Apoptosis-inducing Plant-based Phenolic Compounds are Effective on Leukemia Cell Lines.

Numerous natural compounds have been identified that are able to induce apoptosis in cancer cells. These compounds have various chemical properties and are found in medicinal plants, vegetables, and fruits that are commonly consumed by humans. Phenols represent important compounds, which have been demonstrated to induce apoptosis in cancer cells, and some of the involved mechanisms have also been determined. The most important and abundant phenolic compounds are tannins, caffeic acid, capsaicin, gallic acid, resveratrol, and curcumin. Induction of apoptosis with the least or no toxicity to natural tissues is one of the useful effects of many plant-based bioactive compounds. Phenols, with anticancer potency at different degrees, serve to induce apoptosis through different pathways, including both extrinsic (Fas) and intrinsic (calcium release, ROS increase, DNA degradation, and mitochondrial membrane impairment). In this review, we report these compounds and their apoptosis-inducing mechanisms. Apoptosis or programmed cell death is a precise and systematic mechanism that is aimed at removing damaged or abnormal cells and is very useful to control, treat, and prevent cancer. Apoptotic cells are characterized by specific morphological features and molecular expression. In addition to physiological stimuli, there are many external factors that can be useful for inducing apoptosis. Also, these compounds can affect the regulatory proteins of the apoptotic pathways, such as the apoptotic proteins (Bid and BAX) and antiapoptotic proteins (Bcl-2). Taking these compounds and their molecular mechanisms into account can help use them in combination with chemical drugs and develop new drugs.

Are Herbal-peptides Effective as Adjunctive Therapy in Coronavirus Disease COVID-19?

BACKGROUND: Plant antiviral peptides (AVP) are macromolecules that can inhibit the pathogenesis of viruses by affecting their pathogenic mechanism, but most of these peptides can bind to cell membranes, inhibit viral receptors, and prevent viruses. Recently, due to the coronavirus pandemic, the availability of appropriate drugs with low side effects is needed. In this article, the importance of plant peptides in viral inhibition, especially viral inhibition of the coronavirus family, will be discussed. METHODS: By searching the databases of PubMed, Scopus, Web of Science, the latest articles on plant peptides effective on the COVID-19 virus were collected and reviewed. RESULTS: Some proteins can act against the COVID-19 virus by blocking sensitive receptors in COVID-19, such as angiotensin-converting enzyme 2 (ACE2). The 23bp sequence of the ACE2 alpha receptor chain can be considered as a target for therapeutic peptides. Protease and RNAP inhibitors and other important receptors that are active against COVID-19 should also be considered. CONCLUSION: Herbal medicines with AVP, especially those with a long history of antiviral effects, might be a good choice in complement therapy against the COVID-19 virus.

Effects of Hyssopus Officinalis Hydroalcoholic Extract on Pentylenetetrazol-Induced Convulsive Seizures in Rat.

Hyssopus officinalis L. is one of the most important medicinal plants in traditional medicine used to treat seizures. In this study, we assessed the effects of H. officinalis hydroalcoholic extract against pentylenetetrazol (PTZ)-induced seizures in rat. The anti-seizure activity of the extract was assessed in three doses of 25, 50, and 100 mg/kg. Kindling was induced by intraperitoneal injection of PTZ (35 mg/kg) every 48 h, and H. officinalis extract was administered daily and behavioral tests performed. The possible involvement of GABA receptors in the extract activity was investigated using flumazenil. Tonic seizure threshold and mortality rate were measured following intraperitoneal injection of 60 mg/kg PTZ on the 14th day, following 14 days administration of H. officinalis hydroalcoholic extract. Blood and hippocampus samples were prepared to measure brain and serum antioxidant capacity, malondialdehyde (MDA), and nitric oxide (NO). Finally, the expression of GABA receptor gene in brain tissue was investigated. H. officinalis extract increased tonic seizure threshold and decreased mortality due to PTZ. Flumazenil, as a GABA receptor antagonist, reduced the tonic seizure threshold. Extract treatment significantly improved memory and learning, increased brain antioxidant capacity, decreased brain MDA and NO in kindled rats. It also increased GABA receptor gene expression in pre-treated groups compared to the negative control group. H. officinalis extract probably exerts potential antiepileptic effects through the GABAergic system. Also, H. officinalis extract has a supportive effect against hippocampal neuronal damage and improves memory and learning in kindled rats.

An Update on Promising Agents against COVID-19: Secondary Metabolites and Mechanistic Aspects.

BACKGROUND: Coronavirus disease 2019 (COVID­19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is associated with a high level of mortality. OBJECTIVE: This updated review aims to present the most important traditional medicinal plants and some of their secondary metabolites that have previously and more recently been shown to affect viruses and may represent a beneficial contributory step against SARS-CoV-2 as the cause of COVID-19. Moreover, the mechanism aspects of these secondary metabolites were discussed, which may help find more reliable drugs against SARSCoV- 2. METHODS: Articles were searched on scientific websites including Google Scholar, Scopus, Web of Science, PubMed, and IranMedex using the search terms herbal medicine and traditional medicine with coronavirus, SARS-CoV-2, or COVID-19. Human, animal, and in vitro studies were identified in the search. RESULTS: Medicinal plants and their secondary metabolites may possess a potential role in combating this disease, and researchers suggest that some of these plants and their constituent compounds have inhibitory activity on coronaviruses. Numerous medicinal plants, their extracts, and secondary metabolites have been investigated over a period of time for antiviral activity. Among them, kaempferol, silybin, myricitrin, licoleafol, and curcumin are promising agents with potential activity against SARS-CoV-2. Natural compounds can form strong bonds with the active sites of SARS-CoV-2 protease. Structural and non-structural SARS-CoV-2 proteins such as Spike protein, PLpro, and 3CLpro are inhibited by these phytochemicals. CONCLUSION: Prospective treatments targeted at the life cycle stages of the virus may eventuate from research endeavors, and it must not be discounted that therapy originally derived from plant secondary metabolite sources may potentially have a part to play.

Biosynthesis of titanium dioxide nanoparticles using Hypericum perforatum and Origanum vulgare extracts and their main components, hypericin and carvacrol as promising antibacterial agents.

OBJECTIVE: To evaluate the anti-bacterial activities of titanium dioxide (TiO) nanoparticles of Origanum (O.) vulgare and Hypericum (H.) perforatum extracts, carvacrol and hypericin against Staphylococcus (S.) aureus. METHODS: In this study, TiOnanoparticles of O. vulgare and H. perforatum extracts, carvacrol and hypericin, were prepared and their antibacterial effects were evaluated against Staphylococcus (S.) aureus. In this study, scanning electron microscope, fourier transform infrared spectrometer, atomic force microscopy, dynamic light scattering and zeta potential were used to investigate the structure of synthesized drugs. RESULTS: Anti-bacterial activity of synthesized NPs was tested by minimum inhibitory concentration (MIC), minimum bactericidal concentration and disc diffusion method. MICs of TiO-NPs synthesized using O. vulgare, H. perforatum, carvacrol and hypericin and TiO were obtained 250, 62.5, 250, and 250, and 500 µg/mL, respectively. The MBCs for all of these were obtained 1000 µg/mL. CONCLUSION: Green-synthesized of TiO nanoparticles provides a promising approach to the use of O. vulgare and H. perforatum, carvacrol and hypericin as novel agents and safer antibacterial compounds, especially anti-S. aureus compounds.

Antiviral Compounds Based on Natural Astragalus polysaccharides (APS): Research and Foresight in the Strategies for Combating SARS-CoV-2 (COVID-19).

Today, finding natural polymers with desirable properties for use in various industries is one of the critical axes of research in the world. Polysaccharides are a group of natural polymers that have various applications in the pharmaceutical industry. The attachment of monosaccharides forms polysaccharides through glycosidic bonds that are widely found in various sources, including plants. Genus Astragalus belongs to the Fabaceae family. Plants belonging to this genus have different polysaccharides. Astragalus polysaccharides (APS) have attracted a great deal of attention among natural polymers because they are non-toxic, biodegradable, and biocompatible. Currently, APS have great drug potential for curing or treating various diseases. Due to the different biological activities of polysaccharides, including Astragalus, this study has investigated the chemical structure of APS, reporting on the antiviral and anti-inflammatory activities as well as stimulation of cytokine secretion by these polysaccharides. Also, in this study, the pharmaceutical approaches of APS compounds, as a natural, new and inexpensive source, have been discussed as suitable candidates for use in pharmaceutical formulations and preparation of new drugs to control COVID-19 infection.

Protective effect of Rheum ribes extract against lead-induced hepatotoxicity in male rats

Abstract The effects of Rheum ribes on lead acetate levels and hepatic biochemical factors due to lead acetate toxicity were investigated. Forty male Wistar rats were designated into four groups: Control; lead acetate (receiving in drinking water at 0.6 g/L, daily); hydroalcoholic extract groups (200 and 400 mg/kg doses, gavage, once daily). Treatments were conducted for 10 days. On the 11th day, blood samples were collected to measure lead acetate levels and biochemical factors. Liver tissue samples were examined for histopathological changes. Lead serum levels were increased in lead acetate-treated rats (p<0.001). Lead acetate treatment was associated with a significant increase in liver tissue damage (p<0.001), while R. ribes extract prevented liver tissue damage (p<0.05). The levels of alanine aminotransferase and aspartate aminotransferase were significantly lower in the groups lead acetate + extract (two doses) than in the lead acetate group (p<0.001 and P<0.01, respectively), but alkaline phosphatase level, prothrombin time, partial thromboplastin time and international normalized ratio were not different between the lead acetate + extract groups and the lead acetate group. The results showed the inhibitory role of R. ribes on lead-induced hepato-toxicity. The results make Rhubarb a good candidate to protect against the deleterious effect of chronic lead intoxication after complementary studies

Role of Lipid Accumulation and Inflammation in Atherosclerosis: Focus on Molecular and Cellular Mechanisms.

Atherosclerosis is a chronic lipid-driven and maladaptive inflammatory disease of arterial intima. It is characterized by the dysfunction of lipid homeostasis and signaling pathways that control the inflammation. This article reviews the role of inflammation and lipid accumulation, especially low-density lipoprotein (LDL), in the pathogenesis of atherosclerosis, with more emphasis on cellular mechanisms. Furthermore, this review will briefly highlight the role of medicinal plants, long non-coding RNA (lncRNA), and microRNAs in the pathophysiology, treatment, and prevention of atherosclerosis. Lipid homeostasis at various levels, including receptor-mediated uptake, synthesis, storage, metabolism, efflux, and its impairments are important for the development of atherosclerosis. The major source of cholesterol and lipid accumulation in the arterial wall is proatherogenic modified low-density lipoprotein (mLDL). Modified lipoproteins, such as oxidized low-density lipoprotein (ox-LDL) and LDL binding with proteoglycans of the extracellular matrix in the intima of blood vessels, cause aggregation of lipoprotein particles, endothelial damage, leukocyte recruitment, foam cell formation, and inflammation. Inflammation is the key contributor to atherosclerosis and participates in all phases of atherosclerosis. Also, several studies have shown that microRNAs and lncRNAs have appeared as key regulators of several physiological and pathophysiological processes in atherosclerosis, including regulation of HDL biogenesis, cholesterol efflux, lipid metabolism, regulating of smooth muscle proliferation, and controlling of inflammation. Thus, both lipid homeostasis and the inflammatory immune response are closely linked, and their cellular and molecular pathways interact with each other.

A Comparative Study on Anticancer Effects of the Alhagi maurorum and Amygdalus haussknechtii Extracts Alone and in Combination with Docetaxel on 4T1 Breast Cancer Cells.

Medicinal plants have long been studied due to their anticancer effects and use of them is commonly increased as a complementary and alternative medicine (CAM therapies) among patients with cancer. In this study, Alhagi maurorum (A.m) and Amygdalus haussknechtii (A.h) extracts were evaluated for their effects on inhibiting the growth of 4T1 breast cancer cells. Based on MTT assay results, the IC50s of A.m and A.h extracts were 57 µg/ml and 85 µg/ml, respectively. Then the cell migration, gene expression, and degree of apoptosis after 48 hours in each treated group with A.m and A.h extracts alone or in combination with docetaxel (DTX) on 4T1 cells were evaluated. A.m had a synergistic behavior with DTX (CI < 1). A.h reduced DTX IC50 but presented CI > 1. Cell migration assay showed that each extract alone or in combination with DTX prevented the migration of 4T1 cells. The Ao/EB staining and flowcytometry results confirmed that, in combination therapy, A.m + DTX and A.h + DTX induced apoptosis close to the level of DTX. Real-time PCR analysis showed that A.m + DTX (IC50 + IC25) downregulated the mRNA expression of HIF-1α and FZD7. A.m + DTX (IC50 + IC10) group decreased the expression of HIF-1α. Moreover, in A.h + DTX (IC50 + IC25) group, ß-Catenin and FZD7 were downregulated and upregulated, respectively. Generally, our findings suggest that the combination of A.m and DTX possesses synergistic antitumor effects on 4T1 cells, which may be a valuable choice for CAM therapies. A.h has an acceptable antitumor activity but not in combination with DTX.

Mechanistic Aspects of Medicinal Plants and Secondary Metabolites against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND AND OBJECTIVE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a highly pathogenic virus, is responsible for a respiratory disease termed coronavirus disease 2019 (COVID-19). SARS-CoV-2 genome encodes various structural and non-structural proteins, which are necessary for viral entry and replication. Among these proteins, papain-like protease (PLpro), 3C-like protease (3CLpro), RNAdependent RNA polymerase (RdRp), helicase, serine protease, and spike protein are potential targets of herbal remedies and phytocompounds for inhibition of viral infection and replication. There is, at present, no confirmed cure for the COVID-19. Various plants and their components have been introduced against SARS-CoV-2. A number of review articles have also been published on them. This article is focused on the mechanistic aspects of these plants and their derivatives on SARS-CoV-2. METHODS: The material in this review article was prepared from significant scientific databases, including Web of Science, PubMed, Science Direct, Scopus and Google Scholar. RESULTS: Different medicinal plants and their phytocompounds interact with important structural and nonstructural of SARS-CoV-2 proteins. Natural compounds form strong bonds with the active site of SARS-CoV-2 protease and make large conformational changes. These phytochemicals are potential inhibitors of structural and non-structural SARS-CoV-2 proteins such as Spike protein, PLpro, and 3CLpro. Some important anti- SARS-CoV-2 actions of medicinal plants and their metabolites are: inhibition of the virus replication or entry, blocking the angiotensin-converting enzyme 2 (ACE-2) receptor and "Transmembrane protease, serine 2 (TMPRSS2), regulation of inflammatory mediators, inhibition of endothelial activation, toll-like receptors (TLRs) and activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2). Some of these important natural immune boosters that are helpful for the prevention and cure of various symptoms related to COVID-19 include Allium sativum, Nigella sativa, Glycyrrhiza glabra Zingiber officinalis, Ocimum sanctum, Withania somnifera, Tinospora cordifolia, and Scutellaria baicalensis. Also, Kaempferol, Quercetin, Baicalin, Scutellarin, Glycyrrhizin, Curcumin, Apigenin, Ursolic acid, and Chloroquine are the best candidates for treating the symptoms associated with SARS-CoV-2 infection. CONCLUSION: Medicinal plants and/or their bioactive compounds with inhibitory effects against SARS-CoV-2 support the human immune system and help in fighting against COVID-19 and rejuvenating the immune system.

Up-regulation of chemokine receptor type 4 expression in the ischemic reperfused heart by alcoholic extract of Cichorium intybus rescue the heart from ischemia injury in male rat.

OBJECTIVES: Cichorium intybus is used in traditional medicine for various diseases including heart disease. This study aimed at evaluating the chemokine receptor type 4 up-regulation and cardioprotective effects of hydroalcoholic extract of C. intybus in a rat model of ischemic reperfusion. METHODS: Animals in four groups of eight rats each received vehicle or one of three doses of C. intybus (50, 100 or 200 mg/kg/d) for 14 days. Then they were subjected to 30 min of ischemia followed by 7 days of reperfusion. At the end of the experiment, blood specimens were prepared for serum assays. The level of myocardium chemokine receptor type 4 was also measured using RT-PCR. KEY FINDINGS: Cichorium intybus (CI-50) improved infarct size, episodes of the ventricular ectopic beat, ventricular tachycardia, and duration of ventricular tachycardia, QTc shortening. It also stabilized the ST segment changes and increased heart rate during ischemia. The blood pressure decreased in CI-50 group in comparison to the control and CI-200 group. C. intybus increased serum superoxide dismutase and reduced lactate dehydrogenase activity, Cardiac Troponin I and malondialdehyde levels. C. intybus led to an increase in the expression of chemokine receptor type 4. CONCLUSIONS: These findings suggest that C. intybus administration before ischemia is able to induce cardioprotective effect against ischemic reperfusion injury, probably through chemokine receptor type 4 over-expression and antioxidant activity.

The Roles of Vitamin D in Increasing the Body's Immunity and Reducing Injuries due to Viral Infections: With an Emphasis on its Possible Role in SARS-CoV-2 (COVID-19).

BACKGROUND: It is known that vitamin D can increase the body's immunity against some viral infections. Many people worldwide have vitamin D deficiency; therefore, this has become a public concern whether vitamin D is an important factor protecting against COVID-19 infection. In this paper, the data about the roles of vitamin D in immunity and recovery from viral infections, especially novel Coronavirus disease (COVID- 19), are reviewed. METHODS: The electronic databases of Pubmed, Google Scholar, Research Gate, Excerpta Media Database (EMBASE), and Medical and Health Education (Medrix) were searched. RESULTS: Vitamin D is considered an important factor in immune homeostasis. Various effects have been considered for this nutrient on the immune system, particularly because of vitamin D receptor (VDR) and Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) expression in most of the immune cells. Vitamin D can increase cellular immunity, reduce cytokine storm, and enhance antioxidants production. It also has modulatory effects on Angiotensin-converting enzyme 2 (ACE2) receptors and might have protective functions against acute lung injuries, including COVID-19 infection. However, there are some articles against this positive effect. CONCLUSION: Vitamin D supplementation is reported to be effective in the enhancement of the immune system and might be effective in the treatment and prevention of COVID-19 infection, especially in those with its deficiency. However, it should be considered that vitamin D deficiency shows the overall health status of the patients and cannot be considered specific for COVID-19 infection.

Effect of fennel on primary dysmenorrhea: a systematic review and meta-analysis.

BACKGROUND: One of the most common complaints for women is dysmenorrhea. Several studies investigated the treatment effects of medicinal plants on primary dysmenorrhea. OBJECTIVES: This systematic review and meta-analysis investigates the effect of Foeniculum vulgare (Fennel) on pain in primary dysmenorrhea in comparison to non-steroidal anti-inflammatory drugs such as mefenamic acid. METHODS: PubMed, EMBASE, EBSCO Web of Science, Scopus, Cochrane library, Cochrane Central Register of Controlled Trials (CENTRAL), Science Direct, ProQuest, ISI Web of Science, Google Scholar, Magiran, SID, Iran Medex, and Irandoc were searched up to January 2019. Quality assessment of clinical trials was conducted using Jadad scoring system. Totally, 12 studies were entered in the meta-analysis. I 2 was calculated to determine heterogeneity. Fixed effects and/or random effects models were applied. RESULTS: Meta-analysis of these trials showed that F. vulgare intake decreased significantly the intensity of dysmenorrhea compared to the placebo (SMD -0.632; CI: -0.827 to -0.436; p<0.001; heterogeneity p=0.807; I 2=0%; fixed effect model; seven articles). However, the effect of Mefenamic acid with F. vulgare was not different from each other (SMD=-0.214; CI: -0.446 to 0.017; p=0.07; heterogeneity p=0.58; I 2=0%; fixed effect model; six trials). CONCLUSION: The F. vulgare alleviates dysmenorrhea. Regarding the same effect of F. vulgare with NSAIDs, it is highly recommend to the women suffered from dysmenorrhea specifically the ones who have high tendency toward herbal medicine.

Phytotherapy for Wound Healing: The Most Important Herbal Plants in Wound Healing Based on Iranian Ethnobotanical Documents.

Wound healing is a process that starts with the inflammatory response after the occurrence of any damage. This process initiates by restoring the wound surface coating tissue, migrating fibroblasts to form the required collagen, forming a healing tissue and finally, leading to contortion and extraction of the wound. Today, various drugs are used to heal wounds. However, the drugs used to repair wounds have some defects and side effects. In spite of all attempts to accelerate wound healing definitely, no safe drug has been introduced for this purpose. Therefore, the necessity to identify herbal plants in ethnopharmacology and ethnobotany documents with healing effects is essential. In this article, we tried to review and present effective Iranian medicinal plants and herbal compounds used for wound healing. Searching was performed on databases, including ISI Web of Science, PubMed, PubMed Central, Scopus, ISC, SID, Magiran and some other databases. The keywords used included wound healing, skin treatment, medicinal plants, ethnobotany, and phytotherapy. In this regard, 139 medicinal plants effective on wound healing were identified based on ethnopharmacology and ethnobotanical sources of Iran. Plants such as Salvia officinalis, Echium amoenum, Verbascum spp., G1ycyrrhiza glabra, Medicago sativa, Mentha pulegium, Datura stramonium L., Alhagi spp., Aloe vera, Hypericum perforatum, Pistacia atlantica and Prosopis cineraria are the most important and useful medicinal plants used for wound healing in Iran. These native Iranian medicinal plants are rich in antioxidants and biological compounds and might be used for wound healing and preparation of new drugs.

Effect of Curcuma zedoaria hydro-alcoholic extract on learning, memory deficits and oxidative damage of brain tissue following seizures induced by pentylenetetrazole in rat.

BACKGROUND: Previous studies have shown that seizures can cause cognitive disorders. On the other hand, the Curcuma zedoaria (CZ) has beneficial effects on the nervous system. However, there is little information on the possible effects of the CZ extract on seizures. The aim of this study was to investigate the possible effects of CZ extract on cognitive impairment and oxidative stress induced by epilepsy in rats. METHODS: Rats were randomly divided into different groups. In all rats (except the sham group), kindling was performed by intraperitoneal injection of pentylenetetrazol (PTZ) at a dose of 35 mg/kg every 48 h for 14 days. Positive group received 2 mg/kg diazepam + PTZ; treatment groups received 100, 200 or 400 mg/kg CZ extract + PTZ; and one group received 0.5 mg/kg flumazenil and CZ extract + PTZ. Shuttle box and Morris Water Maze tests were used to measure memory and learning. On the last day of treatments PTZ injection was at dose of 60 mg/kg, tonic seizure threshold and mortality rate were recorded in each group. After deep anesthesia, blood was drawn from the rats' hearts and the hippocampus of all rats was removed. RESULTS: Statistical analysis of the data showed that the CZ extract significantly increased the tonic seizure threshold and reduced the pentylenetetrazol-induced mortality and the extract dose of 400 mg/kg was selected as the most effective dose compared to the other doses. It was also found that flumazenil (a GABAA receptor antagonist) reduced the tonic seizure threshold compared to the effective dose of the extract. The results of shuttle box and Morris water maze behavioral tests showed that memory and learning decreased in the negative control group and the CZ extract treatment improved memory and learning in rats. The CZ extract also increased antioxidant capacity, decreased MDA and NO in the brain and serum of pre-treated groups in compared to the negative control group. CONCLUSION: It is concluded that the CZ extract has beneficial effects on learning and memory impairment in PTZ-induced epilepsy model, which has been associated with antioxidant effects in the brain or possibly exerts its effects through the GABAergic system.

Hydroalcoholic Extract of Anchusa Italica Protects Global Cerebral Ischemia-Reperfusion Injury Via a Nitrergic Mechanism.

INTRODUCTION: In stroke models, Inducible Nitric Oxide Synthase (iNOS) expression initiates cellular toxicity due to excessive Nitric Oxide (NO) generation. Anchusa italica is a medicinal herb with anti-inflammatory, antioxidant and neuroprotective properties. This study evaluated the antioxidant activity and NOS mRNA expression of the Hydroalcoholic Extract Of Anchusa Italica (HEAI) in an experimental stroke model in rats. METHODS: The stroke model was induced by bilateral occlusion of both common carotid arteries for 60 min. Twenty-four hours after surgery, HEAI (50 and 100 mg/kg i.p.) was injected daily for 10 consecutive days. mRNA expression levels of NOS subtypes and hippocampal Brain-Derived Neurotrophic Factor (BDNF) were studied using real-time PCR. Besides, hippocampal tissue plus serum concentrations of NO and Malondialdehyde (MDA) were measured. RESULTS: HEAI decreased MDA in both serum and hippocampal tissue and also reduced serum NO levels. Additionally, in the HEAI-treated groups, a down-regulation of iNOS mRNA expression, and an up-regulation of BDNF mRNA expression were observed. CONCLUSION: The results indicated that the administration of HEAI even after the onset of ischemia protects the brain from free radical injury and inflammation via a down-regulation of iNOS expression inhibiting NO production and an up-regulation of BDNF mRNA.

Mechanisms of Medicinal Plant Activity on Nitric Oxide (NO) Bioavailability as Prospective Treatments for Atherosclerosis.

BACKGROUND AND OBJECTIVE: Atherosclerosis is one of the leading causes of human morbidity globally and reduced bioavailability of vascular nitric oxide (NO) has a critical role in the progression and development of the atherosclerotic disease. Loss of NO bioavailability, for example via a deficiency of the substrate (L-arginine) or cofactors for endothelial nitric oxide synthase (eNOS), invariably leads to detrimental vascular effects such as impaired endothelial function and increased smooth muscle cell proliferation, deficiency of the substrate (Larginine) or cofactors for eNOS. Various medicinal plants and their bioactive compounds or secondary metabolites with fewer side effects are potentially implicated in preventing cardiovascular disease by increasing NO bioavailability, thereby ameliorating endothelial dysfunction. In this review, we describe the most notable medicinal plants and their bioactive compounds that may be appropriate for enhancing NO bioavailability, and treatment of atherosclerosis. METHODS: The material in this article was obtained from noteworthy scientific databases, including Web of Science, PubMed, Science Direct, Scopus and Google Scholar. RESULTS: Medicinal plants and their bioactive compounds influence NO production through diverse mechanisms including the activation of the nuclear factor kappa B (NF-κB) signaling pathway, activating protein kinase C (PKC)-α, stimulating protein tyrosine kinase (PTK), reducing the conversion of nitrite to NO via nitrate-nitrite reduction pathways, induction of eNOS, activating the phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase B (AKT) (PI3K/AKT/eNOS/NO) pathway and decreasing oxidative stress. CONCLUSION: Medicinal plants and/or their constituent bioactive compounds may be considered as safe therapeutic options for enhancing NO bioavailability and prospective preventative therapy for atherosclerosis.

Campylobacter: A Review of New Promising Remedies with Medicinal Plants and Natural Antioxidants.

Campylobacter (curved bacteria) is considered one of the most important and common zoonotic bacteria and the three leading bacterial causes of gastroenteritis and diarrhea. Antibacterial resistance is growing and expanding. The aim of this review article is to report anti-Campylobacter medicinal plants. For this purpose, the search terms consisting of Campylobacter, medicinal plants, essential oil, extract, and traditional medicine were used to retrieve the relevant articles published in the journals indexed in Information Sciences Institute, Web of Science, PubMed, Scopus, Google Scholar, and Scientific Information Databases. Then, the findings of eligible articles were analyzed. According to the analysis, 71 medicinal plants were found to exert anti-Campylobacter effect. The active compounds of these plants are possibly nature-based antibiotic agents that are effective on Campylobacter. If these compounds are isolated, purified, and studied in pharmaceutical investigations, they can be used to produce nature-based, anti-Campylobacter antibiotics.

Review of Phytochemical Compounds as Antiviral Agents Against Arboviruses from the Genera Flavivirus and Alphavirus.

Arboviruses are a diverse group of viruses that are among the major causes of emerging infectious diseases. Arboviruses from the genera flavivirus and alphavirus are the most important human arboviruses from a public health perspective. During recent decades, these viruses have been responsible for millions of infections and deaths around the world. Over the past few years, several investigations have been carried out to identify antiviral agents to treat these arbovirus infections. The use of synthetic antiviral compounds is often unsatisfactory since they may raise the risk of viral mutation; they are costly and possess either side effects or toxicity. One attractive strategy is the use of plants as promising sources of novel antiviral compounds that present significant inhibitory effects on these viruses. In this review, we describe advances in the exploitation of compounds and extracts from natural sources that target the vital proteins and enzymes involved in arbovirus replication.

Effective Antiviral Medicinal Plants and Biological Compounds Against Central Nervous System Infections: A Mechanistic Review.

BACKGROUND AND OBJECTIVE: Infectious diseases are amongst the leading causes of death in the world and central nervous system infections produced by viruses may either be fatal or generate a wide range of symptoms that affect global human health. Most antiviral plants contain active phytoconstituents such as alkaloids, flavonoids, and polyphenols, some of which play an important antiviral role. Herein, we present a background to viral central nervous system (CNS) infections, followed by a review of medicinal plants and bioactive compounds that are effective against viral pathogens in CNS infections. METHODS: A comprehensive literature search was conducted on scientific databases including: PubMed, Scopus, Google Scholar, and Web of Science. The relevant keywords used as search terms were: "myelitis", "encephalitis", "meningitis", "meningoencephalitis", "encephalomyelitis", "central nervous system", "brain", "spinal cord", "infection", "virus", "medicinal plants", and "biological compounds". RESULTS: The most significant viruses involved in central nervous system infections are: Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), West Nile Virus (WNV), Enterovirus 71 (EV71), Japanese Encephalitis Virus (JEV), and Dengue Virus (DENV). The inhibitory activity of medicinal plants against CNS viruses is mostly active through prevention of viral binding to cell membranes, blocking viral genome replication, prevention of viral protein expression, scavenging reactive Oxygen Species (ROS), and reduction of plaque formation. CONCLUSION: Due to the increased resistance of microorganisms (bacteria, viruses, and parasites) to antimicrobial therapies, alternative treatments, especially using plant sources and their bioactive constituents, appear to be more fruitful.