Sericin Improves Memory Impairment Via Activation of the PKA-CREB-BDNF Signaling Pathway and Suppression of Oxidative Stress in Ovariectomized Mice.

Menopause results in estrogen hormone deficiency which causes changes in brain morphology and cognitive impairments. The risk of breast and ovarian cancer increases with estrogen therapy. Thus, finding a substitute treatment option for women in menopause is necessary. In the current study, the impact of chronic sericin treatment (200 mg/kg/day for 6 weeks, gavage) on memory process, oxidative stress markers, synaptic neurotransmission, and acetylcholinesterase (AChE) activity in the hippocampus (HIP) of ovariectomized (OVX) mice was examined and compared to the effects of 17ß-estradiol (Es; 20 µg/kg, s.c.). The results demonstrated that sericin and Es administration improved spatial and recognition memory of the OVX animals in the both Lashley III maze and novel object recognition tests. Moreover, sericin-treated OVX mice showed decreased ROS levels, increased endogenous antioxidant defense capacity, and decreased AChE activity in the HIP. Additionally, sericin and Es therapy up-regulated pre-and-post-synaptic protein markers and increased BDNF, CREB, and protein kinase A (PKA) protein expressions in the HIP of OVX mice. Overall, the activation of the PKA-CREB-BDNF signaling pathway by sericin can provide protection against OVX-induced cognitive dysfunction, making it a potential alternative for managing cognitive deficits in postmenopausal women.

Photobiomodulation combination therapy as a new insight in neurological disorders: a comprehensive systematic review.

Preclinical and clinical studies have indicated that combining photobiomodulation (PBM) therapy with other therapeutic approaches may influence the treatment process in a variety of disorders. The purpose of this systematic review was to determine whether PBM-combined therapy provides additional benefits over monotherapies in neurologic and neuropsychiatric disorders. In addition, the review describes the most commonly used methods and PBM parameters in these conjunctional approaches.To accomplish this, a systematic search was conducted in Google Scholar, PubMed, and Scopus databases through January 2024. 95 potentially eligible articles on PBM-combined treatment strategies for neurological and neuropsychological disorders were identified, including 29 preclinical studies and 66 clinical trials.According to the findings, seven major categories of studies were identified based on disease type: neuropsychiatric diseases, neurodegenerative diseases, ischemia, nerve injury, pain, paresis, and neuropathy. These studies looked at the effects of laser therapy in combination with other therapies like pharmacotherapies, physical therapies, exercises, stem cells, and experimental materials on neurological disorders in both animal models and humans. The findings suggested that most combination therapies could produce synergistic effects, leading to better outcomes for treating neurologic and psychiatric disorders and relieving symptoms.These findings indicate that the combination of PBM may be a useful adjunct to conventional and experimental treatments for a variety of neurological and psychological disorders.

Synergistic effects of combined therapy with cerebrolysin and enriched environment on anxiety-like behavior and spatial cognitive deficits in posttraumatic stress disorder-like mouse model.

Posttraumatic stress disorder (PTSD) is a serious neuropsychiatric disorder that occurs after exposure to stressful, fearful, or troubling events. Cerebrolysin (CBL), consists of low molecular weights neurotrophic factors and amino acids obtained from purified porcine brain proteins. This study aimed to evaluate the possible therapeutic effects of enriched environment (EE) and CBL alone or combined for reducing anxiety and cognitive deficits in PTSD-like mouse models. For this purpose, inescapable electric foot shocks were delivered to Balb/c mice for two consecutive days. Then mice were treated with CBL (2.5 mL/kg) and/or were kept in EE (2 h per day) or received their combination for 14 consecutive days. The hole-board test and Lashley III paradigm were used to assess anxiety and spatial learning and memory, respectively. Changes in the serum corticosterone level and expression of synaptic elements, including; growth-associated protein 43, post-synaptic density 95, and synaptophysin were assessed in the hippocampus. This model caused anxiety and spatial memory impairment associated with increased serum corticosterone levels and decreased synaptic elements. Nevertheless, CBL and/or combination treatment could reverse behavioral and molecular alterations. Our findings indicated that CBL, separately or in combination with EE, is effective in reducing anxiety and spatial memory impairment in PTSD-like mice.

Sericin improves memory and sociability impairments evoked by transient global cerebral ischemia through suppression of hippocampal oxidative stress, inflammation, and apoptosis.

Sericin (Ser) is a natural neuroactive macromolecule with diverse pharmacological properties, and our previous findings have shown its neuroprotective potentials. This study aimed to investigate the therapeutic potential of Ser on cognitive dysfunction induced by transient global cerebral ischemia/reperfusion (tGI/R) and its mechanism of action. The tGI/R was induced in BALB/c mice by bilateral occlusion of the common carotid arteries for two 5 min followed by a 10-min reperfusion period. After 24 h, mice were treated with normal saline or different doses of Ser (100, 200, and 300 mg/kg) for 10 days. Cognitive performances were assessed using the Barnes maze and social interaction tasks. Oxidative stress markers including superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and malondialdehyde (MDA) as well as pro-inflammatory cytokines (interleukin (IL)-6 and tumor necrosis factor-alpha) and anti-inflammatory cytokine (IL-10) were assessed in the hippocampus. Markers of apoptosis (pro- and cleaved caspase-9 and 3, Bax, and Bcl-2) were assessed by Western blotting. Besides, transferase-mediated dUTP nick end-labeling assay was used to detect apoptotic cell death. We show here that Ser administration improved tGI/R-induced cognitive deficits, enhanced the activity of SOD and GPx, increased TAC levels, while reduced MDA levels. Notably, Ser decreased neuronal apoptotic cell death in the hippocampal dentate gyrus (DG) region, accompanied by suppression of neuroinflammation, downregulation of pro-apoptotic proteins (caspase-9, caspases-3, and Bax), and upregulation of anti-apoptotic protein, Bcl-2. Taken together, Ser administration protected hippocampal neurons from apoptotic cell death by impeding oxidative stress and inflammatory responses and, in turn, improved cognitive function in the tGI/R mice.

Therapeutic potential of neurotrophic factors in Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia among the elderly population. AD is accompanied with the dysregulation of specific neurotrophic factors (NTFs) and their receptors, which plays a critical role in neuronal degeneration. NTFs are small proteins with therapeutic potential for human neurodegenerative diseases. These growth factors are categorized into four families: neurotrophins, neurokines, the glial cell line-derived NTF family of ligands, and the newly discovered cerebral dopamine NTF/mesencephalic astrocyte-derived NTF family. NTFs are capable of preventing cell death in degenerative conditions and can increase the neuronal growth and function in these disorders. Nevertheless, the adverse side effects of NTFs delivery and poor diffusion of these factors in the brain restrict the efficacy of NTFs therapy in clinical situations. MATERIALS AND METHODS: In this review, we focus on the current advances in the use of NTFs to treat AD and summarize previous experimental and clinical studies for supporting the protective and therapeutic effects of these factors. CONCLUSION: Based on reports, NTFs are considered as new and promising candidates for treating AD and AD-associated cognitive impairment.

Clinical application of stem cell therapy in neurogenic bladder: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: This review aims to investigate the effect of stem cell (SC) therapy on the management of neurogenic bladder (NGB) in four neurological diseases, including spinal cord injury (SCI), Parkinson's disease (PD), multiple sclerosis (MS), and stroke, in the clinical setting. METHODS: An electronic database search was conducted in the Cochrane Library, EMBASE, Proquest, Clinicaltrial.gov , WHO, Google Scholar, MEDLINE via PubMed, Ovid, Web of Science, Scopus, ongoing trial registers, and conference proceedings in June 2019 and updated by hand searching on 1 February 2021. All randomized controlled trials (RCTs), quasi RCTs, phase I/II clinical trials, case-control, retrospective cohorts, and comprehensive case series that evaluated the regenerative potential of SCs on the management of NGB were included. Cochrane appraisal risk of bias checklist and the standardized critical appraisal instrument from the JBI Meta-Analysis of Statistics, Assessment, and Review Instrument (JBI-MAStARI) were used to appraise the studies. RESULTS: Twenty-six studies among 1282 relevant publications met our inclusion criteria. Only SC therapy was applied for SCI or MS patients. Phase I/II clinical trials (without control arm) were the most conducted studies, and only four were RCTs. Four studies with 153 participants were included in the meta-analysis. The main route of transplantation was via lumbar puncture. There were no serious adverse events. Only nine studies in SCI and one in MS have used urodynamics, and the others have reported improvement based on patient satisfaction. SC therapy did not significantly improve residual urine volume, detrusor pressure, and maximum bladder capacity. Also, the quality of these publications was low or unclear. CONCLUSION: Although most clinical trials provide evidence of the safety and effectiveness of MSCs on the management of NGB, the meta-analysis results did not show a significant improvement; however, the interpretation of study results is difficult because of the lack of placebo controls.

Synergistic effects of combined therapy with transcranial photobiomodulation and enriched environment on depressive- and anxiety-like behaviors in a mice model of noise stress.

The development of anxiety and depression due to chronic exposure to noise stress has remained as an unsolved health problem so far. Despite the studies suggesting the neuroenhancement effects of transcranial photobiomodulation (tPBM) and housing in an enriched environment (EE), the combined effects of these treatments have not been elucidated yet. Also, there is no available data on the relationship between the application of tPBM and hippocampal brain-derived neurotrophic factor (BDNF) expression in animal models of stress. The present study aims to investigate the application of the tPBM and EE (alone or in combination) on depressive- and anxiety-like behaviors in a mice model of noise stress. Mice were divided into five groups: control, noise, noise + EE, noise + tPBM, and noise + EE + tPBM. Except for the control group, other groups were subjected to 110 dB SPL white noise for 4 h/day for 14 consecutive days and received their respective treatments. Forced Swimming Test (FST) was used to evaluate depressive-like behaviors. Elevated Plus Maze (EPM) and Open Field Test (OFT) were used to evaluate anxiety-like behaviors. BDNF, tyrosine receptor kinase B (TrkB), and cAMP response element-binding (CREB) protein levels in the hippocampus were determined by the Western blot method, and also serum corticosterone levels were assessed using an ELISA kit. Exposure to noise stress significantly elevated serum corticosterone level; downregulated hippocampal BDNF, TrkB, and CREB protein expressions; and resulted in depressive- and anxiety-like behaviors. While, the application of tPBM (810 nm wavelength, 8 J/cm2 fluence, 10 Hz pulsed wave mode), housing in EE, and their combination lowered corticosterone levels, upregulated the BDNF/TrkB/CREB signaling pathway in the hippocampus, and improved behavioral outcomes in noise stress subjected mice. Our finding revealed the improving effects of tPBM and EE on depressive and anxiety-like behaviors induced by noise stress, possibly by augmenting the BDNF/TrkB/CREB signaling pathway.

Effect of transcranial near-infrared photobiomodulation on cognitive outcomes in D-galactose/AlCl3 induced brain aging in BALB/c mice.

Brain photobiomodulation (PBM) therapy (PBMT) modulates various biological and cognitive processes in senescence rodent models. This study was designed to investigate the effects of transcranial near-infrared (NIR) laser treatment on D-galactose (D-gal)/aluminum chloride (AlCl3) induced inflammation, synaptic dysfunction, and cognitive impairment in mice. The aged mouse model was induced by subcutaneously injecting D-gal (60 mg/kg/day) followed by intragastrically administering AlCl3 (200 mg/kg/day) for 2 months. NIR PBM (810 nm laser, 32, 16, and 8 J/cm2) was administered transcranially every other day (3 days/week) for 2 months. Social, contextual, and spatial memories were assessed by social interaction test, passive avoidance test, and Lashley III maze, respectively. Then, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and synaptic markers including growth-associated protein 43 (GAP-43), post-synaptic density-95 (PSD-95), and synaptophysin (SYN) levels were measured in the hippocampus using western blot method. Behavioral results revealed that NIR PBM at fluencies of 16 and 8 J/cm2 could reduce D-gal/AlCl3 impaired social and spatial memories. Treatment with NIR attenuated neuroinflammation through down-regulation of TNF-α and IL-6. Additionally, NIR significantly inhibited the down-regulation of GAP-43 and SYN. The results indicate that transcranial PBM at the fluencies 16 and 8 J/cm2 effectively prevents cognitive impairment in mice model of aging by inhibiting the production of the inflammatory cytokines and enhancing synaptic markers.

The effect of fecal microbiota transplantation on stroke outcomes: A systematic review.

BACKGROUND AND PURPOSE: Fecal microbiota transplantation (FMT) is a novel microbiota-based therapeutic method that transfers stool from donor into a recipient and its application is under investigating for neurological disorders such as stroke. In this systematic review, we assessed the effect of FMT in progression and treatment of stroke and recovery of post-stroke complications. METHODS: Preliminary studies were searched in MEDLINE via PubMed, Scopus, COCHRANE library and Google Scholar, databases up to February 2022. The search strategy was restricted to articles about FMT in stroke. The initial search yielded 4570 articles, of which 19 publications were included in our systematic review. RESULTS: Based on outcomes transferring microbiome from healthy or ischemic donor to other ischemic recipient can affect brain infarct volume and survival rate, neurological and behavioral outcomes, and inflammatory pathways. CONCLUSIONS: Our systematic review on preclinical studies showed that manipulating gut microbiota via FMT can be a possible therapeutic approach for treatment of stroke and recovery of post-stroke complications.

Intranasal administration of mitochondria alleviated cognitive impairments and mitochondrial dysfunction in the photothrombotic model of mPFC stroke in mice.

OBJECTIVES: Dysfunction in mitochondrial activity may have profound role in ischemic stroke-induced neuronal death, hence maintaining the mitochondrial function seems to be valuable for neuronal viability and neurological improvement. METHODS: C57BL/6J mice were allocated into sham and stroke groups. Mice in the stroke groups underwent photothrombosis-induced stroke in the medial prefrontal cortex (mPFC) and were divided into the following subgroups; RB, Mito 85, Mito 170, and Mito 340, and received their respective treatments via intra-nasal route every other day (3 days per week) for one week. A battery of behavioral tests including social interaction, passive avoidance, and the Lashley III maze was used to investigate social, contextual, and spatial memories. Moreover, changes in mitochondrial function, including reactive oxygen species (ROS) and ATP levels, and mitochondrial membrane potential, were assessed in mPFC. The expression of growth-associated protein 43 (GAP-43), post-synaptic density-95 (PSD-95), and synaptophysin (SYP) was detected by western blotting. RESULTS: Behavioral results revealed that mitotherapy alleviated ischemia-induced memory impairment. Also, transplantation of exogenous mitochondria lowered ROS, restored ATP generation, and improved mitochondrial membrane potential. Induction of ischemia decreased the levels of synaptic markers in mPFC while exogenous mitochondria (170 and 340µg) significantly upregulated the expression of GAP-43 and PSD-95 after ischemic stroke. CONCLUSION: Our research highlighted the importance of mitotherapy in regulating synaptic markers expression and mitochondria function, which could represent a potential strategy for improving cognitive and memory deficits following stroke.

Cerebrolysin® and Environmental Enrichment, Alone or in Combination, Ameliorate Anxiety- and Depressive-Like Behaviors in a Post-Ischemic Depression Model in Mice.

OBJECTIVES: This study examined the beneficial effects of cerebrolysin (CBL) and enriched environment (EE), alone or in combination, on the neurobehavioral and molecular changes in the post-ischemic depression (PID) model in mice. MATERIALS AND METHODS: PID was induced in male Balb/c mice (25-30 g) by combining the transient bilateral common carotid artery occlusion (bCCAO), twice for 5 min at the interval of 10 min, with spatial restraint stress (2 h/day) for 2 weeks, started 48 h following the establishment of bCCAO model. Animals in the treatment groups received CBL (2.5 ml/kg) and/or were housed in EE (2 h/day) for two weeks. Anxiety- and depressive-like behaviors and sociability were evaluated the day after the last experiment. Changes in the serum corticosterone level, the hippocampal oxidative stress status, inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and phosphorylated cAMP response element-binding protein (p-CREB)/CREB ratio were also detected. RESULTS: PID model induced anxiety- and depressive-like behaviors and impaired social behavior. These behavioral changes were accompanied by increased serum corticosterone level, increased lipid peroxidation, decreased antioxidant enzyme activities, reduced BDNF levels and p-CREB/CREB ratio, and increased protein levels of NF-κB and Iba-1 in the hippocampus. However, treatment with CBL and/or EE reversed behavioral and molecular changes induced by PID. CONCLUSION: Our findings imply that the model mimics many manifestations of human PID, and CBL and EE treatments, separately or in combination, are beneficial in reducing anxiety- and- depressive-like behaviors in this model.

Sericin Alleviates Thermal Stress Induced Anxiety-Like Behavior and Cognitive Impairment Through Regulation of Oxidative Stress, Apoptosis, and Heat-Shock Protein-70 in the Hippocampus.

Exposure to heat stress (HS) has adverse effects on brain function, leading to anxiety-like behavior and memory impairment. Sericin is a silk derived protein with various neurobiological activities. The present study has investigated the effects of sericin on anxiety and cognitive impairments, in HS-received mice. The adult male mice were exposed to HS (43 ºC, 15 min once a day for 14 days) and simultaneously treated with 100, 150, and 200 mg/kg/day of sericin through oral gavage. Elevated plus-maze and Lashley III Maze tests were used to evaluate anxiety and learning and memory, respectively. The hippocampal BAX, BCL-2, caspase3, caspase9 and heat-shock protein-70 (HSP-70) were evaluated by western blotting and oxidative stress markers including malondialdehyde (MDA), total antioxidant capacity (TAC), super oxide dismutase (SOD) as well as glutathione peroxidase (GPx) were evaluated by spectroscopy method. The serum was collected for the analysis of the corticosterone levels. Treatment with sericin in higher doses reversed anxiety-like behavior and cognitive deficit induced by HS. Moreover, heat exposure increased serum corticosterone, hippocampal MDA, apoptotic proteins and HSP-70 levels. Sericin administration decreased serum corticosterone and enhanced hippocampal antioxidant defense and attenuated apoptosis and HSP-70 levels. The results show that the protective effects of sericin against HS-mediated cognitive dysfunction and anxiety-like behavior is possibly through suppressing HSP-70, oxidative stress and apoptosis.

Sericin modulates learning and memory behaviors by tuning of antioxidant, inflammatory, and apoptotic markers in the hippocampus of aged mice.

Sericin is a protein derived from silkworm cocoons and identified as an anti-aging agent. This study aimed to examine the effects of sericin administration on episodic and avoidance memories, social interaction behavior, and molecular mechanisms including oxidative stress, inflammation, and apoptosis in the hippocampus of aged mice. Sericin was administered at 250 mg/kg/day (oral gavage) to 2-year-old BALB/c mice for a duration of 21 consecutive days. Lashley III Maze and Shuttle-Box tests were performed to assess episodic and avoidance memories, respectively. Subjects also underwent social interaction test to reveal any changes in their social behavior. Besides, markers of oxidative stress (TAC, SOD, GPx, and MDA) and neuroinflammation mediators (TNF-α, IL-1ß, and IL-10) were measured in the hippocampus. The extent of apoptosis in the hippocampal tissue was further determined by TUNEL assay and histological assessment. The obtained results suggest that sericin promotes episodic and avoidance memories and social behaviors in aged mice. As of the molecular assay outcomes, it was noted that sericin regulates hippocampal inflammation by inhibiting the pro-inflammatory cytokines, TNF-α and IL-1ß, and by increasing the anti-inflammatory factor IL-10. Moreover, sericin suppressed oxidative stress by enhancing antioxidant markers (TAC, SOD, and GPx) and inhibiting MDA. It was also identified that sericin can substantially suppress the apoptosis in the hippocampal tissue. Overall, sericin modulates memory and sociability behavior by tuning hippocampal antioxidant, inflammatory, and apoptotic markers in the aged mice.

Heat stress aggravates oxidative stress, apoptosis, and endoplasmic reticulum stress in the cerebellum of male C57 mice.

BACKGROUND: The current study was set to assess the effect of heat stress exposure on oxidative stress, apoptosis, and endoplasmic reticulum stress markers in the cerebellum of male mice. METHODS: Fifty male C57BL/6 mice were assigned to five groups of (I) control, (II) heat stress (HS)7, (III) HS14, (IV) HS21, and (V) HS42 groups. Animals in the control group were not exposed to HS. Mice in the II-V groups were exposed to HS once a day over 7, 14, 21, and 42 days, respectively. Cerebellar reactive oxygen species (ROS) levels, expression of heat shock protein (HSP)70 and caspase 3 as well as endoplasmic reticulum stress-related proteins (PERK, p-PERK, CHOP, and Full-length ATF-6) expression were determined on the 7th, 14th, 21st, and 42nd days. RESULTS: ROS levels and HSP70 expression increased following HS on the 14th, 21st, and 42nd days and the 7th, and 14th days with a peak level of expression on the 14th day following HS. HSP70 levels decreased afterward on the 21st and 42nd days compared with the control group. Besides, exposure to HS for 14, 21, and 42 days resulted in a significant increase in the CHOP and p-PERK levels in the cerebellum compared with the control group. Heat exposure also increased protein expression of cleaved caspase 3 and active ATF-6/Full-length ATF-6 on the 21st and 42nd days in the cerebellum compared with the control animals. CONCLUSION: These findings indicated that chronic HS augmented oxidative stress, endoplasmic reticulum stress, and apoptosis pathways in the cerebellum of mice.

Harmful effects of high amounts of glucose on the immune system: An updated review.

Release and storage of energy can be regulated by the metabolic parameter dependent on the central nervous system. Macrophages are one of the most professional antigen-presenting cells that are formed by the accumulation of dead or damaged cells or in response to the infection, which has the main function of phagocytosis, secretion of cytokines, and presenting antigen to T cells. A proper immune response is needed for the production of effector cytokines along with comprehensive and rapid cell proliferation and growth. Activation of the immune system and immune cells is needed to increase glucose metabolism. When the immune system responds to pathogens, chemokines inform immune cells such as macrophages and T cells to travel to the infected area. Although glucose is vital for the proper function of immune cells and their proliferation, a high amount of glucose may lead to impaired function of the immune system and pathological conditions. However, a suitable amount of glucose is indispensable for the immune system, but its elevated amount leads to excessive proinflammatory cytokines production. In this study, we focused on the master regulatory role of glucose on the immune system.

A closer look at the role of insulin for the regulation of male reproductive function.

While insulin demonstrates to have a considerable influence on the reproductive system, there are various unanswered questions regarding its precise sites, mechanisms of action, and roles for the developing and functioning of the adult male reproductive system. Apart from its effects on glucose level, insulin has an important role in the reproductive system directly by binding on insulin and IGF receptors in the brain and testis. To date, however, the effect of insulin or its alterations on blood-testis-barrier, as an important regulator of normal spermatogenesis and fertility, has not yet been studied. This review aimed to focus on the experimental and clinical studies to describe mechanisms by which insulin affects the hypothalamic-pituitary-gonadal (HPG) axis, testicular cells, spermatozoa, and sexual behavior. Moreover, we discussed the mechanism and impact of insulin changes in type 1 (insulin deficiency along with persisted or even increased sensitivity) and 2 (insulin resistance along with increased insulin level at the early stages of disease) diabetes and obesity on the male reproductive tract.

miR-143 acts as an inhibitor of migration and proliferation as well as an inducer of apoptosis in melanoma cancer cells in vitro.

Melanoma is a serious form of skin cancers begins in the melanocyte. Micro-RNAs are small noncoding RNA with 19 to 25 nucleotides in length involves in the regulation of a wide range of biological processes. MicroRNAs are affected by an aberrant epigenetic alteration in the tumors that may lead to their dysregulation and formation of cancer. Recently, dysregulation of numerous microRNAs has been reported in different types of cancer. The present study focused on the role of miR-143 in carcinogenesis of melanoma cancer. Here, we evaluated the expression level of miR-143 in three melanoma cell lines in comparison with the normal human epidermal melanocyte cell line. Then, miR-143 gene plasmid transfected into the WM115 cell line, for having the lowest expression of miR-143. In addition, the effect of miR-143 transfection on mRNA and protein levels of metastasis-related genes was performed along with MTT assay, wound healing assay, and flow cytometry. The results showed that mRNA and protein expression levels of metastasis-related genes including MMP-9, E-cadherin, Vimentin, and CXCR4 have been reduced following transfection of miR-143. Moreover, the results of the scratch test showed that miR-143 re-expression inhibited cell migration. Also, the role of miR-143 in the induction of apoptosis and inhibition of proliferation by flow cytometry and MTT was confirmed. As a result, the present study showed that miR-143 was involved in metastatic and apoptotic pathways, suggesting that miR-143 acts as a tumor-suppressor microRNA in melanoma cancer.

Melissa officinalis L. hydro-alcoholic extract inhibits anxiety and depression through prevention of central oxidative stress and apoptosis.

NEW FINDINGS: What is the central question of this study? How does an extract of Melissa officinalis L. ameliorate anxiety- and depressive-like behaviour of mice? What is the main finding and its importance? An extract of Melissa officinalis L. possessed anxiolytic and anti-depressant effects, which could mainly be mediated through its antioxidant and anti-apoptotic properties. ABSTRACT: This study evaluated the effects of a hydro-alcoholic extract of Melissa officinalis (HAEMO) on anxiety- and depressive-like behaviours, oxidative stress and apoptosis markers in restraint stress-exposed mice. In order to induce a depression-like model, mice were subjected to restraint stress (3 h day-1 for 14 days) and received normal saline or HAEMO (50, 75 and 150 mg kg-1  day-1 ) for 14 days. The administered doses of HAEMO were designated based on the concentration of one of the main phenolic compounds present in the extract, rosmarinic acid (2.55 mg kg-1 at lowest dose); other phytochemical analyses including assays for antioxidant activity, total phenols and flavonoids were also carried out. The behavioural changes in an open field task, elevated plus maze, tail suspension and forced swimming tests were evaluated. Also, malondialdehyde (MDA) levels and enzyme activities of superoxide dismutase and glutathione peroxidase, and total antioxidant capacity were assessed in the prefrontal cortex and hippocampus. Moreover, levels of Bcl-2, Bax and caspase 3 in the brain as well as serum concentration of corticosterone were evaluated. HAEMO (75 and 150 mg kg-1 ) significantly reversed anxiety- and depressive-like behaviours. Also, HAEMO reduced MDA levels, enhanced enzymatic antioxidant activities and restored serum levels of corticosterone. An immunoblotting analysis also demonstrated that HAEMO decreased levels of pro-apoptotic markers and increased anti-apoptotic protein levels in the prefrontal cortex and hippocampus of restraint stress-exposed mice. Our findings suggested that HAEMO reduced inflammation and had anxiolytic and antidepressant effects in mice.

The role of hippocampal GABAA receptors on anxiolytic effects of Echium amoenum extract in a mice model of restraint stress.

Echium amoenum (EA), a popular medicinal plant in Persian medicine, has anxiolytic, antioxidant, sedative, and anti-inflammatory effects. This study examined whether GABA-ergic signaling is involved in the anxiolytic effects of EA in mice. Sixty BALB/c mice (25-30 g) were divided into six groups (n = 10) as follows: the (I) control group received 10 ml/kg normal saline (NS). In the stress groups, the animals underwent 14 consecutive days of restraint stress (RS), and received following treatments simultaneously; (II) RS + NS; (III) RS + Diaz (Diazepam); (IV) RS + EA; (V) RS + Flu (Flumazenil) + EA; (VI) RS + Flu + Diaz. Behavioral tests including the open field test (OFT) and elevated plus maze (EPM) were performed to evaluate anxiety-like behaviors and the effects of the regimens. The plasma level of corticosterone and the hippocampal protein expressions of IL-1ß, TNF-α, CREB, and BDNF, as well as p-GABAA/GABAA ratio, were also assessed. The findings revealed that chronic administration of EA alone produced anxiolytic effects in both behavioral tests, while diazepam alone or in combination with Flu failed to decrease the anxiety-like behaviors. Furthermore, the p-GABAA/GABAA and p-CREB/CREB ratios, and protein levels of BDNF were significantly increased in the EA-received group. On the other hand, plasma corticosterone levels and the hippocampal IL-1ß and TNF-α levels were significantly decreased by EA. However, pre-treatment with GABAA receptors (GABAA Rs) antagonist, Flu, reversed the anxiolytic and molecular effects of EA in the RS-subjected animals. Our findings confirmed that alternation of GABAAR is involved in the effects of EA against RS-induced anxiety-like behaviors, HPA axis activation, and neuroinflammation.

Medicinal Plants as Potential Hemostatic Agents.

PURPOSE: Medicinal plants with a variety of phytochemical ingredients remain a potential source for new drug discovery. The use of medicinal herbs in a wide range of diseases and symptoms, such as bleeding, is prevalent in traditional and ethno medicine worldwide. Thus, this work provides a comprehensive review of medicinal plants or their isolated compounds, with respect to their ethno-medicinal use, which have demonstrated the stimulating effect on the hemostasis process. METHODS: The relevant studies were withdrawn from electronic databases including Pubmed, EMBASE and Web of Science with a structured search methodology. RESULTS: The total of 17 medicinal plants with hemostatic activity were extracted. The most frequently studied plant families were Compositae, Lamiaceae, Fabaceae, and Asteraceae. Bioactive compounds exerting hemostatic activity included tannins, iridoid glycosides, glycoconjugate, lignan, saponins and phenolic compounds. The most attributed mechanisms include coagulation stimulation via increasing the factor XII activity and plasma fibrinogen levels, the fibrinolysis inhibition, vascular or smooth muscle constriction and platelet aggregation. The most important adverse effects of high dose extract or isolated compounds administration were hepatotoxicity and nephrotoxicity. CONCLUSION: This review provides a list of medicinal plants with hemostatic activity that could be used as valuable sources of new plant-based hemostatic agents. Furthermore, this could be practical in detecting possible interactions of plants with anticoagulant, antiplatelet, fibrinolytic and antifibrinolytic medications.