Inhibition of TLR4, NF-κB, and INOS pathways mediates ameliorative effect of syringic acid in experimental ulcerative colitis in rats.

OBJECTIVE: Numerous therapeutics and pharmacological properties have been reported in syringic acid (SA). In this study, we aimed to evaluate effect of SA in ulcerative colitis (UC) in rats considering effect on TLR4, NF-κB, and INOS pathways. MATERIALS AND METHODS: 48 Wistar rats were randomly designated into six groups (n = 8). UC was induced via intra-rectal administration of 7% acetic acid (0.8 ml). SA at doses of 10, 25, 50 mg/kg was administrated through gavage, and dexamethasone (2 mg/kg) administrated intra-peritoneally for 5 consecutive days. The macroscopic and histopathological damages as well as expression of inflammatory and apoptotic genes along with superoxide dismutase (SOD) and catalase (CAT) activities, total antioxidant capacity (TAC), nitric oxide (NO), and malondialdehyde (MDA) levels in the colon tissue were assessed. RESULTS: UC led to an increase in the apoptotic and inflammatory genes, NO and MDA levels as well as decrease in TAC level, and SOD and CAT activities (p < 0.05). UC also caused severe damage, edema, inflammation, and necrosis in the colon. SA significantly reduced gene expressions of INOS, TLR4, IL-6, IL-1ß, NF-κB, Caspase-3, Caspase-8, and Bax. SA ameliorated negative macroscopic and histopathologic effects of UC. SA significantly reduced MDA and NO levels, and increased TAC level and CAT activity in the colon tissue in comparison to the UC rats without treatment (p < 0.05). CONCLUSION: SA via attenuation of the TLR4-NF-κB, NF-κB-INOS-NO pathways, oxidative stress, inflammation, and apoptosis of UC in rats.

Ferulic acid ameliorates ulcerative colitis in a rat model via the inhibition of two LPS-TLR4-NF-κB and NF-κB-INOS-NO signaling pathways and thus alleviating the inflammatory, oxidative and apoptotic conditions in the colon tissue.

INTRODUCTION: Ulcerative colitis is a chronic inflammation of the colon. However, the common treatment for it is accompanied by many complications. Therefore, the present study was aimed to determine the ameliorative effects of ferulic acid on acetic acid-induced colitis in rat. MATERIALS AND METHODS: To induce ulcerative colitis, animals received 0.8 ml of 7% acetic acid intra-rectally. Ferulic acid in 20, 40, and 60 mg/kg doses was administered orally one hour after the ulcerative colitis induction. Animals received treatments for five consecutive days and then were euthanized on the sixth day. The colon was dissected out and macroscopic lesions were examined. Colon samples were evaluated for histopathological examination, biochemical analysis, determination of the expression of inflammatory, and apoptotic genes as well as total antioxidant capacity. RESULTS: Ferulic acid significantly inhibited inflammatory and apoptotic genes mRNA expression, also production of MDA and NO. Ferulic acid significantly increased the activity of antioxidant factors (TAC content, and SOD and CAT activity), thereby preventing inflammation and histopathological damage in the colon tissue of colitis rats. CONCLUSION: The results of the present study confirmed the antioxidant, anti-inflammatory, and anti-apoptotic properties of ferulic acid. About the mechanism of action of this compound, it can be concluded that the ability of ferulic acid in the amelioration of ulcerative colitis is related to the inhibition of two LPS-TLR4-NF-κB and NF-κB-INOS-NO signaling pathways.

Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo.

Breast cancer is a challenging disease and leading cause of cancer death in women. There is no effective agent for metastatic breast cancer after surgery and chemotherapy. Alhagi maurorum (A.m) has been reported to exhibit an anticancer effect on various types of cancer cells in vitro. This study aimed to examine the suppressive effect of A.m alone and combined with docetaxel (DTX) on the breast cancer growth in mice models and the possible underlying mechanisms. In the present study, the mice were inoculated subcutaneously with the injections of 4T1 cells. Then, A.m, DTX, and their combination were administered intraperitoneally. The expressions of ß-catenin (ß-cat), FZD7, MMP2, HIF1-α, and VEGF A (vascular endothelial growth factor A) were investigated using RT-PCR method. Also, plasma alkaline phosphatase (ALP), alanine aminotransferase (GPT or ALT), aspartate transaminase (GOT or AST), serum creatinine, and urea were examined, and histological analyses of the tissues were conducted. The results demonstrated that A.m (500 mg/kg) combined with DTX significantly decreased the expression of ß-cat, MMP2, and FZD7 as compared with the negative control group and monotherapies. Also, the mRNA levels of HIF1-α and VEGF A were suppressed significantly by DTX + A.m (500 mg/kg). Tumor weights and sizes were significantly lower and tumor inhibition rate was significantly higher in the DTX + A.m group. The A.m 500 mg/kg + DTX also suppressed the serum GPT level in tumor-bearing mice and decreased the serum urea level. Taken together, our findings suggest that DTX combined with A.m at an optimal dose of 500 mg/kg as the optimal dose can inhibit ß-cat, FZD7, MMP2, and breast cancer growth via interrupting HIF-1α/VEGF signaling and might be used as a promising antiangiogenic agent for breast cancer treatment.

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.

A review on garlic as a supplement for Alzheimer's disease: a mechanistic insight in its direct and indirect effects.

Alzheimer's disease (AD) is one of the most complicated neurodegenerative diseases causing dementia in human beings. Aside from that incidence of AD is increasing also its treatment is very complicated. There are several known hypotheses regarding the pathology of Alzheimer's disease, including the Amyloid beta hypothesis, Tau hypothesis, inflammation hypothesis, and cholinergic hypothesis, which are investigated in different researches to completely elucidate the pathology of AD. Aside from these some new mechanisms such as immune, endocrine, and vagus pathways, as well as bacteria metabolite secretions are being explained as other causes that are somehow related to AD pathogenesis. There is still no definite treatment for Alzheimer's disease that can completely cure and eradicate AD. Garlic (Allium sativum) is a traditional herb used as a spice in different cultures and due to the organosulfur compounds like allicin it possesses highly anti-oxidant properties and the benefits of garlic in cardiovascular diseases like hypertension and atherosclerosis is examined and reviewed, although its beneficiary effects in neurodegenerative diseases such as AD is not completely understood. In this review, we discuss the effects of garlic based on its components such as allicin, S-allyl cysteine on Alzheimer's disease and the mechanisms that garlic components can be beneficiary for AD patients, including its effects amyloid beta, oxidative stress, tau protein, gene expression, and cholinesterase enzymes. Based on the literature review we have done, garlic has revealed beneficiary effects on Alzheimer's disease, especially in animal studies; however, more studies should be done on human populations to find the exact mechanism of garlic effects on AD patients.

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.

Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19.

Natural resources have long played a prominent part in conventional treatments as a parental source due to their multifaceted functions and lesser side effects. The diversity of marine products is a significant source of possible bioactive chemical compounds with a wide range of potential medicinal applications. Marine organisms produce natural compounds and new drugs with unique properties are produced from these compounds. A lot of bioactive compounds with medicinal properties are extracted from marine invertebrates, including Peptides, Alkaloids, Terpenoids, Steroids. Thus, it can be concluded that marine ecosystems are endowed with natural resources that have a wide range of medicinal properties, and it is important to examine the therapeutic and pharmacological capabilities of these molecules. So, finding particular inhibitors of the COVID-19 in natural compounds will be extremely important. Natural ingredients, in this light, could be a valuable resource in the progression of COVID-19 therapeutic options. Controlling the immunological response in COVID-19 patients may be possible by addressing the PI3K/Akt pathway and regulating T cell responses. T cell effector activity can be improved by preventing anti-viral exhaustion by suppressing PI3K and Akt during the early anti-viral response. The diversity of marine life is a significant supply of potentially bioactive chemical compounds with a broad range of medicinal uses. In this study, some biologically active compounds from marine organisms capable of inhibiting PI3K/AKT and the possible therapeutic targets from these compounds in viral infection COVID-19 have been addressed.

Effects of Satureja Bachtiarica Essential Oil in Preventing Seizure in Pentylenetetrazol-Kindled Mice.

Introduction: Epilepsy is a group of chronic neurological disorders characterized by seizures. The present study aimed to investigate the effects of Satureja bachtiarica essential oil in preventing epilepsy. Methods: In this experimental study, 50 mice were randomly assigned to five groups of 10 each. The control group received normal saline plus tween-80 and after 30 min pentylenetetrazol (PTZ). Groups 2 and 3 were treated first with S. bachtiarica essential oil at 50 and 100 mg/kg, respectively and then after 30 min received PTZ. Group 4 received diazepam and 30 min later PTZ. Group 5 received flumazenil and 30 min later PTZ. After the last injection of PTZ, the time of seizure onset, seizure severity and score, the completion time of each seizure (attack episode), and mortality rate in different groups were recorded and compared. Results: The administration of S. bachtiarica essential oil at 50 and 100 mg/kg to PTZ-treated mice caused a significant increase in latency to the first seizure and survival of mice, as well as a significant decrease in the frequency of the head and upper limbs seizure, total body seizures, tonic seizures, and jumping. S. bachtiarica essential oil at 100 mg/kg caused a significant decrease in the head tic frequency. The administration of flumazenil significantly inhibited S. bachtiarica essential oil-induced effects and increased the head and upper limbs seizures, tonic seizures, and jumping. Conclusion: The present study demonstrated that S. bachtiarica essential oil could prevent PTZ-induced seizure and these findings authenticate the traditional claims about the use of S. bachtiarica in treating epilepsy. Highlights: The administration of S. bachtiarica essential oil at 50 and 100 mg/kg to pentylenetetrazol PTZ-treated mice caused a significant increase in latency to the first seizure.• The administration of S. bachtiarica essential oil at 50 and 100 mg/kg to PTZ-treated mice caused a significant decrease in the frequency of the head and upper limbs seizures, total body seizures, tonic seizures, and spin and jump.• The administration of flumazenil significantly inhibited S. bachtiarica essential oil-induced effects and increased the head and upper limbs seizures, tonic seizures, and jumping. Plain Language Summary: Epilepsy is one of the most common disorders of the central nervous system, so that one in every 100 people is suffering from epilepsy globally. Despite the development of antiepileptic drugs, novel strategies are sought out because of drug resistance and the side effects resulting from these drugs at high concentrations. Researchers have focused on plants for certain reasons such as availability, the history of long-term use, being nature-based, and relative safety. In the current study, the effect of the pretreatment with S. bachtiarica essential oil in preventing seizure was studied in the pentylenetetrazol-kindled mice. The injection of 50 and 100 mg/kg of S. bachtiarica essential oil caused a significant increase in latency to the first seizure and survival duration, and a significant decrease in the frequency of the head and upper limbs seizures, tonic seizures, and spin and jump in the pentylenetetrazol-receiving mice.

Gas Chromatography-Mass Spectrometry Analysis of Anbarnesa Smoke and Its Antiviral Activity.

Background: Anbarnesa is the female donkey dung typically collected after the labor and in early springtime. Materials and Methods: The chemical composition of the smoke collected from Anbarnesa was evaluated by gas chromatography-mass spectrometry (GC/MS), and its antiviral activity was analyzed based on 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Results: As a result, twenty-two constituents representing 97.1% of the Anbarnesa smoke could be identified. Hexadecanoic acid (29.4%), cis-9-octadecenoic acid (17.7%), and octadecanoic acid (10.8%) were the smoke's main constituents, respectively. Antiviral activity was evaluated using MTT assay. The CC50 value of the compound on Hep2 and Verro cells was 2271.2 µg/mL and 5077.5 µg/mL, respectively. Furthermore, the 50% inhibitory concentration value on adenovirus and herpes simplex type-1 was 802.55 µg/mL and >5077.5, respectively. Conclusions: it was revealed that Anbarnesa was nontoxic in 1/64, 1/128, and 1/256 dilutions, while the toxicity was detected in 1/32 dilution after 72 h. In addition, in 1/8 and 1/16 dilutions, cell toxicity was identified in the first hour.

In silico design of a multi-epitope vaccine against HPV16/18.

BACKGROUND: Cervical cancer is the fourth most common cancer affecting women and is caused by human Papillomavirus (HPV) infections that are sexually transmitted. There are currently commercially available prophylactic vaccines that have been shown to protect vaccinated individuals against HPV infections, however, these vaccines have no therapeutic effects for those who are previously infected with the virus. The current study's aim was to use immunoinformatics to develop a multi-epitope vaccine with therapeutic potential against cervical cancer. RESULTS: In this study, T-cell epitopes from E5 and E7 proteins of HPV16/18 were predicted. These epitopes were evaluated and chosen based on their antigenicity, allergenicity, toxicity, and induction of IFN-γ production (only in helper T lymphocytes). Then, the selected epitopes were sequentially linked by appropriate linkers. In addition, a C-terminal fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) was used as an adjuvant for the vaccine construct. The physicochemical parameters of the vaccine construct were acceptable. Furthermore, the vaccine was soluble, highly antigenic, and non-allergenic. The vaccine's 3D model was predicted, and the structural improvement after refinement was confirmed using the Ramachandran plot and ProSA-web. The vaccine's B-cell epitopes were predicted. Molecular docking analysis showed that the vaccine's refined 3D model had a strong interaction with the Toll-like receptor 4. The structural stability of the vaccine construct was confirmed by molecular dynamics simulation. Codon adaptation was performed in order to achieve efficient vaccine expression in Escherichia coli strain K12 (E. coli). Subsequently, in silico cloning of the multi-epitope vaccine was conducted into pET-28a ( +) expression vector. CONCLUSIONS: According to the results of bioinformatics analyses, the multi-epitope vaccine is structurally stable, as well as a non-allergic and non-toxic antigen. However, in vitro and in vivo studies are needed to validate the vaccine's efficacy and safety. If satisfactory results are obtained from in vitro and in vivo studies, the vaccine designed in this study may be effective as a therapeutic vaccine against cervical cancer.

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.

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

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.

Design of a multi-epitope vaccine against cervical cancer using immunoinformatics approaches.

Cervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. In this study, the E6 and E7 oncoproteins from HPV16 were chosen as the target antigens for epitope prediction. Cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) epitopes were predicted, and the best epitopes were selected based on antigenicity, allergenicity, and toxicity. The final vaccine construct was composed of the selected epitopes, along with the appropriate adjuvant and linkers. The multi-epitope vaccine was evaluated in terms of physicochemical properties, antigenicity, and allergenicity. The tertiary structure of the vaccine construct was predicted. Furthermore, several analyses were also carried out, including molecular docking, molecular dynamics (MD) simulation, and in silico cloning of the vaccine construct. The results showed that the final proposed vaccine could be considered an effective therapeutic vaccine for HPV; however, in vitro and in vivo experiments are required to validate the efficacy of this vaccine candidate.

Effect of White Tea (Camellia sinensis) Extract on Skin Wound Healing Process in Rats.

BACKGROUND: White tea (Camellia sinensis) has anti-inflammatory and antioxidant properties and a protective effect against wrinkles, sunburn and UV damages on the skin. Thus, we aimed to evaluate the effect of white tea extract on the healing process of skin wounds in rats. METHODS: This study was done in the Research Center of Shahrekord University of Medical Sciences, Shahrekord, Iran in 2019. Excisional skin wounds were created on five groups of healthy male Wistar rats (200-250 g, n=21) including control group, Eucerin-treated group, white tea 5% ointment (Eucerin) treated group, gel-treated group, white tea 5% gel treated group. Treatment was begun on day 1 and repeated every day at the same time until day 15. Pathologic samples were taken on days 4, 7 and 15 for histopathological examinations. Kruskal-Wallis test was used to analyze data by SPSS. Statistical significance was defined as P<0.05. RESULTS: Wound closure rate of control group was more than other groups on day 4 (P<0.05). On day 7, reepithelisation and granulation tissue of control group were more than white tea 5% ointment-treated and its inflammation was less than others (P<0.05). Neo-vascularization of white tea 5% ointment-treated group was more than control group on days 4 and 15 (P<0.05). On day 4, intact mast cells of control group were more than white tea treated groups (P<0.05). Degranulated mast cells of white tea 5% gel treated group was significantly (P<0.05) more than control group on days 4 and 15. CONCLUSION: Five percent white tea extract could not help the skin wound healing process.

Phytochemical Investigation on Volatile Compositions and Methoxylated Flavonoids of Agrostis gigantea Roth.

In this study, methoxylated flavonoids and volatile constitutions of Agrostis gigantea Roth (Poaceae) were investigated for the first time. The flavonoids were identified by spectroscopic methods (1H-NMR, 13C-NMR, COSY, NOSEY, TCOSY, and HMBC). The volatile constitutions of aerial parts and seeds were analyzed by gas chromatography-mass spectrometry (GC-MS). Two methoxylated flavonoids, luteolin 5-methyl ether (1), and cirsilineol (2) were isolated from the aerial parts of this plant. According to the GC-MS data the main constitutions of these volatile oils belong to the simple phenolic category which include coniferyl alcohol (18.80%) and eugenol (12.19%) in aerial parts and seeds, respectively. By using the computer- aided molecular modeling approaches, the binding affinity of these compounds was predicted in the catalytic domains of aryl hydrocarbon receptor (AhR). These two isolated flavonoids were investigated in-vitro for their inhibitory activity on 4T1 breast carcinoma cells. It was predicted that these compounds could be well-matched in aryl hydrocarbon receptor (3H82) active site, but based on the in-vitro assay, the IC50 values on cytotoxicity were 428.24 ±3.21 and 412.7±3.02 µg/mL for luteolin 5-methyl ether and cirsilineol, respectively. Thus, it can be concluded that these flavonoids exhibit low cytotoxicity against 4T1 breast carcinoma cell line.

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.

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.

Impact of glazing based on chitosan-gelatin incorporated with Persian lime (Citrus latifolia) peel essential oil on quality of rainbow trout fillets stored at superchilled condition.

In this research, a new ice-glazing based on chitosan-gelatin (Ch-Gl) incorporated with Persian lime peel essential oil (LEO), and superchilled storage was established to assess the microbial, physicochemical, and sensory quality of rainbow trout fillets. The fillets were immersed in distilled water (control), Ch-Gl, Ch-Gl + 1% LEO, and Ch-Gl + 2% LEO to form glazing layer on the surface, then stored at -1.4 °C for 30 days. All treatments delayed the growth of total mesophilic bacteria, total psychrotrophic bacteria, Enterobacteriaceae, and lactic acid bacteria compared to control during the storage period. The treatments also retarded the increase in the contents of total volatile nitrogen, conjugated dienes, thiobarbituric acid reactive substances, protein carbonyls, pH, and electric conductivity during storage. The freshness indexes i.e. K and Fr values were improved in treated groups compared to control group. The combined treatments (Ch-Gl + 1% or 2% LEO) were more effective than Ch-Gl alone to inhibit the microbial growth, retard the physicochemical deterioration, and improve freshness indexes in the fillets. It can be concluded that ice-glazing based on Ch-Gl incorporated with LEO, and superchilled storage is effective to enhance the quality and shelf-life of rainbow trout fillets.