Danijela Mišić

University of Belgrade · Institute for Biological Research Sinisa Stankovic

Introduction Nepeta species contain a variety of secondary metabolites, including iridoid monoterpenes – nepetalactones and phenolic acids – that are considered the main bioactive constituents. This work represents the first attempt to comparatively explore variations in these two major groups of secondary metabolites within the genus. Objective T...

Methanol extracts of aerial parts and roots of five centaury species (Centaurium erythraea, C. tenuiflorum, C. littorale ssp. uliginosum, C. pulchellum, and Schenkia spicata) were analysed for their main secondary metabolites: secoiridoid glycosides, a group of monoterpenoid compounds, and phenolics (xanthones and flavonoids), and further investiga...

Species within the genus Centaurium readily hybridize and polyploid complexes are often seen in natural populations. We describe phytochemical profiles of newly discovered allohexaploid hybrid, here named Centaurium pannonicum, and its parental tetraploid species C. erythraea and rare C. littorale ssp. compressum. Our aim was to examine chemodivers...

The medicinal plants Salvia officinalis, Trifolium pratense, Agrimonia eupatoria, Cichorium intybus and Vinca minor are traditionally used for the prevention and treatment of numerous diseases, including diabetes. Type 2 diabetes (T2D) is one of the most common diseases nowadays, often accompanied by oxidative stress and microbial infections. The a...

Nepeta nuda L. is a medicinal plant enriched with secondary metabolites serving to attract pollinators and deter herbivores. Phenolics and iridoids of N. nuda have been extensively investigated because of their beneficial impacts on human health. This study explores the chemical profiles of in vitro shoots and wild-grown N. nuda plants (flowers and...

Introduction: The endemic species Nepeta cyrenaica Quézel & Zaffran, native to northeastern Libya, is valued as an important honey-bearing plant. Objectives: This study was aimed to examine the micromorphology, phytochemistry, and bioactivity of in vitro-propagated N. cyrenaica for the first time. Materials and methods: The leaf indumentum was...

The same population of the polytrichaceous moss Polytrichum formosum was studied over four different periods of the year, analysing its carbohydrate and polyphenolic content and dynamics related to environmental seasonal changes. A total of 18 different types of sugars (including mono-, di-, tri- and tetra-saccharides) and four sugar alcohols were...

Maize is important to global food security, being one of the predominant cereals in human and domesticated livestock diets worldwide. Due to the increasing human population, it will be important to not only design cropping systems to increase maize yield and sustainability but also to improve the nutritional quality of maize edible tissues. To dete...

The aim of this study was to determine intra- and interspecies variation in the qualitative and quantitative composition of methanol-soluble metabolites in the leaves of three Digitalis species (D. lanata, D. ferruginea, and D. grandiflora) from the central Balkans. Despite the steady use of foxglove constituents for human health as valuable medici...

The response to salt stress analysed by quantitative and qualitative analyses in three selected moss species was studied. Non-halophytic funaroid Physcomitrium patens and two halophytic mosses, funaroid Entosthodon hungaricus and pottioid Hennediella heimii were exposed to salt stress under controlled in vitro conditions. The results clearly showed...

Spiked centaury (Centaurium spicatum) is a well-known medicinal plant from the Mediterranean region with various bioactivities, but there are no studies addressing the use of different solvent systems to improve its pharmacological potential. Nine extraction procedures were adapted to study the effects of solvent composition on the content of bioac...

The present study provides, for the first time, a physicochemical and biochemical characterization of the redox processes associated with the ripening of Solanum dulcamara L. (bittersweet) berries. Electron Paramagnetic Resonance Spectroscopy (EPRS) and Imaging (EPRI) measurements of reactive oxygen species (ROS) were performed in parallel with the...

Rabelera holostea (L.) M. T. Sharples & E. A. Tripp (Greater Stitchwort), formerly known as Stellaria holostea L., is widespread in the warm temperate areas of Europe and Western Asia, the Caucasus region, as well as in some countries of North Africa. Nowadays it is considered as a weed, but earlier it was often used raw in salads or for the treatm...

The genus Salvia is well-known for its use in food as aromatic and spicy herbs, as well as in the pharmaceutical and fragrance industries. Regardless of their importance, some Salvia species have not been thoroughly examined and chemically characterized, including Salvia pratensis L. In the present study, the detailed phenolic composition using LC/...

Centaurium erythraea, used as medical plant from the earliest times, is an immense depot of quite rare bioactive compounds. Secoiridoids (sweroside, swertiamarin, and gentiopicrin) and xanthones (methylbellidifolin and decussatin) are predominant bioactive compounds in C. erythraea. The present study aims at providing new insights into how the cont...

Secoiridoid glucosides (SGs) are monoterpenoids derived from the iridoid cyclopentan-C-pyran skeleton with B-D glucose linked at C1 position. Coordinated metabolic processes, such as biosynthesis and catabolism of SGs, ensure constitutive presence of these bitter tasting compounds in plant tissues, which plays a decisive role in the defence against...

Nepeta nuda (catmint; Lamiaceae) is a perennial medicinal plant with a wide geographic distribution in Europe and Asia. This study first characterized the taxonomic position of N. nuda using DNA barcoding technology. Since medicinal plants are rich in secondary metabolites contributing to their adaptive immune response, we explored the N. nuda meta...

Cistus creticus subsp. creticus is a shrubby Mediterranean plant used since ancient times in folk medicine for the treatment of different diseases. C. creticus extracts and resin contain different types of secondary metabolites, such as terpenoids (predominantly labdane type diterpenoids), and phenylpropanoids. Growth conditions seem to influence t...

The aim of this study is to use a comparative analysis of the ecology of invasive species Ailanthus altissima (Mill.) Swingle, Amoprha fruticosa L. and Robinia pseudoacacia L. to assess the possibilities and risks of their application in the soil and vegetation restoration in different anthropogenically modified habitats. The results of the compara...

The use of medicinal herbs can mitigate oxidative stress-induced diabetic complications and organ failure. This study investigated hepato- and reno-protective effects of methanol extract of Centaurium erythraea Rafn (CEE) in STZ-diabetic rats pre-treated (2 weeks) and/or post-treated (4 weeks) with CEE (orally, 100 mg/kg/day). Both CEE treatments m...

The following study was designed to explore antimicrobial properties of the by-product obtained in a hydro-distillation process of essential oil from Nepeta nuda L. Based on the obtained decoction of N. nuda and apple juice, we strived to develop a novel drink that would have antimicrobial self-preserving properties. By using 96-well plate microdil...

The following study was designed to explore antimicrobial properties of the by-product obtained in a hydro-distillation process of essential oil from Nepeta nuda L. We strived to develop a novel drink with antimicrobial self-preserving properties based on two components, N. nuda decoct and apple juice. By using 96-well plate microdilution assay it...

Artemisia absinthium L. (Asteraceae) is traditionally used for gastrointestinal ailments and disorders linked to numerous risk factors including microbial infections. We aimed to provide contemporary evidence for its ethnopharmacological use and determine its antimicrobial capacity and mode of action, cytotoxicity, and phenolic constituents. Ethnop...

A plant’s main mechanism to diminish the effects caused by high free radical levels generated during high irradiance is the synthesis of various secondary metabolites. In addition to interspecies differences, their concentrations may be influenced by genetic, ontogenic, morphogenetic or environmental factors. We investigated the influence of geneti...

Two Balkan Peninsula endemics, Nepeta rtanjensis and N. argolica subsp. argolica, both characterized by specialized metabolite profiles predominated by iridoids and phenolics, are differentiated according to the stereochemistry of major iridoid aglycone nepetalactone (NL). For the first time, the present study provides a comparative analysis of ant...

Cistus creticus L. subsp. creticus (rockrose) is a shrub widespread in Greece and the Mediterranean basin and has been used in traditional medicine as herb tea for colds, for healing and digestive hitches, for the treatment of maladies, as perfumes, and for other purposes. Compounds from its flavonoid fraction have recently drawn attention due to a...

Phosphinothricin (PPT) is one of the most widely used herbicides. PTT targets glutamine synthetase (GS) activity in plants, and its phytotoxicity is ascribed to ammonium accumulation and reactive oxygen species bursts, which drives rapid lipid peroxidation of cell membranes. In agricultural fields, PPT is extensively sprayed on plant foliage; howev...

The genus Nepeta is one of the largest genera in the Lamiaceae family, and Iran is one of the main centers of origin of this genus. The genetic diversity estimation of the genus Nepeta germplasm provides a basis for future biodiversity conservation efforts and also for the selection of high-productive genotype(s) for the field production improvemen...

Extracts of the aerial (fronds) and underground parts (rhizome and roots) of Asplenium adiantum-nigrum L. and Asplenium ruta-muraria L. were analyzed for their phenolic composition and antioxidant properties (scavenging capacities against DPPH• and ABTS•⁺), and were comparatively assayed for antimicrobial and antibiofilm activity. Total of the 17 p...

A number of Nepeta species (fam. Lamiaceae) are interesting medicinal crops for arid and semi-arid areas, due to their ability to maintain essential developmental and physiological processes and to rationalize their specialized metabolism under water deficit growth conditions. The present research is, to our knowledge, the first attempt to investig...

Blackstonia perfoliata (L.) Huds. is known as a highly bitter secoiridoid glycosides-containing plant and as a possible substitute for some Gentianaceae plants in herbal preparations. Nevertheless, its bioactive properties are still unknown. The present study aimed to characterize both, secoiridoid glycosides and phenolic constituents, and to inves...

Oxidative stress is one of the major mechanisms that underlies the damage of pancreatic β- cells and defects in insulin secretion in diabetes. As herbal preparations can alleviate oxidative stress through their redox-active secondary metabolites, in this study we investigated the cytoprotective effects of Centaurium erythraea extract (CEe) against...

This study was designed to evaluate the possible effect of methanol extracts of aerial parts and roots of Alchemilla vulgaris L. (AVA and AVR, respectively) in preventing cisplatin-induced hepatorenal and testicular toxicity in rats. UHPLC/DAD/(−)HESI-MS/MS analysis was performed to determine the detailed phenolic profile of AVA and AVR. The male W...

The impact of ploidy level on both the regenerative potential under in vitro conditions and the production of major bioactive specialized metabolites, such as iridoids and xanthones, was examined in Centaurium erythraea Rafn. Shoot regeneration frequency was genotype dependent, but not affected by explant ploidy level. In most cases, the regenerate...

Centaurium erythraea Rafn produces and accumulates various biologically active specialized metabolites, including secoiridoid glucosides (SGs), which help plants to cope with unfavorable environmental conditions. Specialized metabolism is commonly modulated in a way to increase the level of protective metabolites, such as SGs. Here, we report the m...

Interspecific hybridization is one of the major actuators of evolutionary changes in plants. As the result of allopolyploid hybridization, offspring may gain different ploidy levels in comparison to parental species, which can provide them instant reproductive isolation. Two tetraploid sister species, Centaurium erythraea and C. littorale, readily...

Ethnopharmacological relevance: Centaurium erythraea Rafn (CE) is used as a traditional medicinal plant in Serbia to treat different ailments due to its antidiabetic, antipyretic, antiflatulent and detoxification effects. Aim of the study: Elucidation of the mechanisms that underlie the antioxidant and pro-survival effects of the CE extract (CEE...

Active ingredient of the commercial herbicide BASTA (B), phosphinothricin, acts as an inhibitor of glutamine synthetase (GS), a key enzyme in ammonium assimilation. The treatment with BASTA leads to an elevation of ammonium levels in plants and further to various physiological alterations, ammonium toxicity and lethality. Results of the present stu...

Allelopathic plants exploit their chemical 'weapons' to prevail over the competition, suppress neighboring plants and consequently use the available resources more efficiently. However, the investigation of plant allelopathic interactions in rhizosphere is difficult to perform because of its high complexity due to interactions of biotic and abiotic...

Available scientific literature reports very few microsatellite markers derived from tetraploid genomes using de novo transcriptome sequencing, mostly because their gain usually represents a major computational challenge due to complicated combinatorics during assembly of sequence reads. Here we present a novel approach for mining polymorphic micro...

While bioactive properties of Centaurium erythraea Rafn secoiridoid glucosides (SG) are widely recognized, many aspects related to their biochemistry, metabolism and relationship to the overall plant physiology are not yet understood. Here we present for the first time an insight into the molecular background of organ-specific and genotype-dependen...

Phosphinothricin, active ingredient of the commercial herbicide BASTA, acts as an inhibitor of glutamine synthetase (GS), a key enzyme in ammonium assimilation, which leads to the elevation of ammonium levels in plants and further to various physiological alternations, ammonium toxicity and lethality. Nepeta rtanjensis Diklić & Milojević essential...

The present study describes the interactive effects of BASTA and Nepeta rtanjensis essential oil (NrEO), two agents showing differential mode of herbicidal action, on Arabidopsis thaliana antioxidant system. BASTA is known to act through inhibiting glutamine synthetase activity and inducing ammonium accumulation and toxicity, while NrEO and its maj...

Common centaury (Centaurium erythraeaRafn) is rich in secoiridoid glucosides (SG’s): sweroside, swertiamarin and gentiopicrin. These glycosides are believed to be a part of dual defense system in which the SG’s are bio-activated by hydrolytic enzymes. Upon tissue disruption, SG’s are released from storage compartments and hydrolyzed via β-glucosida...

Plant species Centaurium erythraeaRafn (fam. Gentianaceae) is characterized by the presence of secoiridoid glucosides (SGs) as dominant secondary metabolites. The SG biosynthetic pathway has not yet been fully elucidated, despite the great pharmacological importance of this species. Here, an insight into the SG biosynthesis is achieved by comparing...

Major constituents of Nepeta rtanjensisDiklić & Milojević: trans,cis-nepetalactone and its dehydrogenation product dehydronepetalactone, are synthetized and accumulated in glandular trichomes. Interestingly, dehydronepetalactone is the major monoterpenoid in fresh leaves of N. rtanjensis, while the amount of this compound dramatically decreases in...

Centaurium erythraea(centaury), a plant with a long tradition of medicinal use, contains bioactive secoiridoid glucosides (SGs). The exogenous application of methyl jasmonate (MeJA) may elicit a response similar to stress, and is used in the present study to induce SG accumulation and expression of SGs’ biosynthesis associated genes in centaury’s a...

The aim of our study was to examine the potential ameliorating effect of the methanolic extract of Satureja hortensis L. (summer savory) aerial parts against cisplatin-induced oxidative damage in renal, hepatic, and testicular tissues. S. hortensis methanol extract at the doses of 50, 100 and 200 mg/kg of body weight were orally administered to Wis...

Nepetalactones are accumulated as the main secondary metabolites in the majority of Nepeta species; however, their biosynthetic pathway remains to a great extent unknown, as well as their relationship to the overall physiology of these plants. Nepetalactones most certainly arise through general iridoid biosynthetic pathway leading to nepetalactol,...

Abstract The present study was principally aimed at ascertaining the differences in metabolomics profiles and biological activities between non-hydrolyzed (ME) and hydrolyzed methanol extract (HME) of Centaurium erythraea Rafn. UHPLC–MS/MS Orbitrap analysis showed that the enzymatic hydrolysis of the extract caused changes in β-d-glycoside/aglycone...

Methanol extracts of three endemic Nepeta species were analyzed for their main secondary metabolites, terpenes and phenolics, and further investigated for antioxidant capacity and embryonic toxicity in zebrafish. UHPLC/DAD/(±) HESI-MS/MS analysis showed that the dominant compound in N. rtanjensis was trans,cis-nepetalactone, the cis,trans isomer of...

Asplenium ceterach L. (syn. Ceterach officinarum Willd.) or rustyback fern is a plant species traditionally used in Mediterranean countries as an expectorant, diuretic, against spleen complaints, kidney stones and hemorrhoids. Phytochemical analysis of gametophytes and sporophytes of A. ceterach was performed, followed by comparative analysis of ph...

Cucumber (Cucumis sativus) fruit has been used in cuisine worldwide, while its leaves are rich in immunomodulatory compounds. Cucumber leaf extract (CLE) was characterized by the predominance of triterpenoids cucurbitacins and significant levels of phenolics. Effects of CLE on CD4⁺ T helper (Th) cells and macrophages, as the major encephalitogenic...

Nepeta rtanjensis Diklić & Milojević (fam. Lamiaceae) is an endemic, critically endangered plant, protected by the law in Serbia. Various biological activities have been ascribed to its major constituents, nepetalactones. In this study we describe for the first time cytotoxic activity of N. rtanjensis essential oil (EO), obtained from field cultiva...