outer membrane damage, and cytochrome c release. Moreover, H-89 lowered thiol, FRAP, and MMP values. Intriguingly, melatonin pre-treatment not only effectively hampered H-89-mediated spatial memory deficit at both doses, but also reversed the H-89 effects on mitochondrial and biochemical indices upon higher dose. Collectively, these findings highlight a protective role for melatonin against H-89-induced memory impairment and indicate that melatonin may play a therapeutic role in the treatment of oxidative- related neurodegenerative disorders.

Recent Updates in Imperative Natural Compounds for Healthy Brain and Nerve Function: A Systematic Review of Implications for Multiple Sclerosis.

BACKGROUND: The evolution of the Green movement in western society has changed attitudes in the general population who now perceive natural compounds as being inherently harmless and more desirable than artificial chemical products. OBJECTIVE: Considering the growing interest towards introducing naturally emerged medicines, the purpose of this review was to overview the ongoing research into prevention and treatment of multiple sclerosis (MS) lesions. METHOD: This review was carried out by searching bibliographic databases such as PubMed and Scopus for studies reported between 1st January 2008 to 30th January 2016 on MS patients or animal models of MS, investigating the beneficial effects of natural compounds in MS treatment. In this updated systematic review, the search terms were "multiple sclerosis" or "neurodegeneration" and ("natural compounds" or "medicinal plants", "traditional medicine" or "native medicine"). RESULTS: Studies with vitamins (A, B12, D, H), minerals (selenium and lithium), n-3 PUFAs, lipoic acid, statins, resveratrol, marijuana, EGCG and some probiotics have shown significant helpful effects in MS by preventing or delaying the onset of disease. Other natural compounds such as xanthines, anthocyanins, glucosinolates, isoflavones, organosulfurs, steroid glycosides, and alkaloids have also shown protective effects in the treatment of MS in animal models. Adverse effects were also reported in some of the experiments. CONCLUSION: Further studies with a focus on the molecular mechanisms of the protective natural compounds are needed to decrease possible side effects and to develop new medicines for MS. Apigenin, chrysin, baicalein, cyanidin, flavone glycoside, daidzein, coumestrol, sulforaphane, bee venom and huperzine A are the candidates for more prospective investigations.

Protective effect of essential oil of Pistacia atlantica Desf. on peptic ulcer: role of α-pinene.

OBJECTIVE: To evaluate the efficacy of Pistacia atlantica Desf. oleoresin essential oil on peptic ulcer (PU) and its antibacterial effect on metronidazole-resistant Helicobacter pylori, as well as chemical composition of the essential oil. METHODS: The essential oil was standardized using gas chromatography mass spectrometry (GC/MS) analysis. Acute toxicity of the essential oil was assessed in animal model. In vitro anti-Helicobacter pylori activity was performed through disc diffusion and minimum inhibitory concentration method. For gastroprotective assay, rats received Pistacia atlantica Desf. essential oil (25, 50 and 100 mg/kg orally) 1 h before induction of ulcer by ethanol. Macroscopic (ulcer index and protection rate) and microscopic examination were performed. RESULTS: The GC/MS analysis of the essential oil led to the identification of twenty constituents and α-pinene is predominant constituent. The essential oil was safe up to 2000 mg/kg. All Helicobacter pylori strains were susceptible to the essential oil and the MIC ranged from 275 to 1100 µg/mL. The ulcer index for treated groups was significantly reduced compared to control (P < 0.001) with EC(50) value of 12.32 mg/kg. In microscopic examination, Pistacia atlantica attenuated destruction and necrosis of gastric tissue. CONCLUSION: Current study exhibited protective effect of standardized Pistacia atlantica essential oil against ethanol-induced gastric ulcer and its antibacterial activity on Helicobacter pylori. α-pinene might be the responsible agent.

Protective effect of vitamin C, vitamin B12 and omega-3 on lead-induced memory impairment in rat.

Lead belongs to the heavy metal group and is considered as an environmental contaminant. Acute or chronic contact to lead can change the physiological function of human organs. One of the most important disorders following the lead exposure is neurotoxicity. Lead neurotoxicity consists of the neurobehavioral disturbances like cognitive impairment. The aim of the current study is to evaluate the possible protective effect of vitamin C (Vit C), vitamin B12 (Vit B12), omega 3 (ω-3), or their combination on the lead-induced memory disorder. Adult wistar rats were orally administered Vit C (120 mg/kg/day) or Vit B12 (1 mg/kg/day) or ω-3 (1000 mg/kg/day) or their combination for 3 weeks in groups of 7 animals each. Then lead acetate (15 mg/kg/day) was injected intraperitoneally for one week to all pretreated animals. The control group received normal saline as a vehicle while the positive control for cognitive impairment received just lead acetate. At the end of treatments animal memories were evaluated in Object Recognition Task. The results showed, although 15 mg/kg lead acetate significantly declines the memory-evaluating parameters, pretreatment with Vit C, Vit B12, ω-3, or their combination considerably inverted the lead induced reduction in discrimination (d2) index (P < 0.001) and recognition (R) index (P < 0.001, P < 0.05, P < 0.05, and P < 0.001, respectively). Our findings indicate while lead acetate impairs spatial memory in rat, administration of Vit C, Vit B12, ω-3, or their combination prior to the lead exposure inhibits the lead induced cognitive loss. There was no remarkable difference in this effect between the used supplements.

Preparation and Bioavailability Analysis of Ferrous Bis Alanine Chelate as a New Micronutrient for Treatment of Iron Deficiency Anemia.

Purpose: One of the most nutritional disorders around the world is iron deficiency. A novel iron compound was synthesized by chelating ferrous ions with alanine for prevention and treatment of iron deficiency anemia. Methods: The newly synthesized compound was characterized both qualitatively and quantitatively by Fourier Transform Infrared (FT-IR) spectroscopy. The bioavailability of newly synthesized iron micronutrient was evaluated in four groups of Wistar rats. The group I was a negative control group and the other three groups received three different iron formulations. After 14 days, the blood samples were taken and analyzed accordingly. Results: Calculations showed that more than 91.8% of iron was incorporated in the chelate formulation. In vivo studies showed that serum iron, total iron binding capacity and hemoglobin concentrations were significantly increased in group IV, which received ferrous bis alanine chelate compared with the negative control group (p<0.05) and also group II, which received ferrous sulfate.7H2O (p<0.05). It indicates that the new formulation considerably improves the blood iron status compared with the conventional iron compounds. There were no significant differences (p<0.05) in the serum iron between group IV and group III, which received ferrous bis glycine. Conclusion: The results showed better bioavailability of ferrous bis alanine as a new micronutrient for treatment of iron deficiency anemia in comparison with ferrous sulfate. Ferrous bis alanine could be considered as a suitable supplement for prevention and treatment of iron deficiency anemia.