VEGF/VEGFR axis and its signaling in melanoma: Current knowledge toward therapeutic targeting agents and future perspectives.

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.

Chlorogenic Acid Derivatives: Structural Modifications, Drug Design, and Biological Activities: A Review.

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, PubMed 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.

Drug design strategies that aim to improve the low solubility and poor bioavailability conundrum in quercetin derivatives.

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.

In Vitro and In Vivo Anti-parasitic Activity of Sambucus ebulus and Feijoa sellowiana Extracts Silver Nanoparticles on Toxoplasma gondii Tachyzoites.

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.

The Role of MexCD-OprJ and MexEF-OprN Efflux Systems in the Multiple Antibiotic Resistance of Pseudomonas aeruginosa Isolated from Clinical Samples.

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.

Sida rhombifolia Exerts Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer HepG2 Cells in Vitro.

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.

Topical administration of Juglans regia L. leaf extract accelerates diabetic wound healing.

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-ß 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-1ß 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.

A Highly Sensitive and Selective Quinazoline-Based Colorimetric Probe for Naked-Eye Detection of Fe3+ Ions.

A novel quinazoline-based colorimetric sensor (probe 1) that detected Fe3+ via naked-eye in a buffered MeOH: H2O (8:2) solvent system within a neutral pH range was synthesized and its structure was confirmed by 1H-NMR, 13C-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 Fe3+ ions among various other ions. The competitive effect indicated relatively low interference of other cations on the interaction of probe 1/Fe3+. 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 Fe3+, the absorption of probe1 reached saturation, and the reaction was completed. The effect of pH on the absorption and stability of probe 1 towards Fe3+ was examined. The pH range from 5.0 to 9.0 was appropriate for detection of Fe3+. To find the binding stoichiometric of the complex, Job's plot studies were carried out by varying the molar ratio of Fe3+. A 1:2 binding ratio was proposed. Under the optimal conditions, a good linear relationship (R2 = 0.9886) was at the concentration of Fe3+ 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 Fe3+ in samples of urine with high recovery.

The effects of Feijoa sellowiana fruit extract on wound healing in rats: a stereological and molecular study.

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)-ß 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.

Naked Eye Chemosensor and In Vivo Chelating Activity of Iron (III) By Bromopyridine Quinoxaline (BPQ).

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 Fe3+ 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 Fe3+ (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 Fe3+) 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.

Evaluation of Alterations in DNA Methylation of CYP3A4 Gene Upstream Regulatory Elements in Gastric Cancer and in Response to Diazinon Treatment.

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.

Vascular Endothelial Growth Factor Receptors [VEGFR] as Target in Breast Cancer Treatment: Current Status in Preclinical and Clinical Studies and Future Directions.

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.

CYP1A1 contiguous hypermethylation within a putative CpG block is associated with breast cancer progression: Feasibility to define boundary motives.

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.

Pyridine-2-yl Quinoxaline (2-CPQ) Derivative As a Novel Pink Fluorophore: Synthesis, and Chemiluminescence Characteristics.

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 1H, 13C 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 (фF = 0.21). Hence, the fluorophore was applied in the peroxyoxalate chemiluminescence system. The reaction of imidazole, H2O2, 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.

O-Glycoside quercetin derivatives: Biological activities, mechanisms of action, and structure-activity relationship for drug design, a review.

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.

Quercetin derivatives: Drug design, development, and biological activities, a review.

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.

Hemoglobin F (HbF) Inducers; History, Structure and Efficacies.

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 ß-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 ß-globin gene promoters were applied during the researches. (d) New natural products and lead compounds were found based on various studies as HbF inducers.

Stereological and molecular studies on the effects of Ferula persica extract on wound healing in rats.

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-ß 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.

Protective effects of rutin and chlorogenic acid against antihypoxic conditions in mice.

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.