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Carbamate (CBs) is a class of insecticides which is being known as an important cause of intentional or accidental poisoning. CBs, cause carbamylation of acetylcholinesterase at neuronal synapses and neuromuscular junction. Exposure to CBs through skin contact, inhalation, or ingestion can result in significant cholinergic toxicity. This is due to the elevation of acetylcholine levels at ganglionic synapses found in both the sympathetic and parasympathetic nervous systems, as well as muscarinic receptors located in target organs of the parasympathetic nervous system, nicotinic receptors situated in skeletal muscle tissue, and the central nervous system. The association between human illnesses and environmental exposures to CBs have been extensively studied in several studies. Although CBs-triggered toxicity leads to overproduction of reactive oxygen species (ROS), the detailed association between the toxicity under CBs exposure and NFE2-related factor 2 (Nrf2) signaling pathways has not been completely clarified. In this review we aimed to summarize the latest findings on the functional interrelationship between carbamates compounds and Nrf2 signaling.

The rising incidence of breast cancer has been a significant source of concern in the medical community. Regarding the adverse effects and consequences of current treatments, cancers' health, and socio-economical aspects have become more complicated, leaving research aimed at improved or new treatments on top priority. Medicinal herbs contain multitarget compounds that can control cancer development and advancement. Owing to Nigella Sativa's elements, it can treat many disorders. Thymoquinone (TQ) is a natural chemical derived from the black seeds of Nigella sativa Linn proved to have anti-cancer and anti-inflammatory properties. TQ interferes in a broad spectrum of tumorigenic procedures and inhibits carcinogenesis, malignant development, invasion, migration, and angiogenesis owing to its multitargeting ability. It effectively facilitates miR-34a up-regulation, regulates the p53-dependent pathway, and suppresses Rac1 expression. TQ promotes apoptosis and controls the expression of pro- and anti-apoptotic genes. It has also been shown to diminish the phosphorylation of NF-B and IKK and decrease the metastasis and ERK1/2 and PI3K activity. We discuss TQ's cytotoxic effects for breast cancer treatment with a deep look at the relevant stimulatory or inhibitory signaling pathways. This review discusses the various forms of polymeric and non-polymeric nanocarriers (NC) and the encapsulation of TQ for increasing oral bioavailability and enhanced in vitro and in vivo efficacy of TQ-combined treatment with different chemotherapeutic agents against various breast cancer cell lines. This study can be useful to a broad scientific community, comprising pharmaceutical and biological scientists, as well as clinical investigators.

Organophosphate compounds (OPCs) are a diverse class of chemicals utilized in both industrial and agricultural settings. The exact molecular pathways that OPCs-induced toxicity is caused by are still being investigated, despite the fact that studies on this topic have been ongoing for a long time. As a result, it's important to identify innovative strategies to uncover these processes and further the understanding of the pathways involved in OPCs-induced toxicity. In this context, determining the role of microRNAs (miRs) in the toxicity caused by OPCs should be taken into consideration. Recent research on the regulation function of miRs presents key discoveries to identify any gaps in the toxicity mechanisms of OPCs. As diagnostic indicators for toxicity in people exposed to OPCs, various expression miRs can also be used. The results of experimental and human studies into the expression profiles of miRs in OPCs-induced toxicity have been compiled in this article.

Abstract The aim of the present study was to investigate the protective effect of the Sophora pachycarpa (S. pachycarpa) seed extract against carbon tetrachloride-induced toxicity on body organs, blood, and biochemical factors. In this investigation, 40 male Wistar rats weighing 200–250 g were randomly divided into 5 groups: group I was used as control, group II received carbon tetrachloride (CCl4) (IP, 1 mL/kg) on day 21, group III and group IV received S. pachycarpa seed extract at doses of 150 mg/kg and 300 mg/kg, respectively for 21 days by oral gavage and CCl4 on day 21, group V received silymarin (300 mg/kg) for 21 days by oral gavage and CCl4 on day 21. CCl4 showed an increase of serum renal and hepatic markers creatinine, urea, blood urea nitrogen (BUN), and uric acid, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Also, it significantly increased MDA level, and decreased CAT, FRAP, GSH, and SOD in the liver and kidney tissues. These changes and also hematological and histopathological alterations were significantly ameliorated by S. pachycarpa seed extract before CCl4 administration. In conclusion, the data obtained in our investigation confirm the protective effect of S. pachycarpa against acute exposure to CCl4-induced organ toxicity in rats.

Background: The effect of opioids administration during lactation on nervous system has not fully understood. Objective: The aim of this study was to evaluate the buprenorphine (BUP) impact on oxidative stress indexes and apoptotic gene expression in the hippocampus of neonates exposed to this drug through breastfeeding. Methods: Lactating female rats were subcutaneously injected with BUP (1 or 0.5 mg/kg). After 28 days, the pups were anesthetized, then their hippocampus were obtained for measurement of oxidative stress parameters [glutathione (GSH), thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC) and superoxide dismutase (SOD)] and gene expression of apoptotic indices (Bcl2, Bax and caspase 3). Results: This study showed that BUP (0.5 and 1 mg/kg) could not markedly change oxidative stress indices levels and apoptotic markers expression in the hippocampus of pups versus controls. Conclusion: This study did not find BUP effect on the apoptosis and oxidative stress indices in the hippocampus of pups born to mothers exposed to this drug during lactation.

Abstract Regarding the epidemiological studies, neurological dysfunctions caused by cerebral ischemia or neurodegenerative diseases (NDDs) have been considered a pointed matter. Mount-up shreds of evidence support that both autophagy and reactive oxygen species (ROS) are involved in the commencement and progression of neurological diseases. Remarkably, oxidative stress prompted by an increase of ROS threatens cerebral integrity and improves the severity of other pathogenic agents such as mitochondrial damage in neuronal disturbances. Autophagy is anticipated as a cellular defending mode to combat cytotoxic substances and damage. The recent document proposes that the interrelation of autophagy and ROS creates a crucial function in controlling neuronal homeostasis. This review aims to overview the cross-talk among autophagy and oxidative stress and its molecular mechanisms in various neurological diseases to prepare new perceptions into a new treatment for neurological disorders. Furthermore, natural/synthetic agents entailed in modulation/regulation of this ambitious cross-talk are described.

The study investigated the effect of buprenorphine (BUP) on oxidative indices and gene expression of apoptotic molecules in the hippocampus of neonates during the fetal stage. BUP (1 or 0.5 mg/kg) was subcutaneously administrated to pregnant rat dams. After parturition, the pups were maintained to the end of breastfeeding period, then hippocampi were assessed for oxidative stress indices [glutathione (GSH), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), total antioxidant capacity (TAC)] and mRNA expression of apoptotic markers (Bax, Bcl2 and caspase 3). Our data indicated that BUP (0.5 mg/kg) administration during gestation significantly increased GSH and TAC concentrations in the hippocampus of pups versus control group (p

Abstract Aim and background Cancer represents a major health problem with an exceedingly high toll on the patients, their families, and the economy. Cancers are also associated with high mortality rates. Existing therapies for cancer are generally ineffective with many side effects. Method A search was conducted on Pubmed, Google Scholar, Scopus, and web of science databases, and articles related to anticancer effects of resveratrol were collected. Results Resveratrol is a natural compound that can activate the Nrf2 transcription factor. Nfr2 translocates to the nucleus and induces antioxidant gene expression. In different cell lines, resveratrol can increase apoptosis and inhibit the proliferation of cancer cells. Conclusion We found that resveratrol shows efficacy for the treatment of cancer, but due to high controversy on the Nrf2 signaling pathway and mechanisms of resveratrol action, additional studies should be conducted to better characterize its mode-of-action in cancer. Graphical Abstract

Abstract Signal transducer and activator of transcription 3 (STAT3) induces breast cancer malignancy. Recent clinical and preclinical studies have demonstrated an association between overexpressed and activated STAT3 and breast cancer progression, proliferation, metastasis, and chemoresistance. Resveratrol (RES), a naturally occurring phytoalexin, has demonstrated anti-cancer activity in several disease models. Furthermore, RES has also been shown to regulate the STAT3 signaling cascade via its anti-oxidant and anti-inflammatory effects. In the present review, we describe the STAT3 cascade signaling pathway and address the therapeutic targeting of STAT3 by RES as a tool to mitigate breast cancer.

Abstract Aging is the leading risk factor for several age-associated diseases such as neurodegenerative diseases. Understanding the biology of aging mechanisms is essential to the pursuit of brain health. In this regard, brain aging is defined by a gradual decrease in neurophysiological functions, impaired adaptive neuroplasticity, dysregulation of neuronal Ca2+ homeostasis, neuroinflammation, and oxidatively modified molecules and organelles. Numerous pathways lead to brain aging, including increased oxidative stress, inflammation, disturbances in energy metabolism such as deregulated autophagy, mitochondrial dysfunction, and IGF-1, mTOR, ROS, AMPK, SIRTs, and p53 as central modulators of the metabolic control, connecting aging to the pathways, which lead to neurodegenerative disorders. Also, calorie restriction (CR), physical exercise, and mental activities can extend lifespan and increase nervous system resistance to age-associated neurodegenerative diseases. The neuroprotective effect of CR involves increased protection against ROS generation, maintenance of cellular Ca2+ homeostasis, and inhibition of apoptosis. The recent evidence about the modem molecular and cellular methods in neurobiology to brain aging is exhibiting a significant potential in brain cells for adaptation to aging and resistance to neurodegenerative disorders.

Abstract Chrysin has been shown to exert several beneficial pharmacological activities. Chrysin has anti-cancer, anti-viral, anti-diabetic, neuroprotective, cardioprotective, hepatoprotective, and renoprotective as well as gastrointestinal, respiratory, reproductive, ocular, and skin protective effects through modulating signaling pathway involved in apoptosis, oxidative stress, and inflammation. In the current review, we discussed the emerging cellular and molecular mechanisms underlying therapeutic indications of chrysin in various cancers. Online databases comprising Scopus, PubMed, Embase, ProQuest, Science Direct, Web of Science, and the search engine Google Scholar were searched for available and eligible research articles. The search was conducted by using MeSH terms and keywords in title, abstract, and keywords. In conclusion, experimental studies indicated that chrysin could ameliorate cancers of the breast, gastrointestinal tract, liver and hepatocytes, bladder, male and female reproductive systems, choroid, respiratory tract, thyroid, skin, eye, brain, blood cells, leukemia, osteoblast, and lymph. However, more studies are needed to enhance the bioavailability of chrysin and evaluate this agent in clinical trial studies. Graphic abstract

Introduction: Our aim was to investigate and evaluate the influence of metformin on cancer-related biomarkers in clinical trials. Methods: This systematic study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Major databases, including Scopus, Web of Sciences, PubMed, Ovid-Medline, and Cochrane, were systematically reviewed by February 2020. Clinical trials investigating metformin effects on the evaluation of homeostatic models of insulin resistance (HOMA-IR), Ki-67, body mass index (BMI), fasting blood sugar (FBS), and insulin were selected for further analysis. Quality assessment was performed with version 2 of the Cochrane tool for determining the bias risk for randomized trials (RoB 2). Heterogeneity among the included studies was assessed using the Chi-square test. After quality assessment, a random effects model was performed to summarize the data related to insulin, HOMA-IR, Ki-67, and a fixed-effect model for FBS and BMI in a meta-analysis. Results: Nine clinical trials with 716 patients with operable breast and endometrial cancer and 331 with primary breast cancer were involved in the current systematic and meta-analysis study. Systematic findings on the nine publications indicated metformin decreased insulin levels in four studies, FBS in one, BMI in two, Ki-67 in three studies, and HOMA-IR in two study. The pooled analysis indicated that metformin had no significant effect on the following values: insulin (standardized mean differences (SMD) = −0.87, 95% confidence intervals (CI) (−1.93, 0.19), p = 0.11), FBS (SMD = −0.18, 95% CI (−0.30, −0.05), p = 0.004), HOMA-IR (SMD = −0.17, 95% CI (−0.52, 0.19), p = 0.36), and BMI (SMD = −0.13, 95% CI (−0.28, 0.02), p = 0.09). Metformin could decrease Ki-67 in patients with operable endometrial cancer versus healthy subjects (SMD = 0.47, 95% CI (−1.82, 2.75), p = 30.1). According to Egger’s test, no publication bias was observed for insulin, FBS, BMI, HOMA-IR, and Ki-67. Conclusions: Patients with operable breast and endometrial cancer under metformin therapy showed no significant changes in the investigated metabolic biomarkers in the most of included study. It was also found that metformin could decrease Ki-67 in patients with operable endometrial cancer. In comparison to the results obtained of our meta-analysis, due to the high heterogeneity and bias of the included clinical trials, the present findings could not confirm or reject the efficacy of metformin for patients with breast cancer and endometrial cancer.

Abstract Gastric cancer (GC) is one of the most common cancers with high malignancy. In spite of the great development in diagnostic tools and application of anti-tumor drugs, we have not witnessed a significant increase in the survival time of patients with GC. Multiple studies have revealed that Wnt, Nrf2, MAPK, and PI3K/Akt signaling pathways are involved in GC invasion. Besides, long non-coding RNAs and microRNAs function as upstream mediators in GC malignancy. GC cells have acquired resistance to currently applied anti-tumor drugs. Besides, combination therapy is associated with higher anti-tumor activity. Resveratrol (Res) is a non-flavonoid polyphenol with high anti-tumor activity used in treatment of various cancers. A number of studies have demonstrated the potential of Res in regulation of molecular pathways involved in cancer malignancy. At the present review, we show that Res targets a variety of signaling pathways to induce apoptotic cell death and simultaneously, to inhibit the migration and metastasis of GC cells.

Abstract Application of novel methods in cancer therapy is important in terms of management and treatment of the life-threatening disorder. It appears that autophagy is a potential target in cancer therapy, as a variety of drugs targeting autophagy have shown great potential in reducing the viability and proliferation of cancer cells. Autophagy is primarily a catabolic process which provides energy during starvation. Besides, this process contributes to the degradation of aged or potentially toxic components and organelles. On the other hand, the source of a variety of naturally occurring anti-tumor drugs are flavonoids which have high anti-tumor activity. Luteolin is a polyphenolic flavone with the great pharmacological effects such as anti-diabetic, hepatoprotective, antioxidant, anti-inflammation, and anti-tumor. At the present review, we demonstrate how luteolin affects on autophagy process to induce anti-tumor activity.

Abstract There have been attempts to develop novel anti-tumor drugs in cancer therapy. Although satisfying results have been observed at a consequence of application of chemotherapeutic agents, the cancer cells are capable of making resistance into these agents. This has forced scientists into genetic manipulation as genetic alterations are responsible for generation of a high number of cancer cells. MicroRNAs (miRs) are endogenous, short non-coding RNAs that affect target genes at the post-transcriptional level. Increasing evidence reveals the potential role of miRs in regulation of biological processes including angiogenesis, metabolism, cell proliferation, cell division, and cell differentiation. Abnormal expression of miRs is associated with development of a number of pathologic events, particularly cancer. MiR-93 plays a significant role in both physiological and pathological mechanisms. At the present review, we show how this miR dually affects the proliferation and invasion of cancer cells. Besides, we elucidate the oncogenesis or oncosuppressor function of miR-93.

The over-activated microglial cells induce neuroinflammation which has the main role in neurological disorders. The over-activated microglia can disturb neuronal function by releasing inflammatory mediators leading to neuronal dysfunctions and death. Thus, inhibition of over-activated microglia may be an effective therapeutic approach for modulating neuroinflammation. Experimental studies have indicated anti-neuroinflammatory effects of flavonoids such as green tea catechins. The current research was aimed to review the effect of green tea catechins in inhibiting microglial cells, inflammatory cascades, and subsequent neurological diseases.

Astaxanthin (AST) is a red pigmented carotenoid with significant antioxidant, anti-inflammatory, anti-proliferative, and anti-apoptotic properties. In this study, we summarize the available literature on the anti-inflammatory efficacy of AST in various chronic and acute disorders, such as neurodegenerative, renal-, hepato-, skin- and eye-related diseases, as well as gastrointestinal disorders. In addition, we elaborated on therapeutic efficacy of AST and the role of several pathways, including PI3K/AKT, Nrf2, NF-κB, ERK1/2, JNK, p38 MAPK, and JAK-2/STAT-3 in mediating its effects. However, additional experimental and clinical studies should be performed to corroborate the anti-inflammatory effects and protective effects of AST against inflammatory diseases in humans. Nevertheless, this review suggests that AST with its demonstrated anti-inflammatory property may be a suitable candidate for drug design with novel technology.

The complexity of today's modern society, increasing problems and changes in lifestyles can lead to stress and anxiety in people. To control stress and anxiety, sedative drugs that have anxiolytic and sedative effects and temporarily calm the person and lead to a pleasant sleep are used. However, it must also be kept in mind that each of these drugs have their own side effects. Being sedative is one of the reported properties of some herbal drugs. The use of these materials can be beneficial and will not cause side effects like those of conventional sedative drugs. The use of oral herbal drugs is one of the ancient methods that have been used to control anxiety, stress and pain. Besides, numerous side effects of chemical drugs have caused a renewed tendency to using herbal medicine. Therefore, this study is aimed to introduce some of the most effective medicinal plants with sedative properties based on Iranian ethnobotanical documents.

Neurological diseases are responsible for a large number of morbidities and mortalities in the world. Flavonoids are phytochemicals that possess various health-promoting impacts. Chrysin, a natural flavonoid isolated from diverse fruits, vegetables, and even mushrooms, has several pharmacological activities comprising antioxidant, anti-inflammatory, antiapoptotic, anticancer, and neuroprotective effects. The current study was designed to review the relationship between chrysin administration and neurological complications by discussing the feasible mechanism and signaling pathways. Herein, we mentioned the sources, pharmacological properties, chemistry, and drug delivery systems associated with chrysin pharmacotherapy. The role of chrysin was discussed in depression, anxiety, neuroinflammation, Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy, cerebral ischemia, spinal cord injury, neuropathy, Multiple Sclerosis, and Guillain-Barré Syndrome. The findings indicate that chrysin has protective effects against neurological conditions by modulating oxidative stress, inflammation, and apoptosis in animal models. However, more studies should be done to clear the neuroprotective effects of chrysin.

Gastrointestinal cancer is one of the most common cancers globally. Melatonin, a natural endogenous body hormone, has been of interest for years, due to its anti-cancer characteristics, such as antiproliferative, antimetastatic, and cytotoxic as well as apoptotic induction. Through regulating several proteins such as melatonin upregulated mRNAs and proteins of downregulated Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2), as well as cytoplasmic protein such as calcium-binding proteins calmodulin or tubulin, and nuclear receptors, including RORα/RZR, and acts by non-receptor-regulated mechanisms, melatonin can exert anti-cancer efficacy. Moreover, melatonin modulates angiogenesis by targeting mRNA and protein expression of endothelin-converting enzyme (ECE-1) protein. In the present review, we address in vivo, in vitro and clinical reports on its anti-cancer efficacies, and the molecular mechanisms of action responsible for these effects. We advance the possibility of therapeutic melatonin administration for cancer therapy.

Thymoquinone (TQ, 2-methyl-5-isopropyl-1, 4-benzoquinone), a monoterpene molecule present in Nigella sativa L., has an anti-inflammatory, anti-oxidant, and anti-apoptotic properties in several disorders such as asthma, hypertension, diabetes, inflammation, bronchitis, headache, eczema, fever, dizziness and influenza. TQ exerts its anti-inflammatory and anti-oxidant effects via several molecular pathways, including the release of cytokines, and activation of cyclooxygenase-2 (COX2), nuclear factor erythroid 2–related factor 2 (Nrf2), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), nuclear factor kappa-light-chain-enhancer of activated B (NF-Κβ). In this review, recent reports on the anti-inflammatory efficacy of TQ in heart disorders, respiratory diseases, neuroinflammation, diabetes and arthritis are summarized. We suggest that further investigation is necessary to better characterize the efficacy of TQ as a therapeutic agent.

Astaxanthin (ATX) is a red pigment carotenoid present in shrimp, salmon, crab, and asteroidean. Several studies have corroborated the anti-oxidant efficacy of ATX. In addition, ATX has anti-inflammatory, anti-apoptotic and anti-proliferative properties. In the present review, we discuss the role of Nrf2 in mediating the anti-cancer, anti-aging, neuroprotective, lung-protective, skin-protective, cardioprotective, hepatoprotective, anti-diabetic and muscloprotective effects of ATX.

Advanced age is a major risk factor for metabolic disorders. Accelerated inflammatory processes with increased age can contribute to the pathogenesis of metabolic disturbances. Chrysin is a natural flavonoid ingredient of honey and propolis. Chrysin has been effective in decreasing cholesterol and glucose levels preventing metabolic disturbances. The aim of this study was to evaluate the effects of chrysin against age-associated inflammation, hyperglycemia, and hypercholesterolemia. Male Wistar rats (2, 10, and 20 month-old) were intraperitoneally (i.p.) injected with chrysin (20 mg/kg) for 30 days. The findings showed elevated inflammatory cytokines, glucose, and lipid parameters in the sera of aged rats when compared with young ones. However, chrysin treatment ameliorated these alterations. Furthermore, chrysin reduced the levels of adiponectin, HDL-C, and insulin in 20 month-old rats. The current study showed that chrysin was effective in attenuating age-related lipid abnormalities, glucose elevation, and inflammation.

Introduction: The perennial herb saffron belongs to the Lily family. From ancient times, saffron as traditional medicine is used as an effective drug for treatment of eye, nervous system, digestive system, kidney, cardiovascular, respiratory, and reproductive systems disorders. Pharmacological research has shown the antioxidant, anti-inflammatory, and anti-apoptotic effects of saffron and its compounds. However, reports have been made on the toxic effects of saffron and its active substances (Crocin, Crosteen, Safranal). This review considered the scientific literature on the toxic effects of saffron and its active ingredients. Methods: We searched the literature for basic and clinical studies concerned with the toxic effects of saffron and its active compounds. The electronic databases including PubMed-Medline, Embase, Google Scholar, and Scopus were searched till to 2019. Keywords were crocus sativus, saffron, safranal, toxicity, crocetin, crocin, picrocrocin combined in different ways to retrieve related articles. Results: The present study provides information on the organic toxicity of saffron and its active components, as well as their side effects in humans. The results of this study showed that the therapeutic doses of saffron and its active ingredients do not induce toxic effects in clinical or experimental studies. Conclusion: Due to the reported toxic effects of saffron and its components in humans, thus the safety of this plant is unclear. It seems that the use of high doses of saffron, especially for pregnant women, should be taken with more care.

Cardiovascular diseases (CVDs) are one of the leading causes of the most considerable mortality globally, and it has been tried to find the molecular mechanisms and design new drugs that triggered the molecular target. Curcumin is the main ingredient of Curcuma longa (turmeric) that has been used in traditional medicine for treating several diseases for years. Numerous investigations have indicated the beneficial effect of Curcumin in modulating multiple signaling pathways involved in oxidative stress, inflammation, apoptosis, and proliferation. The cardiovascular protective effects of Curcumin against CVDs have been indicated in several studies.In the current review study, we provided novel information on Curcumin's protective effects against various CVDs and potential molecular signaling targets of Curcumin. Nonetheless, more studies should be performed to discover the exact molecular target of Curcumin against CVDs.

Coronavirus disease 2019 (COVID-19) is a viral pneumonia that is spreading rapidly worldwide. The main feature of this disease is a severe acute respiratory syndrome and caused by coronavirus 2 (SARS-CoV-2). There are several unknowns about the pathogenesis and therapeutically treatment of COVID-19 infection. In addition, available treatment protocols have not been effective in managing COVID-19 infection. It is proposed that natural anti-oxidants such as lemon, green tea, saffron, curcuma longa, etc. with high flavonoids like safranal, crocin, crocetin, catechins, resveratrol, calebin A, curcumin have therapeutic potential against viral infections. In this context, honey and its main components are being investigated as an option for patients with COVID-19. The present study may indicate that honey and its main components inhibit the entry of the virus into the host cell and its replication as well as modulate the inflammatory cascade. This review provides basic information for the possible potential effects of honey and its main components for fighting with SARS-CoV-2.

Healthy aging and human longevity are intricate phenotypes affected by environmental factors such as physical exercise, diet, health habits, and psychosocial situations as well as genetic factors. Diet and caloric restriction have a crucial role in healthy aging. Curcumin, a polyphenolic compound isolated from the Curcuma longa, has been shown to exert anti-aging characteristics. Recently, investigations on curcumin with regard to aging and age-associated disease in model organisms has described that curcumin and its metabolites, prolong the mean lifespan of some aging model organisms such as C. elegans, D. melanogaster, yeast, and mouse. It has been proposed to have several biological activities, such as antioxidative, anti-inflammatory, anticancer, chemopreventive, and anti-neurodegenerative characteristics. In several studies on various model organisms it has been shown that the lifespan extension via curcumin treatment was connected with enhanced superoxide dismutase (SOD) activity, and also declined malondialdehyde (MDA) and lipofuscin levels. As well as the pivotal role of curcumin on the modulating of major signaling pathways that influence longevity of organisms like IIS, mTOR, PKA, and FOXO signaling pathways. This review defines the use of curcumin in traditional and modern medicine, its biochemistry and biological functions, such as curcumin's anti-aging, anti-cancer, anti-microbial, anti-inflammatory, and anti-oxidant characteristics. Also, the review further describes the role of curcumin in a pharmacological context and new insights on its therapeutic capacity and restrictions. Particularly, the review emphasizes in-depth on the efficiency of curcumin and its mechanism of action as an anti-aging compound and also treating age-related disease.

Alzheimer’s disease (AD) is a neurodegenerative condition mostly communal in people of advanced years accompanying various dysfunctionalities especially cognitive impairments. A number of cellular damages, such as amyloid-beta aggregation, tau protein hyperphosphorylation, some neurotransmitter imbalances, apoptosis, oxidative stress, and inflammatory responses are responsible for AD incidence. As a reason for inadequate efficacy, side effects, and pharmacokinetic problems of conventional drugs used for AD, the discovery of novel therapeutic agents with multi-targeted potential is desirable. Protective properties of phytochemicals combat numerous diseases and their vast acceptance and demand in human beings encouraged scientists to assess their effective activities. Zingiber officinale, gingerol, shogaol, and borneol were evaluated against memory impairments. Online databases including; Web of Science, Scopus, Embase, Pubmed, ProQuest, ScienceDirect, and Cochrane Library were searched until 3th February 2020. In vitro, in vivo, and clinical studies are included after screening their eligibility. Mostly interventive mechanisms such as; oxidative stress, neuroinflammation, and apoptosis are described. Correlation between the pathogenesis of AD and signaling pathways is explicated. Results and scores of cognition measurements are clarified due to in vivo studies and clinical trials. Some traditional aspects of consuming ginger in AD are also mentioned in the present review. In accumulation ginger and its components possess great potency for improving and abrogating memory dysfunctions but conducting further studies to evaluate their pharmacological and pharmaceutical aspects is required.

Honey and its phenolic compounds specifically chrysin are focused as nutritional supplements and likewise as valued phytochemicals, nutraceuticals, and phytopharmaceuticals alone, or adjuvant with some conventional medications to cause synergistic therapeutic or cytotoxic effects. Through the verified beneficial strategies combat several disturbances, phenolic compounds play fundamental functions in the avoidance and treatment of disorders. Oxidative stress, inflammation, and apoptosis are the three most imperative physiological reactions in the prevalence of numerous ailments. Honey, chrysin, and other phenolic compounds detected in honey can modify clinical conditions via modulation of these contrivances and correlated signaling pathways. The current study desires to review the therapeutic effects of honey and its allied molecular mechanisms. Evidenced-base studies show that honey would represent therapeutic potential against various types of cancer and tumor proliferation (colorectal cancer, breast cancer, bladder cancer, leukemia, glioma, hepatocellular cancer, pancreatic cancer, and melanoma), wounds, diabetes mellitus, neurological (depression, Parkinson disease, and Alzheimer's disease), respiratory, gastrointestinal (peptic ulcer and ulcerative colitis), cardiovascular disorders, renal injuries, liver diseases and many other kinds of physiological dysfunctionalities through various molecular mechanisms contributed with oxidative stress, inflammatory process, and apoptosis.

Resveratrol is a natural polyphenol derived from grapes, berries, red wine, peanuts amongst other fruits and nuts. Beneficial effects such as anti-inflammatory, antioxidant, hepatoprotective, neuroprotective, cardioprotective, renoprotective, anti-obesity, anti-diabetic, and anti-cancer of resveratrol have been demonstrated by preclinical and clinical research. A possibility is that these therapeutical effects are associated with modulation of the Nrf2 signaling pathway in the following way: resveratrol may potentiate Nrf2 signaling through blockage of Keap1, by means of changing the Nrf2 mediators, its expression and its nuclear translocation. This article reviews the evidence of the Nrf2 modulating hypothesis as a possible molecular mechanism underlying the medicinal properties of resveratrol.

Background: Pediatric stroke is defined as rapid developing clinical signs of focal (or global) disturbance of cerebral function without any apparent cause other than of vascular origin lasting for 24 hours or longer in the ages of 1 month to 18 years. It is relatively rare in children, however, it can lead to significant mortality and morbidity. Objectives: The present study aimed to identify clinical presentations, etiologies, and outcomes of pediatric stroke in southern Iran. Methods: This case-series study included all patients that were diagnosed with a pediatric stroke and admitted to the Pediatric Neurology ward at Namazi hospital in Shiraz, Iran, from May 2009 through March 2012. Results: During the study period, 40 newly diagnosed patients (27 males and 13 females) between the ages of 10 months and 18 years old were identified. The most prevalent referring symptoms were hemiparesis and hemiplagia (65%), seizures (45%), speech difficulties (42.5%), and altered mental status (35%). A known single etiology was identified in 82.5% of patients. The most common single risk factor was cardiac abnormalities with 30% frequency, followed by idiopathic and vascular with 17.5%. The outcome of pediatric patients revealed incomplete recovery with moderate neurological deficits (45%) including residual epilepsy (15%), speech difficulties (15%), and behavioral dysfunction (7%), which indicate their need for help in some of their daily activities. Conclusions: Stroke in southern Iranian pediatric patients demonstrated different patterns of causes and risk factors with similar clinical presentations and outcomes.

Nitric Oxide (NO) is a potent signaling molecule involved in the regulation of various cellular mechanisms and pathways under normal and pathological conditions. NO production, its effects, and its efficacy, are extremely sensitive to aging-related changes in the cells. Herein, we review the mechanisms of NO signaling in the cardiovascular system, central nervous system (CNS), reproduction system, as well as its effects on skin, kidneys, thyroid, muscles, and on the immune system during aging. The aging-related decline in NO levels and bioavailability is also discussed in this review. The decreased NO production by endothelial nitric oxide synthase (eNOS) was revealed in the aged cardiovascular system. In the CNS, the decline of the neuronal (n)NOS production of NO was related to the impairment of memory, sleep, and cognition. NO played an important role in the aging of oocytes and aged-induced erectile dysfunction. Aging downregulated NO signaling pathways in endothelial cells resulting in skin, kidney, thyroid, and muscle disorders. Putative therapeutic agents (natural/synthetic) affecting NO signaling mechanisms in the aging process are discussed in the present study. In summary, all of the studies reviewed demonstrate that NO plays a crucial role in the cellular aging processes.

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) is a specific transcription factor with potent effects on the regulation of antioxidant gene expression that modulates cell hemostasis under various conditions in tissues. However, the effects of Nrf2 on gastric cancer (GC) are not fully elucidated and understood. Evidence suggests that uncontrolled Nrf2 expression and activation has been observed more frequently in malignant tumors, including GC cells, which is then associated with increased antioxidant capacity, chemoresistance, and poor clinical prognosis. Moreover, Nrf2 inhibitors and the associated modulation of tumor cell redox balance have shown that Nrf2 also has beneficial effects on the therapy of various cancers, including GC. Based on previous findings on the important role of Nrf2 in GC therapy, it is of great interest to scientists in basic and clinical tumor research that Nrf2 can be active as both an oncogene and a tumor suppressor depending on different background situations.

Abstract Background Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research focused the protective effect of carnosol against the brain injury induced by the restraint stress. Methods The restraint stress induced by keeping animals in restrainers for 21 consecutive days. Thereafter, the rats were injected carnosol or vehicle for 21 consecutive days. At the end of experiment, all the rats were subjected to his open field test and forced swimming test. Afterwards, the rats were sacrificed for measuring their oxidative stress parameters. To measure the modifications in the biochemical aspects after the experiment, the activities of malondialdehyde (MDA), reduced glutathione (GSH), as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were evaluated in the whole brain. Results Our data showed that the animals received chronic stress had a raised immobility time versus the non-stressed animals (p

Introduction: Crocus sativus L. (saffron) has many biological effects such as antioxidant property. The present study investigated the immunomodulatory effects of the aqueous saffron extract on streptozotocin (STZ)-induced diabetic rats. Materials and methods: In this study, the rats were divided into the following groups of 9 animals each: control, untreated diabetic, three saffron extract-treated diabetic groups. Diabetes was induced by STZ in rats. Saffron was administered 3 days after STZ administration; these injections were continued to the end of the study (4 weeks). At the end of the 4-week period, blood was drawn for biochemical assays and the abdominal aorta was removed for detecting the inflammatory cytokines expression. Results: We found that saffron decreased blood glucose, malondialdehyde, nitric oxide, total lipids, triglycerides, cholesterol levels significantly (p

The aim of this study was to evaluate the effect of banana leaf extract on the quality and shelf life of rainbow trout compared to plastic bags at freezing temperature for 40 days. For evaluating this propose, the antioxidant activity of banana leaf extract was assessed. In addition, the shelf life of fish filets was determined by measuring thiobarbituric acid (TBA) and pHof fish. The banana leaves extract showed the highest content of vitamin E (5.8 ± 0.61 mg /g) and carotenoids (12.8 ± 0.1 mg /g). The potential of Cu (II) reduction the extract was 1.76 ± 0.09. The magnitude of modification in TBA and pH of the packed fish with banana leaves were less than the control samples. The present study demonstrated that the use of banana leaf extract will retard lipid oxidation in fish. fillet during freezing storage that may due to its strong antioxidant properties.

Obesity as an independent risk factor for cardiovascular diseases (CVDs) leads to an increase in morbidity, mortality, and a shortening of life span. The changes in heart structure and function as well as metabolic profile are caused by obese people, including those free of metabolic disorders. Obesity alters heart function structure and affects lipid and glucose metabolism, blood pressure, and increase inflammatory cytokines. Adipokines, specific cytokines of adipocytes, are involved in the progression of obesity and the associated co-morbidities. In the current study, we review the scientific evidence on the effects of obesity on CVDs, focusing on the changes in adipokines. Several adipokines have anti-inflammatory and cardioprotective effects comprising omentin, apelin, adiponectin, and secreted frizzled-related protein (Sfrp-5). Other adipokines have pro-inflammatory impacts on the cardiovascular system and obesity including leptin, tumor necrosis factor (TNF), retinol-binding protein4 (RBP-4), visfatin, resistin, and osteopontin. We found that obesity is associated with multiple CVDs, but can only occur in unhealthy metabolic patients. However, more studies should be designed to clarify the association between obesity, adipokine changes, and the occurrence of CVDs.

The molecular signaling pathways that lead to cell survival/death after exposure to organophosphate compounds (OPCs) are not yet fully understood. Mitogen-activated protein kinases (MAPKs) including the extracellular signal-regulated protein kinase (ERK), the c-Jun NH2-terminal kinase (JNK), and the p38-MAPK play the leading roles in the transmission of extracellular signals into the cell nucleus, leading to cell differentiation, cell growth, and apoptosis. Moreover, exposure to OPCs induces ERK, JNK, and p38-MAPK activation, which leads to oxidative stress and apoptosis in various tissues. However, the activation of MAPK signaling pathways may differ depending on the type of OPCs and the type of cell exposed. Finally, different cell responses can be induced by different types of MAPK signaling pathways after exposure to OPCs.

Thymoquinone (TQ), one of the main components active of Nigella sativa , exhibited very useful biomedical effects such as anti-inflammatory, antioxidant, antimicrobial, antiparasitic, anticancer, hypoglycemic, antihypertensive, and antiasthmatic effects. There are several studies about pharmacological activities of TQ but its neuroprotection effects are not fully described. The literature search has indicated many studies pertaining to the effects of TQ in neurological problems such as epilepsy, parkinsonism, anxiety, and improvement of learning and memory, and so on. In addition, TQ protected brain cells from various injuries due to its antioxidant, anti-inflammatory, and apoptotic effects in cell line and experimental animal models. The present study has been designed to review the scientific literature about the pharmacological activities of TQ to the neurological diseases. This study purposed that although experimental studies indicated the beneficial effects of TQ against nervous system problems, better designed clinical trials in humans are needed to confirm these effects.

Introduction and Aims: Despite the restrictions for the use of lead-containing compounds in industry and services, it remains one of the main agents to create acute and chronic poisoning, particularly in industrialized countries in the world.Materials and Methods: We searched all published articles from 1980 to 2014 by using of web search engine such as ISI Web of Science, Science direct, PubMed and Scholar Google.Results: Several epidemiological studies indicate a possible role of this metal in exacerbation of asthma. Despite the development of therapeutic strategies for asthma and chronic obstructive pulmonary disease in humans and animals, the disease has not subsided and remains a serious threat for human and animal health. Finding of the etiologic relationship between these diseases and intoxications occupational, environmental, and sustainability-environmental could be replaced progress therapeutic approaches with an advanced proactive approach to achieve substantial progress. A present review study has been conducted to investigate the experimental and epidemiological studies the effects of lead exposure on the occurrence of the attack of asthma.Conclusion: The results indicate that lead may cause increased airways responsiveness, pathological changes and inflammatory responses in victim.* Corresponding Author: Tehran, Tehran University of Payam Noor, Department of Agriculture.Email: Farkhondeh2324@gmail.com

The present study was designed to investigate the protective effect of the aqueous extract of Portulaca oleracea against hyperglycemic, oxidative damage and inflammation in the serum of streptozotocin (STZ)-induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 Portulaca oleracea (100, 200, 400 mg/kg/d)–treated diabetic groups. At the end of the 4-week period, glucose, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), glutathione (GSH), and total antioxidant status (TAS) levels were measured. STZ caused an elevation in the serum levels of glucose, MDA, IL-6, and TNF-α with reduction in the levels of GSH and TAS ( P < .01). Portulaca oleracea ameliorated glucose, MDA, IL-6, TNF-α, GSH, and TAS levels in diabetic groups versus to the untreated groups ( P < .05). Taken together, Portulaca oleracea prevented hyperglycemia by preventing the oxidative stress and inflammation.

Issues: Polyphenolic compounds, especially flavonoids, are known as the most common chemical class of phytochemicals, which possess a multiple range of health-promoting effects. Flavonoids are ubiquitous in nature. They are also present in food, providing an essential link between diet and prevention of several diseases. Approach: Chrysin (CH), a natural flavonoid, was commonly found in propolis and honey and traditionally used in herbal medicine. A growing body of scientific evidence has shown that CH possesses protective effects against toxic agents in various animal tissues, including brain, heart, liver, kidney, and lung. Key Findings: This study found that CH may be effective in disease management induced by toxic agents. However, due to the lack of information on human, further studies are needed to determine the efficacy of CH as an antidote agent in human. Conclusion: The present article aimed to critically review the available literature data regarding the protective effects of CH against toxic agent–induced toxicities as well as its possible mechanisms.

Context: Diabetes mellitus causes atherosclerosis and lipid abnormalities. Hypolipidemic and antioxidative properties of catechin (CTN) have been reported in several studies. Objective: This study assesses the possible protective effects of CTN against oxidative damage in the diabetic rats. Materials and Methods: The rats were divided into the control, untreated diabetic, and 3 CTN-treated diabetic groups (20, 40, and 80 mg/kg/d, intraperitoneal). The diabetic rats were induced by streptozotocin. Catechin was injected for 4 weeks. At the end of the experimental period, glucose, lipid profile, apoprotein A-I (apo A-I), apoprotein B (apo B), malondialdehyde (MDA) levels, and antioxidant enzymes including glutathione- S -transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in serum. Statistical analyses were performed using the InStat 3.0 program. Results: Streptozotocin caused an elevation of glucose, MDA, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apo B with reduction in high-density lipoprotein cholesterol (HDL-C), apo A-I, SOD, CAT, and GST in the serum ( P < .05). The findings showed that the significant elevation in the body weight, glucose, MDA, TG, TC, LDL-C, and apo B and reduction in HDL-C, apo A-I, SOD, CAT, and GST were ameliorated in the CTN-treated diabetic groups versus the untreated group, in a dose-dependent manner ( P < .05). Conclusion: The present investigation proposes that CTN may ameliorate diabetes and its complications by modification of oxidative stress.

Restraint stress may be associated with elevated free radicals, and thus, chronic exposure to oxidative stress may cause tissue damage. Several studies have reported that carvacrol (CAR) has a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CAR on restraint stress induced oxidative stress damage in the brain, liver, and kidney. For chronic restraint stress, rats were kept in the restrainers for 6 h every day, for 21 consecutive days. The animals received systemic administrations of CAR daily for 21 days. To evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) activities were measured in the brain, liver, and kidney. In the stressed animals that received vehicle, the MDA level was significantly higher (P