Effects of Methyl Jasmonate and Putrescine on Tryptanthrin and Indirubin Production in in vitro Cultures of Isatis demiriziana Mısırdalı

Tryptantrin and indirubin are pharmacologically active compounds used in treatment of disseases such as cancer and Alzheimer's. In this study, we investigated the influences of different concentrations of methyl jasmonate (MeJa) and putrescine (Put) on tryptanthrin and indirubin production in leaf explants and development of Isatis demiriziana Mısırdalı grown in vitro. In all media treated with methyl jasmonate, tryptanthrin production in leaves of plantlets showed an increase. The highest increase in tryptanthrin production was observed in solid Murashige-Skoog (MS) medium containing 1.0 mM MeJa (154.026 ± 0.11 µg g-1), about 2.85-fold higher than the control (untreated plantlets) (40.017 ± 0.031 µg g-1). Production of tryptanthrin decreased about 2.56-fold in the leaves of plantlets treated with Put, when compared to control. The highest indirubin production was obtained in the leaves of plantlets grown in the MS medium containing 0.1 mM MeJa (11.274 ± 0.035 µg g-1) but treatments with Put didn’t show any positive affect on the indirubin production. Analysis of tryptanthrin and indirubin were performed using high performance liquid chromatography (HPLC)

Effect of Silver Nanoparticles on Production of Indole Alkaloids in Isatis constricta

Silver nanoparticles (AgNPs) are widely used in many applications of biotechnology, including medicine and agriculture. They are released to the nature as waste materials, which can cause physiological and biochemical effects on plants. Indigo, indirubin and tryptanthrin are valuable indole alkaloid compounds in Isatis constricta due to both medicinal effects and dye properties. This research was conducted to determine the effects of different concentrations (0, 0.25, 0.5, 1, 1.5 and 2 mg L-1) of AgNPs on the production of indigo, indirubin and tryptanthrin compounds in leaves of in vitro grown shoots of I. constricta Davis. Indigo production was 1.15-fold of control (869 +/- 8.33 mu g g(-1)) in the leaves of shoots regenerated in Murashige and Skoog supplemented with 2 mg L-1 of AgNPs (1003 +/- 11.42 mu g g(-1)) on 5 days post-treatment. Tryptanthrin production showed an increase in all applications of AgNPs, but the highest increase was observed at a concentration of 2 mg L-1 (4.59 +/- 0.046 mu g g(-1)) and this increase was 1.71-fold of control (2.68 +/- 0.031 mu g g(-1)) on 5 days post-treatment. The production of indigo and tryptanthrin decreased on 10 and 15 days post-treatment with AgNPs. The contents of indirubin decreased during day 5-10-15 and at all concentrations of AgNPs compared to the control

Qualitative and Quantitative Determination of Tryptanthrin, Indirubin, Indican and Isatin Indole Alkaloids During Vegetative and Flowering Stages in the Roots and Leaves of Isatis constricta P. H. Davis

Isatis genus more known as the indigo plant is a plant belonging to the Brassicaceae family in Turkey. Turkey has 31 types and 15 subtypes in various provinces.18 of these species and 3 of the subspecies are assumed as endemic. All taxa of the genus are extensively used in dyeing and treatment of various infections. They contain large number of secondary compounds like phenolics, flavonoids and alkaloids in root, leaf, flower and fruit parts. Among these indole alkaloids like triptanthrin, indirubin, indican and isatin are used in treatment of many diseases. These are obtained from the leaves and roots are pharmacologically active compounds. This study revealed that this biannual herbaceous plant grows 30 - 50 cm in length on volcanic slopes, at 1200 - 1300 meters above sea level. It generally grows in Eastern Anatolia and the Mediterranean region of Turkey. The study aimed to determine optimum ontogenetic stage of Isatis constricta to extract natural bio compounds like indirubin, isatin, indican, tryptanthrin. The leaf and root samples used in this study were collected from Maden county of Elazığ province. They were tested for the presence of these compounds during vegetative and flowering period of the plant. The HPLC (HighPerformance Liquid Chromatography) analysis results showed that tryptanthrin 0.482 (±0.0072) µg/g and indirubin 0.029 (±0.00007) μg/g has the highest concentrations in the leaf samples obtained during the vegetative period. However, isatin 4.358 (± 0.0985) μg/g and indican 21.330 (± 0.114) μg/g were found to have the highest concentration in leaf samples obtained during flowering period. When both results are compared, it can be seen that the amount of tryptanthrin, isatin, indirubin and indican alkaloids were found in the leaves of I. constricta higher than to the roots. This research idicate that the most appropriate development stage of I. constricta to obtain triptanthrin indirubin, indican and isatin compounds

Contents of phenolic and flavonoid compounds in Isatis demiriziana Mısırdalı: an endemic to the Southeast

Isatis demiriziana Mısırdalı plant contains a number of compounds which has anticarcinogenic, antioxidant and other preventive effects. In this study, the flavonoid and phenolic contents in the plant samples harvested in the vegetative (leaf and root) and full flowering season (flower, leaf and root) were determined by LC-MS/MS. Among the 27 compounds studied, malic acid was found to be the most abundant compound in the methanolic extracts of samples and the amount of malic acid of vegetative root extracts were the highest (30124,37 µg g-1 dry-extract). Moreover, it was also determined considerable amount of salicylic acids and p-coumaric in the root extracts. This study is the first detailed study on the phenolic and flavonoid compounds of I. demiriziana. Based on the findings of this study, in further researches might be refered as an additional source in production of phenolic and flavonoid compounds

Novel SNARE Complex Polymorphisms Associated with Multiple Sclerosis: Signs of Synaptopathy in Multiple Sclerosis

Background: It is well known that axonal degeneration plays a role in disability in patients with multiple sclerosis, and synaptopathy has recently become an important issue.Aims: To investigate the possible roles of selected synaptic and presynaptic membrane protein genetic polymorphisms (VAMP2, SNAP-25, synaptotagmin, and syntaxin 1A) in patients with multiple sclerosis.Study Design: Case-control study.Methods: A total of 123 patients with multiple sclerosis and 192 healthy controls were included. The functional polymorphisms of specific SNARE complex proteins (VAMP2, synaptotagmin XI, syntaxin 1A, and SNAP-25) were analyzed by polymerase chain reaction.Results: Significant differences were detected in the genotype and allele distribution of 26-bp Ins/Del polymorphisms of VAMP2 between patients with multiple sclerosis and control subjects; Del/Del genotype and Del allele of VAMP2 were more frequent in patients with multiple sclerosis (p=0.011 and p=0.004, respectively). Similarly, Ddel polymorphism of SNAP-25 gene C/C genotype (p=0.059), syntaxin 1A T/C and C/C genotypes (p=0.005), and synaptotagmin XI gene C allele (p=0.001) were observed more frequently in patients with multiple sclerosis. CC, syntaxin rs1569061 1A gene for 33-bp promoter region TC haplotypes, and synaptotagmin XI gene were found to be associated with an increased risk for multiple sclerosis (p=0.012). Similarly, GC haplotype for rs3746544 of SNAP-25 gene and rs1051312 of SNAP-25 gene were associated with an increased risk for multiple sclerosis (p=0.022).Conclusion: Genetic polymorphisms of SNARE complex proteins, which have critical roles in synaptic structure and communication, may play a role in the development of multiple sclerosis

Distinct apoptotic blocks mediate resistance to panHER inhibitors in HER2+breast cancer cells

Despite the development of novel targeted therapies, de novo or acquired chemoresistance remains a significant factor for treatment failure in breast cancer therapeutics. Neratinib and dacomitinib are irreversible panHER inhibitors, which block their autophosphorylation and downstream signaling. Moreover, neratinib and dacomitinib have been shown to activate cell death in HER2-overexpressing cell lines. Here we showed that increased MCL1 and decreased BIM and PUMA mediated resistance to neratinib in ZR-75-30 and SKBR3 cells while increased BCL-XL and BCL-2 and decreased BIM and PUMA promoted neratinib resistance in BT474 cells. Cells were also cross-resistant to dacomitinib. BH3 profiles of HER2 + breast cancer cells efficiently predicted antiapoptotic protein dependence and development of resistance to panHER inhibitors. Reactivation of ERK1/2 was primarily responsible for acquired resistance in SKBR3 and ZR-75-30 cells. Adding specific ERK1/2 inhibitor SCH772984 to neratinib or dacomitinib led to increased apoptotic response in neratinib-resistant SKBR3 and ZR75-30 cells, but we did not detect a similar response in neratinib-resistant BT474 cells. Accordingly, suppression of BCL-2/BCL-XL by ABT-737 was required in addition to ERK1/2 inhibition for neratinib- or dacomitinib-induced apoptosis in neratinib-resistant BT474 cells. Our results showed that different mitochondrial apoptotic blocks mediated acquired panHER inhibitor resistance in HER2 + breast cancer cell lines as well as highlighted the potential of BH3 profiling assay in prediction of panHER inhibitor resistance in breast cancer cells

The effects of UV-C on production of hypericin, phenolic and flavonoid in Hypericum triquetrifolium Turra

The current study was undertaken to determine the effects of UV-C radiation of total hypericin, phenolic and flavonoid content in Hypericum triquetrifolium Turra. The UV-C radiation was applied to H. triquetrifolium at different periods (15, 30, 45, 60 min). The highest total hypericin, phenolic and flavonoid accumulation 292 +/- 2.8, 357 +/- 3.4 and 331 +/- 3.7 mu gg(-1) was achieved in 15 minutes of exposure to UV-C radiation when compared with the contents of control groups (140 +/- 2.3, 185 +/- 3.7, 173 +/- 2.5 mu gg(-1))