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Garlic is an important bulb vegetable because of its medicinal and nutritional values. Selenium, an important trace element, and humic acid, a soil amendment, can positively affect garlic's nutritional values. To evaluate the impact of selenium and humic acid on antioxidant activity and phenol, flavonoid and allicin contents in garlic, Na2SeO4solution was sprayed in concentrations of 0, 10, 20 and 30 μg Se/mL, and humic acid was used in fertigation at rates of 0, 10 and 20 kg/ha. Results showed the applied treatments had positive effects on the total antioxidant activity in garlic. The application of low concentrations of Se with moderate amounts of humic acid caused the highest antioxidant activity, as did the application of high Se concentrations with no humic acid. Humic acid at the rate of 10 kg/ha contributed more to the lower total phenol content than did the 20 kg/ha (H20) rate. The Se treatment decreased flavonoid content, and the control plants (Se0) had the highest amount of flavonoids. The results regarding sulphur and allicin contents were greatly similar in that they were both at their maximum level in the Se0H20treatment. Se0led to the highest allicin content, and its difference from other Se treatments was significant (P< 0.01). A strong negative correlation was found between selenium concentration and allicin content (R2= 0.881). The findings showed that humic acid positively affects most tested traits, but negative or no effects were seen for the Se treatment. Therefore, if the production of Se-enriched garlic is the aim, a decrease in some nutritional values must be accepted. [ABSTRACT FROM AUTHOR]

Melanoma is responsible for most skin cancer-associated deaths globally. The progression of melanoma is influenced by a number of pathogenic processes. Understanding the VEGF/VEGFR axis, which includes VEGF-A, PlGF, VEGF-B, VEGF-C, and VEGF-D and their receptors, VEGFR-1, VEGFR-2, and VEGFR-3, is of great importance in melanoma due to its crucial role in angiogenesis. This axis generates multifactorial and complex cellular signaling, engaging the MAPK/ERK, PI3K/AKT, PKC, PLC-γ, and FAK signaling pathways. Melanoma cell growth and proliferation, migration and metastasis, survival, and acquired resistance to therapy are influenced by this axis. The VEGF/VEGFR axis was extensively examined for their potential as diagnostic/prognostic biomarkers in melanoma patients and results showed that VEGF overexpression can be associated with unfavorable prognosis, higher level of tumor invasion and poor response to therapy. MicroRNAs linking to the VEGF/VEGFR axis were identified and, in this review, divided into two categories according to their functions, some of them promote melanoma angiogenesis (promotive group) and some restrict melanoma angiogenesis (protective group). In addition, the approach of treating melanoma by targeting the VEGF/VEGFR axis has garnered significant interest among researchers. These agents can be divided into two main groups: anti-VEGF and VEGFR inhibitors. These therapeutic options may be a prominent step along with the modern targeting and immune therapies for better coverage of pathological processes leading to melanoma progression and therapy resistance., Competing Interests: Declaration of competing interest There is no actual and potential conflict of interest between authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Phenolic acids have recently gained considerable attention because of their numerous practical, biological, and pharmacological benefits. Various polyphenolic compounds are widely distributed in plant sources. Flavonoids and phenolic acids are the two main polyphenolic compounds that many plants contain abundant polyphenols. Chlorogenic acid, one of the most abundant phenolic acids, has various biological activities, but it is chemically unstable and degrades into other compounds or different enzymatic processes., Methods: In this review, we have studied many publications about CA and its derivatives. CA derivatives were classified into three categories in terms of structure and determined each part's effects on the body. The biological evaluations, structure-activity relationship, and mechanism of action of CA derivatives were investigated. The search databases for this review were ScienceDirect, Scopus, Pub- Med and google scholar., Results: Many studies have reported that CA derivatives have demonstrated several biological effects, including anti-oxidant, anti-inflammatory, anti-microbes, anti-mutation, anti-carcinogenic, anti-viral, anti-hypercholesterolemia, anti-hypertensive, anti-bacterial, and hypoglycemic actions. The synthesis of new stable CA derivatives can enhance its metabolic stability and biological activity., Conclusion: The present study represented different synthetic methods and biological activities of CA derivatives. These compounds showed high antioxidant activity across a wide range of biological effects. Our goal was to help other researchers design and develop stable analogs of CA for the improvement of its metabolic stability and the promotion of its biological activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Purpose: Fusarium species are commonly resistant to many antifungal drugs. The limited therapeutic options available have led to a surge of research efforts aimed at discovering novel antifungal compounds in recent decades. This study aimed to assess the in vitro antifungal activity of plant-based biosynthesized selenium nanoparticles (Se NPs) and six comparators against a set of clinical Fusarium strains., Materials and Methods: In vitro antifungal activity of Se NPs synthesized using plant extracts of Allium paradoxum , Crocus caspius , Pistacia vera L. hull, Vicia faba L. hull and Heracleum persicum , as well as six common antifungal drugs, namely voriconazole, itraconazole, amphotericin B, posaconazole, natamycin, and caspofungin were evaluated against 94 clinical Fusarium strains using broth microdilution according to Clinical and Laboratory Standards Institute guideline., Results: The obtained results were intriguing since all five types of biosynthesized Se NPs demonstrated significantly higher antifungal activity, compared to antifungal drugs. It was found that Se NPs synthesized by V. faba L. hull extract (0.03 μg/ml) had the lowest geometric mean minimum inhibitory concentration value followed by Se NPs synthesized by P. vera  L. hull extract (0.25 μg/ml), A. paradoxum extract (0.39 μg/ml), C. caspius extract (0.55 μg/ml), and H. persicum extract (0.9 μg/ml)., Conclusion: Plant-based Se NPs demonstrated supreme antifungal activity and could be considered promising antifungal agents for Fusarium infections. However, tests, such as toxicity and in vivo tests are needed before the product can be used in clinical settings., Competing Interests: The authors report no conflicts of interest., (Copyright: © 2021, Published by Mazandaran University of Medical Sciences on behalf of Iranian Society of Medical Mycology and Invasive Fungi Research Center.)

Background: Current chemical treatments for toxoplasmosis have side effects, researchers are looking for herbal remedies with minimal side effects and the best effectiveness. This study aimed to evaluate the anti-toxoplasmic effects of silver nanoparticles based on Sambucus ebulus (Ag-NPs-S. ebulus) and Feijoa sellowiana (Ag-NPs-F. sellowiana) fruit extracts, in vitro and in vivo., Methods: Vero cells were treated with different concentrations (0.5, 1, 2, 5, 10, 20, 40 μg/mL) of extracts and pyrimethamine as a positive control. Vero cells were infected with T. gondii and treated with extracts. The infection index and intracellular proliferation of T. gondii were evaluated. The survival rate of infected mice with tachyzoites of T. gondii was examined after intraperitoneal injection of the extracts at a dose of 40 mg/kg/day for 5 days after infection., Results: The Ag-NPs-S. ebulus and Ag-NPs-F. sellowiana, almost similar to pyrimethamine, reduced proliferation index when compared to untreated group. Also, high toxoplasmicidal activity was observed with Ag-NPs-S. ebulus extract. Mice in the treatment groups of Ag-NPs-S. ebulus and pyrimethamine achieved better results in terms of survival than the others., Conclusion: The results indicated that Ag-NPs-F. sellowiana and S. ebulus have a significant growth effect on T. gondii in vitro and in vivo. Ag-NPs-S. ebulus extract has a more lethal effect on the parasite than Ag-NPs-F. sellowiana. It is suggested that in future investigate the induction of Toxoplasma-infected cell apoptosis using nanoparticles., (© 2023. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)

Introduction: Scientists are especially interested in polyphenols, particularly flavonoids. Quercetin, a flavonoid, has demonstrated various therapeutic properties, such as antioxidant, anti-diabetic, anti-hypertensive, and anti-carcinogenic activities. Different plant sources contain varying quantities and types of quercetin. However, quercetin's bioavailability is frequently low due to its low water solubility, molecular stability, and absorption characteristics., Areas Covered: The primary goals of this review are related to the approaches for overcoming quercetin's limitations. Hence, the main tactics for structural modifications (addition of charged and polar groups, removing C2, C3 double bond or reducing aromaticity, disrupting intramolecular H-bond, and reducing crystal lattice stability) and drug delivery systems (cyclodextrin complexes, emulsions, nanoparticles, liposomes, etc.) were discussed to improve water solubility and bioavailability of quercetin., Expert Opinion: From a tactical perspective, enhancing the solubility of compounds can be simplified through decreasing hydrophobic properties or crystalline stability. In addition, an essential field of study focuses on creating appropriate molecular carriers for substances with low water solubility. However, pharmacokinetics, potency, and toxicology are all impacted by the structural factors and physical characteristics that regulate solubility. Poor water solubility is still a major problem in drug discovery, and new methods are always in demand to overcome it.

Increasing antimicrobial resistance and the development of multi-drug resistant (MDR) Pseudomonas aeruginosa is dependent on the expression of efflux pumps. This study aimed to investigate the role of overexpression of MexCD-OprJ and MexEF-OprN efflux pumps in reduced susceptibility to antimicrobial agents among P. aeruginosa strains. Totally, 100 clinical isolates of P. aeruginosa were collected from patients and the strains were identified by standard diagnostic tests. The MDR isolates were detected using the disk agar diffusion method. The expression levels of MexCD-OprJ and MexEF-OprN efflux pumps were evaluated by the real-time PCR. Forty-one isolates showed MDR phenotype, while piperacillin-tazobactam and levofloxacin were the most- and least-effective antibiotics, respectively. Also, all 41 MDR isolates showed a more than tenfold increase in the expression of mexD and mexF genes. In this study, a significant relationship was observed between the rate of antibiotic resistance, the emergence of MDR strains, and increasing the expression levels of MexEF-OprN and MexCD-OprJ efflux pumps (P < 0.05). Efflux systems mediated resistance was a noteworthy mechanism causative to multidrug resistance in P. aeruginosa clinical isolates. The study results demonstrated mexE and mexF overexpression as the primary mechanism conferring in the emergence of MDR phenotypes among P. aeruginosa strains. In addition, we also show that piperacillin/tazobactam exhibited a stronger ability in the management of infections caused by MDR P. aeruginosa in this area., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Modern research revealed that plants belonging to the Sida rhombifolia family (Malvaceae) contain biologically active compounds that make them prone to discovering and developing anticancer drugs. This study aimed to evaluate the apoptosis effects of S. rhombifolia extracts in HepG2 Cell Line was performed., Methods: The extractions were prepared, and an MTT assay was applied to evaluate its role in decreasing the viability of HepG2 and HFF cells. Phenolic compounds were analyzed using High-performance liquid chromatography (HPLC). FlowCytometry and RT-qPCR evaluated apoptosis was performed to measure the mRNA expression of pro-and anti-apoptotic mediators., Results: The results can be summarized as EtOAc extract was more cytotoxic against the HepG2 cells (IC50= 364.3 µg/mL) compared to MeOH and HEX extracts (720.2 µg/mL) (560.4 µg/mL) with less cytotoxicity in HFF cells (353.2 µg/mL). The HPLC analysis results revealed most phenolic compounds, such as Epicatechin(1.3 mg/g). The EtOAc extract (300 μg/mL) induced 34% apoptosis in HepG2 cells. RT-qPCR data showed upregulation of the proapoptotic gene (Bax) and increased Bax/BCL-2 ratio by S. rhombifolia EtOAc extract (300 μg/mL)., Conclusion: In conclusion, the EtOAc extract of S. rhombifolia is capable of inducing apoptosis in HepG2 cells through modulation of the mitochondrial pathway, which explains their antitumor activity.

A novel quinazoline-based colorimetric sensor (probe 1) that detected Fe 3+ via naked-eye in a buffered MeOH: H 2 O (8:2) solvent system within a neutral pH range was synthesized and its structure was confirmed by 1 H-NMR, 13 C-NMR, FT-IR, and Mass spectroscopy. Its photophysical properties were also studied. The sensitivity and selectivity factor in the presence of 16 metal ions was examined by utilizing absorption titrations. Based on the selectivity test, probe 1 exhibited excellent selectivity and sensitivity toward Fe 3+ ions among various other ions. The competitive effect indicated relatively low interference of other cations on the interaction of probe 1/Fe 3+ . To specify the sensing behavior of probe 1 to Fe 3+ , the mole ratio method was carried out. After addition of around 500 µL of Fe 3+ , the absorption of probe1 reached saturation, and the reaction was completed. The effect of pH on the absorption and stability of probe 1 towards Fe 3+ was examined. The pH range from 5.0 to 9.0 was appropriate for detection of Fe 3+ . To find the binding stoichiometric of the complex, Job's plot studies were carried out by varying the molar ratio of Fe 3+ . A 1:2 binding ratio was proposed. Under the optimal conditions, a good linear relationship (R 2  = 0.9886) was at the concentration of Fe 3+ over the range of 50-110 µM, with a detection limit of 47.44 nM. Our quinazoline-based probe has shown good results for the quantitative determination of Fe 3+ in samples of urine with high recovery., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Diabetic wounds are one of the most important issues in diabetic patients. It seems that Juglans regia L. leaf with antioxidant and anti-inflammatory potentials can be profitable for healing of diabetic wounds. The aim of present study was to investigate the topical administration of Juglans regia L. leaf extract in diabetic wound healing., Methods: Seventy-five diabetic male rats were randomly divided into 5 groups (n = 15), including: untreated (Control) group, Eucerin group, 2% Juglans regia L. ointment (JRL 2%) group, 5% Juglans regia L. ointment (JRL 5%) group, and Phenytoin group as a reference drug. Sampling was performed at days 7, 14, and 21 after surgery. Evaluation tests included stereology, immunohistochemistry, molecular, and biomechanical., Results: Our results showed that the wound closure rate, volumes of newly formed of epidermis and dermis, density of fibroblasts and blood vessels, collagen deposition, density of proliferation cells, expression levels of TGF-β and VEGF genes, and biomechanical characteristics were significantly higher in extract groups compared to control and eucerin groups, however, these changes were considerable in the JRL 5% group (P < 0.05). This is while that the density of neutrophils and expression levels of TNF-α and IL-1β genes in the extract groups, especially in the JRL 5% group, were significantly reduced compared to control and eucerin groups (P < 0.05)., Conclusion: Topical administration of Juglans regia L. leaf extract, especially in 5% concentration, considerably accelerates diabetic wound healing., (© 2022. The Author(s).)

A wide variety of medical, biomedical, and industrial applications has been reported for quinoxalines derivatives. In this work, a novel quinoxaline derivative was designed and synthesized. Naked-eye and quantitative detection of Fe 3+ among several cations were evaluated using UV-Vis spectroscopy. New chemosensor, 2,3-bis(6-bromopyridine-2-yl)-6-chloroquinoxaline named BPQ, showed a selective interaction for iron ion over other tested cations by changing color. Iron overloaded mice were prepared as a thalassemia model and then the effects of iron-chelating activities of BPQ were experienced. The job's plot methods determined the stoichiometric ratio of ligand to Fe 3+ (1:1). The iron content in serum was evaluated by atomic absorption spectroscopy (AAS). Results showed significant differences (two-fold decrease in total iron and Fe 3+ ) between the iron overloaded and BPQ (dose of 20 mgkg-1). The BPQ was identified as a ligand, which can be applied as a new chelator for decreasing the excess iron of blood., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim of this study was to evaluate the anti-inflammatory and wound-healing potential of Feijoa sellowiana fruit extract using stereological and molecular methods in experimental rat models., Materials: Male Wistar rats were divided into four equal groups: non-treated, vehicle, Feijoa sellowiana fruit extract ointment (5% weight/weight) and the reference drug (madecassol). All animals were treated topically once per day. At the end of the study, wound samples were harvested for histological, stereological, immunohistochemical and molecular assessments to determine the in vivo healing potential and anti-inflammatory activity. A high-performance liquid chromatography (HPLC) analysis was performed for the characterisation of the phenolic acids in the extract., Results: The study included 64 rats in total. Our results showed that the wound closure, volume of new epidermis and dermis, density of fibroblasts and blood vessels, and the deposition of collagen were significantly higher in both extract and madecassol groups compared to the non-treated and vehicle groups, with superior healing in the extract group. The transcript for the transforming growth factor (TGF )-β gene was significantly upregulated in both extract and madecassol groups compared to non-treated and vehicle groups and was highest for the extract group. The density of inflammatory cells and expression levels of the cyclooxygenase (COX)-2 protein and tumour necrosis factor (TNF )-α gene in the extract and madecassol groups, especially in the extract group, were significantly reduced compared to non-treated and vehicle groups., Conclusion: Our results confirm that the Feijoa sellowiana fruit extract is a valuable source of antioxidant and anti-inflammatory activities and can allow for damaged tissue in wounds to recover markedly.

Having broad specificity for xenobiotics metabolism throughout the body, cytochrome P450 (CYP) isoform 1A1 is of key relevance for carcinogenesis. However, the oncogenic potential of its altered transcription and the underlying mechanism has not been well-established in breast cancer. Direct bisulfite sequencing PCR (BSP) of the CYP1A1 promoter, enriched by 113 CpGs within and flanking the xenobiotic response elements (XREs) 2 to 10, in paired cancerous and normal tissues from 40 breast cancer patients revealed three distinctly methylated patterns; unmethylated (XREs 2 to 6) and completely methylated (XREs 7 and 8) CpGs, in common for the normal and cancerous tissues, and a putative 171bp CpG block (XREs 9 and 10) contiguously hypermethylated in the tumor tissues. Increased transcription of CYP1A1, observed for the cancerous tissues, was correlated with the hypermethylation of given CpG block, besides simultaneously being associated with upregulation of the anti-apoptotic BCL-2. Clinical value of the methylation changes, investigated based on the comparisons between the tissue cohorts of different clinicopathological features, exhibited gradual hypermethylation of the corresponding CpG block following disease progression as well as lymphatic involvement. Hypermethylation of given CpG block may has potential to be used as a biomarker for diagnosis and progression of breast cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Quinoxaline derivatives are well-known N-heterocycles with pharmacological and fluorescence activities. Almost all quinoxaline derivatives with extensive π-conjugation have been introduced as fluorophores which emit blue and green light. For the first time, we designed and synthesized 6-chloro-2,3 di(Pyridine-2yl) quinoxaline (2-CPQ) as a pink fluorophore in acetonitrile medium by simple route at room temperature whitin 30 min. The synthesized quinoxaline was identified using 1 H, 13 C NMR, MS, and FT-IR spectroscopy. Our results showed that the iodine-catalyzed method for both oxidation and cyclization during the synthesis of quinoxaline from pyridine 2-carbaldehyde was straightforward, efficient, and clean. All of the mentioned characterization devices confirmed the synthesis of 2-CPQ.Moreover, we studied the photophysical properties of the synthesized fluorophore in which The UV-Vis absorption spectrum of 2-CPQ in DMF were three peaks at 451, 518 and 556 nm. Based on photophysical properties investigation, 2-CPQ shows good fluorescence with maximum peaks 607 and 653 nm in DMF as solvent (ф F  = 0.21). Hence, the fluorophore was applied in the peroxyoxalate chemiluminescence system. The reaction of imidazole, H 2 O 2, and bis (2,4,6-trichlorophenyl) oxalate (TCPO) can transfer energy to a 6-chloro-2,3 di(pyridine-2yl) quinoxaline. In this process, dioxetane was synthesized, which chemically initiated the electron exchange luminescence (CIEEL) mechanism and led to pink light emission. We anticipate our synthesized fluorophores 2-CPQ will have great potential applications in imaging and medical markers., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

More studies are needed to develop new drugs for problems associated with drug resistance and unfavorable side effects. The natural flavonoid of quercetin revealed a wide range of biological activities by the modulation of various targets and signaling pathways. However, quercetin's low solubility and poor bioavailability have restricted its applicability; as a result, researchers have attempted to design and synthesize numerous novel quercetin derivatives using various methodologies in order to modify quercetin's constraints; the physico-chemical properties of quercetin's molecular scaffold make it appealing for drug development; low molecular mass and chemical groups are two of these characteristics. Therefore, the biological activities of quercetin derivatives, as well as the relationship between activity and chemical structure and their mechanism of action, were investigated. These quercetin-based molecules could be valuable in the creation and discovery of medications for a number of diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Quercetin as a valuable natural flavonoid has shown extensive biological activities, including anticancer, antioxidant, antibacterial, antiinflammatory, anti-Alzheimer, antifungal, antiviral, antithalassemia, iron chelation, antiobesity, antidiabetic, antihypertension, and antiphospholipase A2 (PLA2) activities, by the modulation of various targets and signaling pathways that have attracted much attention. However, the low solubility and poor bioavailability of quercetin have limited its applications; therefore, the researchers have tried to design and synthesize many new derivatives of quercetin through different strategies to modify quercetin restrictions and improve its biological activities. This review categorized the O-glycoside derivatives of Quercetin into two main classes, 3-O-glycoside and other O-glycoside derivatives. Also, it studied biological activities, structure-activity relationship (SAR), and the action mechanism of O-glycoside quercetin derivatives. Overall, we summarized past and present research for discovering new potent lead compounds. HIGHLIGHTS: Quercetin is a natural flavonoid with a valuable scaffold. O-Glycoside quercetin derivatives represents broad-spectrum biological activities. The structure-activity relationship investigation is discussed after modifying the scaffold of quercetin. This review can help researchers to rationally design/develop various drugs., (© 2021 John Wiley & Sons, Ltd.)

Background: Little is known about cytochrome P450 3A4 (CYP3A4) DNA methylation and transcription alterations in gastric cancer., Objective: In this paper, we initially aimed to address the effect of diazinon pesticide on DNA methylation and transcription changes of the CYP3A4 gene in a human gastric cell line. In the next step, we studied the methylation differences of CpG sites within the upstream regulatory regions of the CYP3A4 gene among human gastric cancerous and healthy tissues., Methods: For the in vitro assay, the methylation changes of the C/EBP response element and transcript level of the CYP3A4 gene were studied following treatment of the AGS cell line with various concentrations of diazinon pesticide. In the next phase, the methylation percentages of 24 CpG sites within or around the upstream regulatory elements, including near promoter, C/EBP binding site, XREM, and CLEM4, in 11 specimens of human gastric cancer tissue were compared to their adjacent healthy tissues., Results: Treatment with 10 μM Diazinon significantly increased the CYP3A4 gene transcription by approximately 27-fold, which was correlated with the hypermethylation of 3 CpGs in C/EBP binding sites, including -5998, -5731 and -5725 (p<0.001 for all comparisons). Results of bisulfite sequencing revealed that the CpG sites which are located in -1521 (p=0.003), -1569 (p=0.027), -10813 (p=0.003), -10851 (p=0.001) and -10895 (p=0.0) bp from transcription start site, were significantly hypermethylated in cancerous tissues comparing to their healthy cohort., Conclusion: Hypermethylation of CLEM4 and a region near the core promoter may have a significant association with gastric cancer incidence., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Inherited beta-thalassemia is caused by irregular production of hemoglobin through reducing beta-globin chains. It has been observed that increasing fetal hemoglobin (HbF) production improves symptoms in the patients; thus, it has been an operative approach to treat patients with betathalassemia. This review represents compounds with biological activities and pharmacological properties that can be useful in promoting the HBF level in β-thalassemia patients. Various natural products with different mechanisms of action can be helpful in this medication cure. Clinical trials were efficient in improving the signs of patients. Association of in vivo, and in vitro studies of HbF induction and γ-globin mRNA growth displays that in vitro experiments could be an indicator of the in vivo response. The current study resulted that; (a) HbF inducers can be grouped into several classes based on their chemical structures and mechanism of actions; (b) According to several clinical trials, wellknown drugs such as hydroxyurea and decitabine are useful HbF inducers. (c) The cellular biosensor K562 carrying genes under the control of the human γ-globin and β-globin gene promoters were applied during the researches. (d) New natural products and lead compounds were found based on various studies as HbF inducers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Ferula persica is one of the most important traditional medicinal plants that is used to treat various diseases such as diabetes, backache and rheumatism. The aim of the present study was to evaluate the anti-inflammatory and wound healing potential of F. persica using stereological and molecular methods in experimental models., Methods: In the present study, two wound models (circular excision and linear incision) were used. Male Wistar rats were divided into four groups (n = 16), including control, vehicle treated, treated with F. persica extract ointment (5% w/w) and treated with the reference drug (Madecassol). All the animals were treated topically once a day. The circular and linear wounds were treated for 9 and 17 days, respectively. At the end of the study, samples from wounds area were harvested for histology, stereology, immunohistochemistry and molecular assessments to determine the in vivo healing potential and anti-inflammatory activity., Results: We observed significant recovery in macroscopic evaluation of wound healing in the F. persica extract treated group compared with the control and vehicle treated groups (p < 0.05). Histological and stereological assessments showed complete repair of the epidermal layer, increasing fibroblast cells and collagen density, decreasing inflammatory cells and a remarkable degree of neovascularization by determining length density of blood vessels in the extract group, which were significant as compared to the control and vehicle treated groups (p < 0.05). Expressions of TNF-α and TGF-β were found to be decreased and increased (p > 0.05, p < 0.05, respectively), in the extract treated group as compared to the control and vehicle treated groups. Also, greater COX-2 expression could be detected in the control and vehicle treated groups, which was significantly attenuated in the extract group., Conclusion: Our results confirm that the F. persica extract is a valuable source of antioxidant and anti-inflammatory activity and can allow damaged tissue in wounds to recover markedly., (© 2021 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Breast cancer [BC] is one of the most common cancers among women, one of the leading causes of a considerable number of cancer-related death globally. Among all procedures leading to the formation of breast tumors, angiogenesis has an important role in cancer progression and outcomes. Therefore, various anti-angiogenic strategies have been developed so far to enhance treatment's efficacy in different types of BC. Vascular endothelial growth factors [VEGFs] and their receptors are regarded as the most well-known regulators of neovascularization. VEGF binding to vascular endothelial growth factor receptors [VEGFRs] provides cell proliferation and vascular tissue formation by the subsequent tyrosine kinase pathway. VEGF/VEGFR axis displays an attractive target for anti-angiogenesis and anti-cancer drug design. This review aims to describe the existing literature regarding VEGFR inhibitors, focusing on BC treatment reported in the last two decades., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Heterocyclic compounds create an important class of molecules that demonstrates various chemical spaces for the definition of effective medicines. Many N-heterocycles display numerous biological activities. Among condensed heterocycles, pyrazolotriazine derivatives have received the attention of researchers owing to the extensive spectrum of biological activities. The reactivity of identified compounds was similar to the free azoles and triazines. The pyrazolotriazine scaffold exhibited antiasthma, antiinflammatory, anticancer, antithrombogenic activity and showed activity for major depression and pathological anxiety. Pyrazolotriazine derivatives also exhibited antibacterial, anticancer, antimetabolites, antidiabetic, antiamoebic, anticonvulsant, antiproliferative activity, human carbonic anhydrase inhibition, cyclin-dependent kinase 2 inhibition, tyrosinase and urease inhibition, MAO-B inhibition, TTK inhibition, thymidine phosphorylase inhibition, tubulin polymerization inhibition, protoporphyrinogen oxidase inhibition, GABA A agonistic activity, hCRF1 receptor antagonistic activity, and CGRP receptor antagonistic activity. This paper structurally categorized various pyrazolotriazines to isomeric classes into six groups that containing pyrazolo [1,5-d] [1,2,4] triazine, pyrazolo [5,1-c] [1,2,4] triazine, pyrazolo [3,4-e] [1,2,4] triazine, pyrazolo [4,3-e] [1,2,4] triazines, pyrazolo [1,5-a] [1,3,5] triazine, and pyrazolo [3,4-d] [1,2,3] triazine and expressed biological activity, the synthetic procedures for each class of pyrazolotriazines, structure-activity relationship and their mechanism of action. Generally, this review summarily indicated the past and present studies about the discovery of new lead compounds with good biological activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Multifunctional nature of phytochemicals and their chemical diversity has attracted attention to develop leads originated from nature to fight COVID-19. Pharmacological activities of chelerythrine and its congeners have been studied and reported in the literature. This compound simultaneously has two key therapeutic effects for the treatment of COVID-19, antiviral and anti-inflammatory activities. Chelerythrine can prevent hyper-inflammatory immune response through regulating critical signaling pathways involved in SARS-CoV-2 infection, such as alteration in Nrf2, NF-κB, and p38 MAPK activities. In addition, chelerythrine has a strong protein kinase C-α/-β inhibitory activity suitable for cerebral vasospasm prevention and eryptosis reduction, as well as beneficial effects in suppressing pulmonary inflammation and fibrosis. In terms of antiviral activity, chelerythrine can fight with SARS-CoV-2 through various mechanisms, such as direct-acting mechanism, viral RNA-intercalation, and regulation of host-based antiviral targets. Although chelerythrine is toxic in vitro, the in vivo toxicity is significantly reduced due to its structural conversion to alkanolamine. Its multifunctional action makes chelerythrine a prominent compound for the treatment of COVID-19. Considering precautions related to the toxicity at higher doses, it is expected that this compound is useful in combination with proper antivirals to reduce the severity of COVID-19 symptoms.

Almost all plants contain polyphenols. Literature shows that polyphenols exhibit many biological activities. Little has known about their protective effects against hypoxia-induced lethality. The protective effects of rutin (1) and chlorogenic acid (2) against hypoxia conditions in mice were determined by three different experimental models. Antihypoxic activity was especially pronounced in asphytic hypoxia. Both compounds (1&2) showed statistically significant (p>0.05) activities respect to the control. Compound (1) significantly prolonged the latency for death with respect to control (39.20±8.70 vs. 13.20±2.58min, p<0.001). Compound (1) was the most effective compound in circulatory hypoxia. It significantly prolonged the latency for death with respect to control (14.44±2.82 vs. 9.82±0.79 min, p<0.01). On the other hand, Chlorogenic acid (2) at a dose of 100 mg kg -1 kept mice alive for 12.76±1.30min (p>0.05). None of two phenolic acids had any activity in haemic hypoxia when compared to control.

Objective: Sambucus ebulus (SE), a famous traditional Iranian medicine, is grown in the north of Iran. As a traditional medicine with anti-inflammatory effects, SE has been utilized against inflammatory joint diseases, insect bites, infectious wounds, edema, and eczema. Type1 diabetes, is an autoimmune disease, characterized by the destruction of pancreatic beta cells by the immune system. For the first time, we investigated the effect of methanolic extract of SE on CD4+, CD8+ and regulatory T cells in experimental type 1 diabetes (T1D)., Materials and Methods: In this experimental study, fifty-six C57BL\6 mice in 8 groups (G1-G8), were enrolled. Diabetes was induced by a multiple low-dose streptozotocin (MLDS) protocol and mice were daily treated with SE extract at 200 and 400 mg/kg doses, for 35 days. Fasting blood glucose was weekly measured by a glucometer. Islets insulin content was analyzed by immunohistochemistry. Percentage of CD4+, CD8+ and regulatory T cells and cytokines production levels were evaluated by flow cytometer and ELISA, respectively., Results: The clinical symptoms of diabetes were significantly alleviated in G2 group mice which received 400 mg/ kg SE extract. Immunohistochemistry analysis showed that the insulin content of islets increased in G2 group mice. Immunophenotyping analysis indicated that the percentage of CD4+ and CD8+ T cells in G2 group mice was significantly decreased. SE extract significantly increased the percentage of regulatory T cells. The extract in G2 and G4 groups mice significantly decreased IFN-γ and IL-17levels. The extract significantly increased IL-10 in G2 group mice., Conclusion: The protective effect of SE extract in MLDS-induced diabetes could be partly due to a decrease of CD4+ and CD8+ T cells and an increase of Treg cells resulting in an inflammation reduction in the pancreatic islets., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Adaptation to the loss of O2 is regulated via the activity of hypoxia-inducible factors such as Hypoxia-Inducible Factor-1 (HIF-1). HIF-1 acts as a main transcriptional mediator in the tissue hypoxia response that regulates over 1000 genes related to low oxygen tension. The role of HIF-1α in oncogenic processes includes angiogenesis, tumor metabolism, cell proliferation, and metastasis, which has been examined in various malignancies, such as melanoma. Melanoma is accompanied by a high death rate and a cancer type whose incidence has risen over the last decades. The linkage between O2 loss and melanogenesis had extensively studied over decades. Recent studies revealed that HIF-1α contributes to melanoma progression via different signaling pathways such as PI3K/Akt/mTOR, RAS/RAF/MEK/ERK, JAK/STAT, Wnt/β-catenin, Notch, and NF-κB. Also, various microRNAs (miRs) are known to mediate the HIF-1α role in melanoma. Therefore, HIF-1α offers a diagnostic/prognostic biomarker and a candidate for targeted therapy in melanoma., (Copyright © 2021. Published by Elsevier Masson SAS.)

Osteoarthritis is the most common cause of disability and aging is the major risk factor. One of the low-risk herbal medicines for reducing pain and inflammation in persian medicine is Pistacia atlantica gum. A triple-blind placebo-controlled clinical trial was performed in order to evaluate the efficacy of P. atlantica gum ointment on knee osteoarthritis in elderly people. A total of 60 patients were randomly allocated to two groups. The intervention group used 4% P. atlantica ointment and the control group used placebo, topically applied three times a day, for 8 weeks. The patients were evaluated before and after the intervention using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale. There were significant differences (p < .001) between two the groups in terms of joint stiffness and pain as well as function. Within groups, regarding the effect size (EF) in joint stiffness was 2.82 and 0.74 in the Pistacia and placebo groups, respectively. Regarding pain, the effect size of the intervention and placebo groups were 3.90 and 0.99, respectively. In addition, regarding function, the effect size of the intervention and the placebo groups were 4.33 and 1.17, respectively. Therefore, it seems that topical P. atlantica is significantly better than the placebo in the old patients with knee osteoarthritis., (© 2021 John Wiley & Sons Ltd.)

Many pharmacological activities have been reported from plants polyphenols. The aim of this study was to investigate anti inflammatory and antinociceptive activities of polyphenols from Feijoa sellowiana fruit and leaves. For the anti-inflammatory activity evaluation, inhibition of carrageenan induced edema was used. While for the evaluation of antinociceptive activity of the extract, writhing and hot plate tests in mice were used. Impairment in mouse coordination was evaluated by rota-rode test. Carrageenan induced edema was significantly inhibited by the extract at 50-400 mg kg -1 doses, when comparison was made with control group. The extract of leaf at the dose of 50 mg kg -1 i.p. the activity was equipotent with diclofenac (p>0.05). Extract reduced the writhing count in 50-400 mg kg -1 of doses. Fruit extract showed higher activity than diclofenac (p<0.001) at 400 mg kg -1 doses. In all tested doses, the extract significantly augmented the pain threshold in hot plate thermal test. No locomotor impairment in mice was induced by the extract at any tested doses. Extract was safe and didnot demonstrate any noxiousness up to 1 g kg -1 .This study indicates the potential therapeutic use of Feijoa as a potent anti-inflammatory and antinociceptive agent.

Background: The preliminary report of the RECOVERY large randomised controlled trial indicated a promising survival effect for dexamethasone therapy of coronavirus disease 2019 (COVID-19). This study aimed to investigate the anti-hypoxic activities of dexamethasone to understand a possible mechanism of its action in hypoxia-induced lethality through experimental models of hypoxia., Methods: In this investigation, 84 Male BALB/c mice were randomly divided into groups of seven (12 groups). Treatment groups received 10 days of dexamethasone intraperitoneal injection at both human dose (~0.1 mg/kg) and the animal does (~1 mg/kg). Control negative and positive groups were treated with 10 ml/kg of normal saline and 30 mg/kg of propranolol, respectively. Three experimental models of hypoxia, asphyctic, circulatory, and hemic were applied in this study., Results: The findings showed that dexamethasone significantly prolonged the latency for death in the asphyctic model concerning the control group in both humans (P < .0001) and animal dose (P < .0001). The results were also highly significant for both doses in the hemic model (P < .001). In the circulatory model, although a small increase was observed in death prolongation, results were not statistically significant for both doses in this model (P > .05)., Conclusions: This experimental in vivo investigation demonstrated an excellent protective effect for 10 days of dexamethasone treatment against hypoxia, especially in asphyctic and hemic models. In addition to promising dexamethasone outcomes, using propranolol as the positive control illustrated a very substantial anti-hypoxic effect even much better than dexamethasone in all models. It seems that propranolol would be a safe, potential, and prudent choice to invest in treating COVID-19 patients., (© 2020 John Wiley & Sons Ltd.)

The purpose of the present study was to investigate the protective potential of Feijoa fruit extract on cadmium chloride (CdCl 2 )-induced testicular injury and pituitary-gonadal axis. Adult male Wistar rats were randomly divided into four groups: (a) control (normal saline, orally), (b) cadmium chloride (0.1 mg/kg, single dose, intraperitoneally), (c) Feijoa fruit extract (400 mg/kg, orally for 30 consecutive days) and (d) CdCl 2  + Feijoa fruit extract. One day after receiving the last medicine, the LH, FSH, prolactin and testosterone concentration were assayed. Also, sperm parameters and tissue structure of the testis were evaluated. Administration of Feijoa fruit extract after CdCl 2 injection in rats ameliorated sperm parameters such as sperm count, morphology, motility and sperm viability, increased levels of LH, FSH, prolactin and testosterone and improved testicular histology. According to the results of this study, it was shown that Feijoa can reduce the destructive side effects of CdCl 2 on testicular tissue and sex hormones of the pituitary-gonadal pathway., (© 2020 Wiley-VCH GmbH.)

Background: Cancer is defined as an abnormal/uncontrolled cell growth that shows rapid cell division. This disease is annually recognized in more than ten million people. Nanomaterials can be used as new strategies for cancer therapy. Nanostructured devices have been developed for drug delivery and controlled release and created novel anticancer chemotherapies. Nanomaterials were taken into consideration because of their new properties, containing a large specific surface area and high reactivity. Copper Oxide Nanoparticles (CuONPs) have potential applications in many fields like heterogeneous catalysis, antibacterial, anticancer, antioxidant, antifungal, antiviral, imaging agents, and drug delivery agents in biomedicine. CuONPs display different physical properties, such as high-temperature superconductivity, electron correlation effects, and spin dynamics. NPs can be synthesized using different methods like physical, chemical, and biological methods., Methods: Copper Oxide Nanoparticles (CuONPs) have been suggested for its broad usage in biomedical applications. In this review, we tried to exhibit the results of significant anticancer activity of green synthesized CuONPs and their characterization by different analytical techniques such as UV-Vis, FT-IR, XRD, EDAX, DLS, SEM, and TEM., Results: The green method for the synthesis of CuO nanoparticles as eco-friendly, cost-effective, and facile method is the more effective method. Synthesized CuONPs from this method have an appropriate size and shape. The Green synthesized CuONPs exhibited high potential against several breast cancer (AMJ-13, MCF-7, and HBL-100 cell lines), cervical cancer (HeLa), colon cancer (HCT-116), gastric cancer (human adenocarcinoma AGS cell line), lung cancer (A549), leukemia cancer, and other cancers with the main toxicity approach of increasing ROS production., Conclusion: The present review confirms the importance of green synthesized CuO nanoparticles in medical science especially cancer therapy that exhibited high activity against different cancer, both in vitro and in vivo. The main toxicity approach of CuONPs is increasing the production of Reactive Oxygen Species (ROS). It needs to perform more studies about in vivo cancer therapy and following clinical trial testing in the future. We believe that green synthesized CuO nanoparticles can be used for the improvement of different diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Heterocyclic compounds play a critical role in medicinal chemistry, and many available drugs contain heterocyclic rings. A six-membered heterocyclic compound, pyridine, showed various applications, including being an important solvent, reagent, and precursor in agrochemicals and pharmaceuticals. Due to the increase in drug resistance, there is an apparent medical need to develop new antiviral agents. Various derivatives of pyridine scaffold display broad biological activities such as anti-microbial, antiviral, antioxidant, anti-diabetic, anti-cancer, anti-malarial, analgesic, and antiinflammatory activities. Furthermore, they display psychopharmacological, antagonistic, anti-amoebic agents, and anti-thrombic activities. Due to the high importance of pyridine derivatives, in the present review, we tried to collect and classify many pyridine derivatives based on their structures from 2000 to 2020. Pyridine derivatives were classified into two general categories, including pyridine containing heterocycles and pyridine fused rings. The structure-activity relationship (SAR) and the action mechanism of derivatives were also investigated. According to the recent studies, these derivatives exhibited good antiviral activity against different types of viruses such as the human immunodeficiency viruses (HIV), the hepatitis C virus (HCV), the hepatitis B virus (HBV), respiratory syncytial virus (RSV), and cytomegalovirus (CMV). These derivatives inhibited viral application with different action mechanism such as RT inhibition, polymerase inhibition, inhibition of RNase H activity, inhibition of maturation, inhibition of the viral thymidine kinase, AAK1 (Adaptor-Associated Kinase 1) inhibition, GAK (Cyclin G-associated kinase) inhibition, inhibition of post-integrational event, inhibition of HDAC6, CCR5 antagonistic activity, DNA and RNA replication inhibition, gene expression inhibition, cellular NF-jB signaling pathway and neuraminidase (NA) inhibition, protein synthesis inhibition, and generally inhibition of viral replication cycle. This paper summarized the past and present results about the discovery of novel lead compounds with good antiviral activity. Studies exhibited that almost all of the evaluations were performed by way of in vitro testing. It is necessary to investigate in vivo and clinical testing for better evaluations in the future. We believe that pyridine derivatives can be used as promising antiviral agents and more broad investigations in this field need to be performed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Mg 2+ is an important cation in our body. It is an essential cofactor for many enzymes. Despite many works, nothing is known about the protective effects of MgSO 4 against hypoxia-induced lethality and oxidative damage in brain mitochondria. In this study, antihypoxic and antioxidative activities of MgSO 4 were evaluated by three experimental models of induced hypoxia (asphyctic, haemic, and circulatory) in mice. Mitochondria protective effects of MgSO 4 were evaluated in mouse brain after induction of different models of hypoxia. Antihypoxic activity was especially pronounced in asphyctic hypoxia, where MgSO 4 at dose 600 mg/kg showed the same activity as phenytoin, which used as a positive control ( P < 0.001). In the haemic model, MgSO 4 at all used doses significantly prolonged latency of death. In circulatory hypoxia, MgSO 4 (600 mg/kg) doubles the survival time. MgSO 4 significantly decreased lipid peroxidation and protein carbonyl and improved mitochondrial function and glutathione content in brain mitochondria compared to the control groups. The results obtained in this study showed that MgSO 4 administration has protective effects against lethality induced by different models of hypoxia and improves brain mitochondria oxidative damage., Competing Interests: The authors declared no conflicts of interest., (Copyright © 2020 Hamidreza Mohammadi et al.)

Objective: A systematic review and meta-analysis was carried out to examine the role of hydroxychloroquine (HCQ) in the treatment of COVID-19., Methods: We performed a systematic search in PubMed, Scopus, Embase, CochraneLibrary, Web of Science, Google Scholar, and medRxiv pre-print databases using available MeSH terms for COVID-19 and hydroxychloroquine. Data from all studies that focused on the effectiveness of HCQ with or without the addition of azithromycin (AZM) in confirmed COVID-19 patients, which were published up to 12 September 2020, were collated for analysis using CMA v.2.2.064., Results: Our systematic review retrieved 41 studies. Among these, 37 studies including 45,913 participants fulfilled the criteria for subsequent meta-analysis. The data showed no significant difference in treatment efficacy between the HCQ and control groups (RR: 1.02, 95% CI, 0.81-1.27). Combination of HCQ with AZM also did not lead to improved treatment outcomes (RR: 1.26, 95% CI, 0.91-1.74). Furthermore, the mortality difference was not significant, neither in HCQ treatment group (RR: 0.86, 95% CI, 0.71-1.03) nor in HCQ plus AZM treatment group (RR: 1.28, 95% CI, 0.76-2.14) in comparison to controls. Meta-regression analysis showed that age was the factor that significantly affected mortality ( P <0.00001)., Conclusion: The meta-analysis found that there was no clinical benefit of using either HCQ by itself or in combination with AZM for the treatment of COVID-19 patients. Hence, it may be prudent for clinicians and researchers to focus on other therapeutic options that may show greater promise in this disease.

Biogenic synthesis of silver nanoparticles (SNPs) has great attention of scientists, as it provides clean, biocompatible, non-toxic and inexpensive fabrication. In this study, F. sellowiana leaf extract was used for synthesizing SNPs which reduces silver nitrate into silver zero-valent. SNPs were characterized by UV, FTIR, XRD, SEM-EDS, and TEM analysis. They were also examined for their biological activities. The presence of biosynthesized SNPs was characterized by UV-visible spectroscopy and also crystal nature of SNPs was identified with XRD analysis. FT-IR spectrum was used to confirm the presence of different functional groups in the biomolecules which act as a capping agent for the nanoparticles. The morphology of SNPs was explored using SEM and the presence of silver was confirmed by elemental analysis. The size of the nanoparticles was in the range of 20-50 nm determined by TEM. The green synthesized SNPs showed good antibacterial activities against both gram-negative and gram-positive bacteria and also in resistant clinically isolated pathogens. Furthermore, the green synthesized SNPs showed reliable anticancer activity on the gastric adenocarcinoma (AGS) and breast (MCF-7) cancer cell lines with little effect on normal (HFF) cells. The  in-vitro  antioxidant activity of SNPs showed a significant effect on the scavenging of free radicals and iron chelating activity.

Resveratrol is a natural polyphenolic stilbene isolated from various plants, foods and beverages with a broad spectrum of biological and pharmacological properties through modulating diverse targets and signaling pathways. Particularly, it has attracted a great deal of attention as a promising and multitarget anticancer agent due to its potential use in chemoprevention and chemotherapy of various tumors. However, unfavorable pharmacokinetics/pharmacodynamics profile such as poor bioavailability restricted its applications. Therefore, medicinal chemists have synthesized a lot of novel derivatives and analogues of resveratrol using different modification strategies to overcome these limitations and improve anticancer efficacy. Herein, we reviewed the design, synthesis, structure-activity relationship and mechanism of the most potent and privileged resveratrol-based compounds that showed promising anticancer activities in the last five years. We classified these compounds into the ten different categories based on their chemical structure similarities., Competing Interests: Declaration of competing interest There is no actual or potential conflict of interest and our funding source has no role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Scientists are interested in biosynthesis of gold nanoparticles owing to their catalytic and biological features. In this research, the extract of Convolvulus fruticosus (C. fruticosus; CFE) extract was applied to synthesize spherical-like gold nanoparticles (CFE@AuNPs). As-prepared CFE@AuNPs was characterized by TEM, FE-SEM, XRD, FT-IR, EDS, UV-Vis and DLS analysis. Identification analysis revealed that the properties of as-prepared CFE@AuNPs with spherical morphology were homogeneous, regular, high dispersibility and low agglomeration. The particle size of biogenic gold nanoparticles (about 35 nm) was obtained using FE-SEM, TEM and DLS techniques. Photocatalytic experiment of CFE@AuNPs determined by degradation of basic violet 10 (BV10), basic blue 9 (BB9) and acid red 51 (AR51) pollutants with percent degradation of 94.3%, 90.2%, 85.4% under UV and 80.6%, 79.8%, 73.3% under visible light irradiation, respectively. As well as, as-prepared CFE@AuNPs illustrated as a significant inhibitory influence against ATCC strain for both gram-positive and gram-negative bacteria. Owing to the antibacterial results, CFE@AuNPs enhanced antibacterial activity against E. coli, A. baumannii, P. aeruginosa, S. aureus, K. pneumonia, P. mirabilis and E. faecalis with MIC of 0.075, 0.075, 0.075, 0.075, 0.15, 0.075 and 0.037 mg/ml, respectively. All in all, results of the findings showed that C. fruticosus capped gold nanoparticles can find applications in the various arena including biological and removal of toxic pollutants for water purification., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: Green nanotechnology is an interesting method for the synthesis of functional nanoparticles. Because of their wide application, they have set up great attention in recent years., Objective: The present research examines the green synthesis of Ag and zero-valent iron nanoparticles (AgNPs, ZVINPs) by Feijoa sellowiana fruit extract. In this synthesis, no stabilizers or surfactants were applied., Methods: Eco-friendly synthesis of Iron and biogenic synthesis of Ag nanoparticles were accomplished by controlling critical parameters such as concentration, incubation period and temperature. Scanning Electron Microscopy (SEM), Transmission Electron Microscope (TEM), Energy-Dispersive X-ray Spectroscopy (EDS), Fourier-Transform Infrared (FT-IR) spectroscopy, X-ray Diffraction analysis (XRD), Dynamic Light Scattering (DLS) and UV-Vis were applied to characterize NPs. The cytotoxicity of NPs was investigated in two cell lines, MCF-7 (breast cancer) and AGS (human gastric carcinoma). A high-performance liquid chromatography (HPLC) analysis was also performed for characterization of phenolic acids in the extract., Results: Both NPs displayed powerful anticancer activities against two tumor cell lines with little effect on BEAS-2B normal cells. Synthesized AgNPs and ZVINPs inhibited the growth of all selected bacteria. Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumonia, Staphylococcus aureus, Enterococcus faecalis, Acinetobacter baumannii and Escherichia coli have been studied in two stages. We initially examined the ATCCs followed by clinical strain isolation. Based on the results from resistant strains, we showed that nanoparticles were superior to conventional antibiotics. DPPH (diphenyl-1-picrylhydrazyl) free radical scavenging assay and iron chelating activity were used for the determination of antioxidant properties. Results showed a high antioxidant activity of scavenging free radicals for ZVINPs and powerful iron-chelating activity for AgNPs. Based on the HPLC data, catechin was the major phenolic compound in the extract., Conclusion: Our synthesized nanoparticles displayed potent cytotoxic, antibacterial and antioxidant activities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Nowadays the use of plant-derived products has been extensively examined in the treatment of many types of gastrointestinal cancers such as hepatocarcinoma and colon cancer. Urtica dioica is a traditional herb that has many pharmacological effects and wildly used as a therapeutic agent in cancer. Herein, we have evaluated the effects of the different concentrations of Methanolic Extract of Urtica dioica (MEUD) on viability, death pattern, and expression of the apoptosis-related gene in normal Human Dermal Fibroblast (HDF), hepatocarcinoma cell lines (HepG2) and colon-cancer cell line (HCT116)., Methods: A high-performance liquid chromatography method was developed to simultaneously separate 3 phenolic acids in MEUD. HepG2 and HCT116 cell lines as well as HDF normal cell line were cultured in suitable media. After 24 and 48h, in the cultured cell with different concentrations of MEUD, cells viability was assessed by MTT assay, and apoptosis was also evaluated at the cellular level by Annexin V/PI flow cytometry analyzing and AO/EB staining. BCL2 and BAX gene expressions were assessed by TaqMan real-time PCR assay., Results: MEUD showed antiproliferative effects on HepG2 and HTC116 cells after 48h with an IC50 value of about 410 and 420μg/ml, respectively (P < 0.001). Apoptotic cells were observed in HepG2 and HTC116 cells but not in HDF. Furthermore, the increased level of BAX/BCL-2 ratio was observed in HepG2 and HTC116 cells under the treatment of different concentrations of MEUD., Conclusion: The MEUD may influence hepatocarcinoma and colon-cancer cell lines at specific doses and change their proliferation rate by changing the expression of BAX and BCL2., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this work, a cost-effective/green/high-efficient/facile process for the preparation of silver nanoparticles using C. pentagyna (CP-AgNPs) fruit extractas as reducing agent and capping agent was reported. The influence of different parameters including temperature, pH, concentration and time were studied to reach optimum conditions. The as-synthesized CP-AgNPs were characterized using UV/Vis, XRD, SEM, TEM, EDS and DLS analysis. Regular, spherical morphology and homogeneous of CP-AgNPs with a mean particles size of 25-45 nm was determined from TEM images. The CP-AgNPs in presence of sunlight catalyzed the degradation of the organic contaminant dyes, rhodmine b (RhB), eosin (EY) and methylene blue (MB) with percent degradation of 85% and 70% and 78%, respectively. In addition, CP-AgNPs exhibit antibacterial activities against seven ATCC strains of bacteria and eight strains of drug-resistant bacteria. Due to the results, CP-AgNPs enhanced antimicrobial potential against S. aureus, E. faecalis, P. aeruginosa, A. baumannii and E. coli with MIC and MBC of (0.11, 7.1 µg/ml), (0.11, 1.7 µg/ml), (0.11, 0.22 µg/ml), (0.11, 0.22) and (0.11, 0.44 µg/ml), respectively. Generally, CP-AgNPs have excellent potential application for the photocatalytic degradation of organic pollutant and in the development of antibacterial materials., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: .Colorectal cancer (CRC) is now one the fourth cause of mortality and morbidity due to cancer throughout the globe. Cachexia is more prevalent in patients with this cancer and has a negative effect on response to chemotherapy and radiotherapy. Inflammatory cytokines such as TNF-α, IL-1β, and IL-6 could play a key role in cachexia. Moreover strong chemotherapy medications such as doxorubicin have complications such as toxicity and cachexia. Citrus unshiu Peel have been used as traditional herbal drugs for the treatment of cancer in traditional oriental medicine (TOM). Since its main components have anti-inflammatory effects, we evaluated the anti-cachexia activity in order to support the traditional usage of Citrus unshiu peel. Aim of the study; We aimed to assess the preventive or therapeutic effect of Citrus unshiu Peel Extract (CUPE) on cachexia by reducing of inflammatory cytokines in mice bearing C26 tumor. Also the contribution role of CUPE has evaluated on improvement of chemotherapy through reducing of inflammatory cytokines. Materials and Methods; The CUPE was prepared by Soxhlet extractor and quantitative and qualitative analysis of aqua extract was performed by high performance liquid chromatography (HPLC). C26 tumor bearing BALB/c male mice were immunized with different formulation of oral Prophylactic-therapeutic CUPE and/or intraperitoneal doxorubicin and then were monitored for weight gain, food intake and tumor size throughout the study. On the 32nd day after tumor injection, inflammatory cytokines levels, IL6, TNF-α and IL-1β were evaluated by Enzyme-linked Immunosorbent Assay (ELISA) and Malondialdehyde- Thiobarbituric acid (MDA) levels were measured by standard method. Results; Oral administration of CUPE in both prophylactic and therapeutic formulation to C26 adenocarcinoma bearing mice reduced the weight loss, tumor volume, and serum MDA levels compared with untreated tumor-bearing mice and Doxorubicin (Dox) groups. Also, the combination therapy of (CUPE + Dox) leads to reducing the levels of serum IL-6, TNF-α, IL-1β and tumor volume compared with untreated tumor-bearing mice and Dox groups. Serum MDA levels were considerably reduced by combination therapy of (CUPE + Dox) compared with Dox groups. Conclusions; These findings confirm the safety and efficacy of CUPE on C26 adenocarcinoma bearing mice as pure and adjuvant therapy, the results of which might be used in further human studies as a valuable natural anticancer agent alone or in combination with chemotherapy. Also the results showed that simultaneous application of CUPE and Dox leads to significant reduction of cachexia from the Dox chemotherapy., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Toxoplasmosis is a worldwide health problem that caused by intracellular apicomplexan parasite, Toxoplasma gondii (T. gondii). Considering that the available drugs for toxoplasmosis have serious host toxicity, the aim of the current study was to survey the in vitro and in vivo anti-Toxoplasma activity of Zea mays (Z. mays) and Eryngium caucasicum (E. caucasicum) extracts., Methods: Four concentrations (5, 10, 25, and 50 mg mL -1 ) of Z. mays and E. caucasicum methanolic extracts for 30, 60, 120, and 180 min were incubated with infected macrophages and then the viability of RH strain of T. gondii tachyzoites was evaluated by trypan blue staining method. Also, we evaluated the survival rate of acutely infected mice with the extracts (100 and 200 mg kg -1 day -1 ) intraperitoneally for 5 days after infection with 2× 104 tachyzoites of T. gondii., Results: The anti-Toxoplasma effect of the methanolic extracts were extremely significant compared to the negative control group in all exposure times (P < 0.05). The Z. mays (10, 25 and 50 mg mL -1 ) killed 100% of the parasites after 180 and 120 min exposure, respectively. Also, high toxoplasmacidal activity was observed with E. caucasicum extract. Furthermore, treatment of experimentally infected mice with the Z. mays (100, 200 mg kg -1 day -1 ) and E. caucasicum (100 mg kg -1 day -1 ) significantly increased their survival rate compared to untreated infected control (P < 0.05)., Conclusion: These extracts are promising candidates for further medicine development on toxoplasmosis. However, further investigations are necessary to clarify effective fractions of the Z. mays and E. caucasicum extracts and the mechanisms of action., Competing Interests: Conflict of interest There is no conflict of interests., (© 2019 Korean Pharmacopuncture Institute.)

Medicinal plants, as new drugs, are considered for treatment of insomnia, anxiety, depression, confusion, nausea, and vomiting symptoms. The current study aimed to evaluate the neuroprotective and antiemetic effects of Albizia. julibrissin Durazz. flower extract in the chickens. Emesis was induced by copper sulfate and ipecac (60 and 600 mg/kg, orally, respectively) and the methanolic extract (50, 100, and 200 mg/kg) were injected intraperitoneally (i.p.). Mitochondrial function, lipid peroxidation (LPO), protein carbonyl (PC) content, and catalase activity as biomarkers of oxidative damage were evaluated in the brain mitochondria. All doses of extract showed significant (p < 0.001) antiemetic activity against induced emesis by copper sulfate and ipecac. Brain mitochondria function (by 50, 100, and 200 mg/kg of extract) were increased 48%, 85%, and 90% against emesis induced by ipecac and 32%, 18%, and 24% against emesis induced by copper sulfate, respectively. LPO and PC contents were significantly decreased after the administration of extract in emesis induced by copper sulfate and ipecac. A significant decrease (p < 0.01) of CAT activity was observed in the extract (200 mg/kg) group in emesis induced by copper sulfate in chickens brain mitochondria. The present study suggests that the extract had antiemetic effects against emesis induced by copper sulfate and ipecac in young chickens via peripheral and central mechanisms. Neuroprotective effect of the extract could be due to the increase in bioactive compounds, plasma antioxidants, or direct free radical scavenging that could prevent lipid and protein alteration and impede the formation of oxidative damage.

Background: Green synthesis of silver nanoparticles (AgNPs) is limited to produce AgNPs with only relatively low concentrations, and is unsuitable for large-scale productions. The use of Myrtus communis (MC) leaf methanolic extract (rich in hydrolyzable tannins) has been recommended to resolve the issues related to the aggregation of nanoparticles at high concentrations of silver ions with added facet of antioxidant properties., Methods: The produced highly concentrated MC-AgNPs were characterized by using imaging and spectroscopic methods. Subsequently, antioxidant, anticancer and antifungal activities of the nanoparticles were evaluated., Results: The thermogravimetric analysis and energy dispersive spectroscopy quantitative results suggested that the nanoparticles are biphasic in nature (bio-molecule + Ag0) and layered in structure, suggesting the formation of nanoparticles through a different mechanism than those described in the literature. MC-AgNPs showed greater scavenging activity of nitric oxide and iron (II) chelating ability than the extract. It also showed good reducing power compared to the standard antioxidant. Remarkable anticancer activity of MC-AgNPs (IC50 = 5.99µg/mL) was found against HCT-116 (human colon carcinoma) cell lines after 24h exposure with a therapeutic index value 2-fold higher than the therapeutic index of standard doxorubicin. Furthermore, distinct antifungal activity (MIC = 4µg/mL) was found against Candida krusei., Conclusion: The current method outperforms the existing methods because it produces a large amount of multifunctional nanoscale hybrid materials more efficiently using natural sources; thus, it may be used for diverse biomedical applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Multiple sclerosis is a complex autoimmune disorder which characterized by demyelination and axonal loss in the central nervous system (CNS). Several evidences indicate that some new drugs and stem cell therapy have opened a new horizon for multiple sclerosis treatment, but current therapies are partially effective or not safe in the long term. Recently, herbal therapies represent a promising therapeutic approach for multiple sclerosis disease. Here, we consider the potential benefits of some herbal compounds on different aspects of multiple sclerosis disease. The medicinal plants and their derivatives; Ginkgo biloba, Zingiber officinale, Curcuma longa, Hypericum perforatum, Valeriana officinalis, Vaccinium macrocarpon, Nigella sativa,Piper methysticum, Crocus sativus, Panax ginseng, Boswellia papyrifera, Vitis vinifera, Gastrodia elata, Camellia sinensis, Oenothera biennis, MS14 and Cannabis sativa have been informed to have several therapeutic effects in MS patients.

Background: Portulaca oleracea , known as Purslane, is an annual growing herb with wide distribution around the world and traditionally used to manage several diseases. Different therapeutic properties as an anti-fever agent as well as anti-inflammatory and analgesic effects have been attributed to P. oleracea . The aim of this study was to investigate the effects of P. oleracea aerial extract on production of pro- and anti-inflammatory cytokines by human peripheral blood mononuclear cells (PBMCs). Methods: Aerial parts of P. oleracea (stems and leaves) were collected and extracted by percolation using methanol. The optimal and non-cytotoxic dose of hydro-alcoholic extract for cell culture analysis was determined by MTT assay. To assess the antiinflammatory effects of P. oleracea , PBMCs obtained from 12 normal volunteers were cultured in RPMI complete medium and cotreated with E. coli lipopolysaccharide (LPS) and P. oleracea hydro-alcoholic extract. Following 18-hour incubation, culture supernatants were harvested for measurement of secreted TNF-α, IL-6 and IL-10 by ELISA. Statistical analyses were performed using the SPSS v.20, and data analyzed by Kolmogorov-Smirnov, Mann-Whitney U, Kruskal-Wallis and post Hoc tests. P-values<0.05 were considered significant. Results: The optimal non-cytotoxic concentration of P. oleracea aerial extract was defined as 100 μg/ml based on MTT viability assay. P. oleracea hydro-alcoholic extract significantly decreased the concentration of both pro-inflammatory cytokines TNF-α and IL-6 in LPS-stimulated PBMCs (p<0.001 and p<0.001, respectively). However, the concentration of IL-10 as an anti-inflammatory cytokine, did not show any statistically significant change (p=0.390). Conclusion: Our findings highlighted the potential anti-inflammatory properties of P. oleracea in herbal medicine. Future analysis on different constituents of total extract may confirm its therapeutic effects as a promising anti-inflammatory compound.

Toxoplasmosis is a worldwide disease caused by the protozoan parasite Toxoplasma gondii (T. gondii), which is most commonly treated by pyrimethamine and sulfadiazine. However, this treatment presents several adverse side effects; Thus, new drugs with lower toxicities are urgently needed. In this study the anti-T. gondii activity of A. vera and Eucalyptus extracts were evaluated in vitro using a MTT (3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide) assay and in vivo by measuring the survival rates of mice infected with 2 × 10 3 tachyzoites of RH strain of T. gondii and then injected intraperitoneally by different concentrations of extracts for 4 days. Biochemical parameters such as Ferric Reducing Antioxidant Potential (FRAP) and malondialdehyde (MDA) assay were also evaluated. As results, in the in vitro assay, the IC 50 values were 13.2, 24.7, 2.63 μg/ml, and the selectivity indexes were 3.3, 2.4, 3.03 for the A. vera, Eucalyptus and pyrimethamine, respectively. The mice treated with Eucalyptus showed a better survival rate than others (P < 0.05). The increased weight of liver and spleen, due to infection, was reduced by treatments. In FRAP assay Eucalyptus showed a better antioxidant activity than the other extracts. MDA levels in both liver and spleen were reduced by treatment. The results show that A. Vera and Eucalyptus possess anti-T. gondii activities in vitro and in vivo, in addition, Eucalyptus shows antioxidant activity with a higher survival rate. Therefore, Eucalyptus may be a useful candidate for treating Toxoplasma infection. Moreover, further studies are required to investigate the fractionations of this plant against T. gondii., (Copyright © 2018. Published by Elsevier Inc.)