Ethnobotanical and ethnomedicinal research into medicinal plants in the Mt Stara Planina region (south-eastern Serbia, Western Balkans).

BACKGROUND: Ethnobotanical research in Southeast Europe-one of the most important European hotspots for biocultural diversity-is significant for the acquisition of Traditional Ecological Knowledge related to plants as well as for encouraging the development of local environments. The current ethnobotanical research was conducted in the region of Mt Stara Planina (south-eastern Serbia), which is characterised by rich phytodiversity with a large number of endemic and relict plant species. The aim of the study was to document the diversity of uses of medicinal plants and of traditional knowledge on their therapeutic uses. METHODS: Ethnobotanical data was collected through both open and semi-structured interviews with locals. Fifty-one inhabitants were interviewed (26 men and 25 women), aged 30-91, and data was analysed by means of use reports, citation frequency, use values (UV), and the informant consensus factor (ICF). RESULTS: The study identified 136 vascular medicinal plant taxa and one lichen species belonging to 53 families and 116 genera. Lamiaceae (19), Rosaceae (18), and Asteraceae (17) had the highest species diversity. The plant parts most commonly used to make a variety of herbal preparations were the aerial parts (54 citations), leaves (35 citations), fruits (20 citations), flowers (18 citations), and roots (16 citations), while the most common forms of preparation were teas (60.78%), consumption of fresh tubers, leaves, roots, and fructus (6.86%), compresses (5.88%), juices (5.39%), decoctions (3.92%), 'travarica' brandy (3.92%), and syrups (2.45%). Of the recorded species, 102 were administered orally, 17 topically, and 18 both orally and topically. The plants with a maximum use value (UV = 1) were Allium sativum, Allium ursinum, Gentiana asclepiadea, Gentiana cruciata, Gentiana lutea, Hypericum perforatum, Thymus serpyllum and Urtica dioica. The highest ICF value (ICF = 0.95) was recorded in the categories of Skin and Blood, Blood Forming Organs, and Immune Mechanism. CONCLUSIONS: This study shows that medicinal plants in the research area are an extremely important natural resource for the local population as they are an important component of their health culture and provide a better standard of living.

Toad zoonyms mirror the linguistic and demographic history of Greece.

The common toad (Bufo bufo) has been the subject of many folk tales and superstitions in Western Europe, and as a result, it is characterised by numerous common names (zoonyms). However, the zoonyms of the toad and its associated traditions have remained unexplored in the Balkans, one of Europe's linguistic hotspots. In the present study, it was attempted to fill this knowledge gap by focusing on Greece, where more than 7.700 individuals were interviewed both in the field and through online platforms, in order to document toad zoonyms from all varieties and dialects of Greek, as well as local non-Greek languages such as Arvanitika, South Slavic dialects, and Vlach. It was found that the academically unattested zoonyms of the toad provide an unmatched and previously unexplored linguistic and ethnographic tool, as they reflect the linguistic, demographic, and historical processes that shaped modern Greece. This is particularly pertinent in the 21st century, when a majority of the country's dialects and languages are in danger of imminent extinction-and some have already gone silent. Overall, the present study shows the significance of recording zoonyms of indigenous and threatened languages as excellent linguistic and ethnographic tools that safeguard our planet's ethnolinguistic diversity and enhance our understanding on how pre-industrial communities interacted with their local fauna. Furthermore, in contrast to all other European countries, which only possess one or only a few zoonyms for the toad, the Greek world boasts an unmatched 37 zoonyms, which attest to its role as a linguistic hotspot.

Small regions as key sources of traditional knowledge: a quantitative ethnobotanical survey in the central Balkans.

BACKGROUND: Starting from the idea that unexplored areas may yield new and different ethnobotanical information, we performed a survey of traditional uses of plants in two neighboring districts situated in east Serbia (Bor and Aleksinac), both lacking in previous ethnobotanical reports, but characterized by an interesting history and culture, together with some specific features. In this study, we hypothesized that such small and specific areas could be of high ethnobotanical importance. METHODS: Semi-structured interviews were used with 155 informants. Relative cultural importance (RCI) indices, such as the frequency of citation (FC), relative frequency of citation (RFC), relative importance index (RI), informant consensus factor (ICF-FIC), use value (UV), fidelity level (FL) and Jaccard index (JI), were calculated, and principal coordinate analysis (PCoA) was performed. RESULTS: In this study, 2333 use-reports and 114 plants were recorded. Of the 101 medical herbs, 33 are included in the European Pharmacopoeia Edition 8.0. The most frequently used mode of preparation was as an infusion (50.0%), while leaf (44.7%) was the most used plant part. The highest FC and RFC values were recorded for Hypericum perforatum L. (13.1 and 0.2, respectively), while the highest RI was documented for Urtica dioica L. (1.0). ICF and FL indices showed important differences among selected groups of informants. The PCoA showed three homogeneous plant groups. Plants were mostly used for the treatment of digestive (49.1%), circulatory (41.2%) and respiratory system disorders (35.1%). Thirty-seven (32.5%) herbs were used for human nutrition, 14 (12.3%) in veterinary medicine, 17 (14.9%) in rituals and ethnoculture, while 24 (21.0%) for miscellaneous purposes. The highest degree of similarity was determined with studies conducted in close proximity. Four species are new to Balkan ethnobotany. New uses for some well-known plants are highlighted. CONCLUSION: The study indicated that small and specific areas in the Balkans may be an important reservoir of ethnobotanical knowledge.

The genetic history of the Southern Arc: A bridge between West Asia and Europe.

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra-West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe.

Relating environmental pressures to littoral biological water quality indicators in Western Balkan lakes: Can we fill the largest gaps?

Along six transects in each of six lakes across the Western Balkans, we collected data for three groups of littoral biological water quality indicators: epilithic diatoms, macrophytes, and benthic invertebrates. We assessed the relationships between them and three environmental pressures: nutrient load (eutrophication), hydro-morphological alteration of the shoreline, and water level variation, separating the effect of individual lakes and continuous explanatory variables. Lake water total phosphorus concentration (TP) showed substantial variation but was not related to any of the tested biological indicators, nor to any of the tested pressures. We suggest that this may be due to feedback processes such as P removal in the lake littoral zone. Instead, we found that a gradient in surrounding land-use towards increasing urbanization, and a land-use-based estimate of P run-off, served as a better descriptor of eutrophication. Overall, eutrophication and water level fluctuation were most important for explaining variation in the assessed indicators, whereas shoreline hydro-morphological alteration was less important. Diatom indicators were most responsive to all three pressures, whereas macrophyte biomass and species number responded only to water level fluctuation. The Trophic Diatom Index for Lakes (TDIL) was negatively related to urbanization and wave exposure. This indicates that it is a suitable indicator for pressures related to urbanization, although a confounding effect of wave exposure is possible. Invertebrate abundance responded strongly to eutrophication, but the indicator based on taxonomic composition (Average Score Per Taxon) did not. Our results suggest that our metrics can be applied in Western Balkan lakes, despite the high number of endemic species present in some of these lakes. We argue that local water management should focus on abating the causes of eutrophication and water level fluctuation, whilst preserving sufficient lengths of undeveloped shoreline to ensure good water quality in the long run.

Wild cereal grain consumption among Early Holocene foragers of the Balkans predates the arrival of agriculture.

Forager focus on wild cereal plants has been documented in the core zone of domestication in southwestern Asia, while evidence for forager use of wild grass grains remains sporadic elsewhere. In this paper, we present starch grain and phytolith analyses of dental calculus from 60 Mesolithic and Early Neolithic individuals from five sites in the Danube Gorges of the central Balkans. This zone was inhabited by likely complex Holocene foragers for several millennia before the appearance of the first farmers ~6200 cal BC. We also analyzed forager ground stone tools (GSTs) for evidence of plant processing. Our results based on the study of dental calculus show that certain species of Poaceae (species of the genus Aegilops) were used since the Early Mesolithic, while GSTs exhibit traces of a developed grass grain processing technology. The adoption of domesticated plants in this region after ~6500 cal BC might have been eased by the existing familiarity with wild cereals.

Before humans invented agriculture and the first farmers appeared in southwestern Asia, other ancient foragers (also known as hunter-gatherers) in southeastern Europe had already developed a taste for consuming wild plants. There is evidence to suggest that these foragers were intensely gathering wild cereal grains before the arrival of agriculture. However, until now, the only place outside southwestern Asia this has been shown to have occurred is in Greece, and is dated around 20,000 years ago. In the past, researchers proposed that forager societies in the Balkans also consumed wild cereals before transitioning to agriculture. But this has been difficult to prove because plant foods are less likely to preserve than animal bones and teeth, making them harder to detect in prehistoric contexts. To overcome this, Cristiani et al. studied teeth from 60 individuals found in archaeological sites between Serbia and Romania, which are attributed to the Mesolithic and Early Neolithic periods. Food particles extracted from crusty deposits on the teeth (called the dental calculus) were found to contain structures typically found in plants. In addition, Cristiani et al. discovered similar plant food residues on ground stone tools which also contained traces of wear associated with the processing of wild cereals. These findings suggest that foragers in the central Balkans were already consuming certain species of wild cereal grains 11,500 years ago, before agriculture arrived in Europe. It is possible that sharing knowledge about plant resources may have helped introduce domesticated plant species in to this region as early as 6500 BC. This work challenges the deep-rooted idea that the diet of hunter-gatherers during the Palaeolithic and Mesolithic periods primarily consisted of animal proteins. In addition, it highlights the active role the eating habits of foragers might have played in introducing certain domesticated plant species that have become primary staples of our diet today.

Tracking the transition to agriculture in Southern Europe through ancient DNA analysis of dental calculus.

Archaeological dental calculus, or mineralized plaque, is a key tool to track the evolution of oral microbiota across time in response to processes that impacted our culture and biology, such as the rise of farming during the Neolithic. However, the extent to which the human oral flora changed from prehistory until present has remained elusive due to the scarcity of data on the microbiomes of prehistoric humans. Here, we present our reconstruction of oral microbiomes via shotgun metagenomics of dental calculus in 44 ancient foragers and farmers from two regions playing a pivotal role in the spread of farming across Europe-the Balkans and the Italian Peninsula. We show that the introduction of farming in Southern Europe did not alter significantly the oral microbiomes of local forager groups, and it was in particular associated with a higher abundance of the species Olsenella sp. oral taxon 807. The human oral environment in prehistory was dominated by a microbial species, Anaerolineaceae bacterium oral taxon 439, that diversified geographically. A Near Eastern lineage of this bacterial commensal dispersed with Neolithic farmers and replaced the variant present in the local foragers. Our findings also illustrate that major taxonomic shifts in human oral microbiome composition occurred after the Neolithic and that the functional profile of modern humans evolved in recent times to develop peculiar mechanisms of antibiotic resistance that were previously absent.

Dispersals as demographic processes: testing and describing the spread of the Neolithic in the Balkans.

Although population history and dispersal are back at the forefront of the archaeological agenda, they are often studied in relative isolation. This contribution aims at combining both dimensions, as population dispersal is, by definition, a demographic process. Using a case study drawn from the Early Neolithic of South-Eastern Europe, we use radiocarbon dates to jointly investigate changes in speed and population size linked to the new food production economy and demonstrate that the spread of farming in this region corresponds to a density-dependent dispersal process. The implications of this characterization are evaluated in the discussion. This article is part of the theme issue 'Cross-disciplinary approaches to prehistoric demography'.

Release of wood extractable elements in experimental spirit model: Health risk assessment of the wood species generated in Balkan cooperage.

This work investigates the release of toxic elements from wood into the experimental spirit models and the safety risks for consumers. The spirit models were prepared as ethanolic extracts using the procedure which reproduces maturation of spirits. Investigation included staves of wood species commonly used in Balkan cooperage: mulberry, Myrobalan plum, black locust, wild cherry, and various oaks. Potassium was the most abundant element, except in the wild cherry extract where calcium was dominant, and the Myrobalan plum extract where phosphorus was the most abundant. The parameters for the health risk assessment, such as hazard index (HI) and hazard quotient (HQ) were calculated for potentially toxic elements and indicated that all wood extracts would be safe for human consumption. Owing to the proven abundance of phenolics in the investigated wood extracts, relations among elements and phenolics were also studied and conclusions were made based on the statistically significant correlations.

Littoral eutrophication indicators are more closely related to nearshore land use than to water nutrient concentrations: A critical evaluation of stressor-response relationships.

Biological assessment metrics and water chemistry measurements are used to quantify the link between stressors and their effects on lake ecosystems, for the Water Framework Directive. However, correlations between metrics and water chemistry are often poor. This is seen as major weaknesses of Water Framework Directive-related monitoring and assessment. We analyzed macrophytes, benthic algae, benthic macroinvertebrates, water chemistry and sediment total phosphorus content in the littoral of six lakes in the Western Balkans and used CORINE land use data to estimate nutrient enrichment via runoff from the adjacent land. Lakes with a higher estimated phosphorus runoff from the adjacent land did not have higher littoral water nutrient concentrations, but littoral diatom assemblages indicated more eutrophic conditions. These lakes also had higher abundances of littoral benthic primary producers, which in turn were associated with low concentrations of dissolved nutrients, but only in autumn, not in spring. This is consistent with primary producers taking up nutrients during the summer growth season. In lakes with high abundances of benthic primary producers, it is likely that the littoral vegetation plays a large role in the transfer of nutrients from the water to the benthos. This process impairs correlations between biological metrics and water nutrient concentrations. Our results suggest that CORINE land cover may be more useful to characterize littoral nutrient enrichment than lake water chemistry. Increased benthic primary producer biomasses and "eutrophic" diatom indices may indicate littoral nutrient enrichment even if water nutrient concentrations are low.

Genetic diversity, reproductive capacity and alkaloids content in three endemic Alkanna species.

The Balkans endemic species Alkanna primuliflora Griseb., A. stribrnyi Velen., and A. graeca Boiss. & Spruner have limited distribution in the Balkan Peninsula and a large variation in the morphological characteristics. The populations of the three Alkanna species in the Bulgarian flora are small and fragmented. There are no previous reports on the chemical profile or on the embryology of these species. The hypothesis was that the limited distribution of A. primuliflora, A. stribrnyi, and A. graeca was due to their reproductive capacity and genetic diversity. Furthermore, we hypothesized that the three species will contain pyrrolizidine alkaloids (PAs), as other species of the genus Alkanna (Boraginaceae), but they would have differential alkaloids composition. The population genetic structure and differentiation showed a clear distinction between species and revealed average levels of genetic diversity among the natural populations of the three Alkanna species. The embryological investigation observed stability of the processes in the male and female generative spheres and high viability of mature pollen and embryo of the three species. The normal formation of male and female gametophytes without deviations or degenerative processes, and observed levels of genetic diversity between Alkanna individuals are important in maintaining the size and resilience of the Alkanna populations. Eight alkaloids were identified by GC-MS in A. primuliflora and A. graeca and six alkaloids in A. stribrnyi. The main pyrrolizidine alkaloids (PAs) in all investigated species was triangularine. A. primuliflora and A. graeca showed similar chemical composition that comprised 9-angeloylretronecine, 7-tigloylretronecine, 9-tigloylretronecine, triangularicine, dihydroxytriangularine, dihydroxytriangularicine, whereas, in A. stribrnyi 9-tigloylretronecine, triangularicine and dihydroxytriangularicine were not found. This is the first report on the presence of PAs in A. primuliflora, A. stribrnyi and A. graeca. Besides, this is the first report on the embryology of these endemic species. The results contribute to the knowledge of the three endemic Alkanna species and will facilitate policy-making and defining new strategies for their conservation.

Balkans' Asteraceae Species as a Source of Biologically Active Compounds for the Pharmaceutical and Food Industry.

Herbal drugs are a useful source of different bioactive compounds. Asteraceae species, as the most widespread vascular plants, can be used both as food and as medicine due to the great diversity of recorded chemical components - different phenolic compounds, terpenes, carotenoids, vitamins, alkaloids, etc. The Balkan Peninsula is characterized by great diversity of plants from Asteraceae family, including presence of rare and endemic species. In this review, results of the survey of chemical composition and biological activity, mainly focusing on antioxidant, antimicrobial and anticancer effects of selected Balkans' Asteraceae species were provided. In addition, information on edible plants from Asteraceae family is presented, due to growing interest for the so-called 'healthy diet' and possible application of Balkans' Asteraceae species as food of high nutritional value or as a source of functional food ingredients.

Phytochemical Study of Eight Medicinal Plants of the Lamiaceae Family Traditionally Used as Tea in the Sharri Mountains Region of the Balkans.

In the present study, eight plant species belonging to Lamiaceae family were identified as ingredients for herbal teas in the region of Sharri Mountains: Thymus serpyllum, Rosmarinus officinalis, Melissa officinalis, Origanum vulgare, Mentha longifolia, Ocimum basilicum, Teucrium chamaedrys, and Sideritis scardica, respectively. Chemical composition of essential oils obtained from these species was analyzed using GC-MS and GC-FID with the aim of examining their volatile compound profiles, responsible for their respective flavors and fragrance. Principal Component Analysis (PCA) was performed with the aim of grouping plant species under study on the basis of their chemical composition. Experimental data revealed the typical volatile constituent pattern for the Lamiaceae family. Monoterpenes and sesquiterpenes, responsible for flavor and medicinal use of these plants, were the most abundant groups of the volatile constituents. PCA data analysis resulted in the grouping of these analyzed species in four principal clusters.

Is food more than a means of survival? An overview of the Balkan prison systems.

Food is a versatile national, social, and cultural marker. It represents more than just a means of survival (Stajcic, 2013); it is an expression of identity (Jones, 2017). Food has a symbolic power and carries a sense of community, relays customs, habits, and values. According to Godderis (2006), people "do" food. In institutional settings, such as prisons, often stripped of basic human rights and dignity, food can acquire yet another dimensions. It can become a means to pass time, regain normalcy, and cope with daily hardships. Despite its multifaceted importance, there is a paucity of research on prisoners' diet, with most being done on the US, UK, and Scandinavian prison systems (Smoyer, 2019; Smoyer & Kjaer Minke, 2015). This article drew from academic and non-academic sources (e.g., government reports, newspaper articles, prison blogs) to provide an overview of the Balkan prison systems through the lens of food. It will present weekly menus from three different countries and discuss alternative ways of accessing food in prisons (i.e., through prison commissary, prison farms, and food packages). It will further demonstrate prisoners' use of food to regain autonomy in the context of multiple deprivations. Lastly, this paper will reflect on the role of food, coffee, and cigarettes in prisoners' socialization, as well as in reiteration of prisoner subculture.

Concomitant occurrence of anthropogenic air pollutants, mineral dust and fungal spores during long-distance transport of ragweed pollen.

Large-scale synoptic conditions are able to transport considerable amounts of airborne particles over entire continents by creating substantial air mass movement. This phenomenon is observed in Europe in relation to highly allergenic ragweed (Ambrosia L.) pollen grains that are transported from populations in Central Europe (mainly the Pannonian Plain and Balkans) to the North. The path taken by atmospheric ragweed pollen often passes through the highly industrialised mining region of Silesia in Southern Poland, considered to be one of the most polluted areas in the EU. It is hypothesized that chemical air pollutants released over Silesia could become mixed with biological material and be transported to less polluted regions further North. We analysed levels of air pollution during episodes of long-distance transport (LDT) of ragweed pollen to Poland. Results show that, concomitantly with pollen, the concentration of air pollutants with potential health-risk, i.e. SO2, and PM10, have also significantly increased (by 104% and 37%, respectively) in the receptor area (Western Poland). Chemical transport modelling (EMEP) and air mass back-trajectory analysis (HYSPLIT) showed that potential sources of PM10 include Silesia, as well as mineral dust from the Ukrainian steppe and the Sahara Desert. In addition, atmospheric concentrations of other allergenic biological particles, i.e. Alternaria Nees ex Fr. spores, also increased markedly (by 115%) during LDT episodes. We suggest that the LDT episodes of ragweed pollen over Europe are not a "one-component" phenomenon, but are often related to elevated levels of chemical air pollutants and other biotic and abiotic components (fungal spores and desert dust).

Maternal age has more pronounced effect on breast milk retinol and ß-carotene content than maternal dietary pattern.

OBJECTIVE: The effects on breast milk composition of advanced maternal age and maternal dietary habits during pregnancy and lactation have not, to our knowledge, been investigated in southeastern Europe and the Balkans. The aim of this study was to compare the content of retinol and ß-carotene in colostrum and mature milk samples obtained from different maternal age (MA) groups and to assess the potential relationship with maternal and demographic characteristics, dietary patterns, and lifestyle habits during pregnancy and lactation. METHODS: Forty-three nursing mothers were divided in two groups according to MA: ≥35 y of age (n = 22) and <35 y of age (n = 21). Total lipid concentrations were determined by gravimetric method, whereas retinol and ß-carotene contents were assessed by high-performance liquid chromatography method. Dietary patterns during pregnancy and lactation were assessed using food frequency questionnaires, and principal component analysis (PCA) statistical analysis was performed. RESULTS: Except for retinol levels in mature milk, significantly higher levels of total fats, retinol, and ß-carotene were found in the older group. Results of PCA analysis showed that MA was strongly correlated with fat content, retinol, and ß-carotene levels in colostrum samples, whereas in mature milk samples MA was highly correlated with fat content and moderately with ß-carotene. In terms of dietary patterns, retinol contents in milk samples from both groups were weakly to moderately correlated with consumption frequency of eggs, meat, milk and dairy products, whereas ß-carotene contents were weakly to strongly associated with consumption frequency of fruits and vegetables. CONCLUSIONS: PCA analysis used in the study clearly confirmed that MA, total lipids, retinol, and ß-carotene levels might serve as a good criterion for delimitation of breast milk samples collected in different stages of lactation from mothers of various ages. The present findings could represent key basis for further investigations.

Essential oil composition of the Balkan endemic Thymus longedentatus (Degen & Urum. ) Ronniger / Composición del aceite esencial de Thymus longedentatus (Degen & Urum. ) Ronniger endemic de los Balcanes

The chemical composition of essential oil obtained from the aerial parts of the Balkan endemic species Thymus longedentatus was studied by GC-MS. Twenty eight compounds, consisting 98.2% of the total components were detected in amounts exceeding 0.1%. The oil was characterized by relatively high concencentration of oxygentated monoterpenes (78.7%), among which citral isomers neral (27.5%) and geranial (30.3%) were the principal ones. In addition, 1,8-cineole (7.8%), trans-ß-ocimene (7.5%), and ß-myrcene (3.7%) were detected in significant ammounts. Germacrene D (4.4%) was found to be the main sesquiterpene in the essential oil.

Se estudió mediante GC-MS la composición química del aceite esencial obtenido de las partes aéreas de Thymus longedentatus, especie endémica de los Balcanes. Se detectaron veintiocho compuestos, que representaban un 98,2% del total de compuestos y que se encontraban en cantidades superiores al 0,1%. El aceite se caracterizó por una concentración relativamente alta de monoterpenos oxigenados (78.7%), entre los cuales los isómeros de citral, neral (27.5%) y geranial (30.3%) eran los principales. Además, se detectó 1,8-cineol (7,8%), trans-ß-ocimeno (7,5%) y ß-mirceno (3,7%) en cantidades significativas. Se encontró que Germacreno D (4.4%) es el principal sesquiterpeno en el aceite esencial.

Bioactivity-Guided Isolation of Anti-Inflammatory Constituents of the Rare Mushroom Calvatia nipponica in LPS-Stimulated RAW264.7 Macrophages.

Calvatia species, generally known as puffball mushrooms, are used both as sources of food and as traditional medicine. Among the Calvatia genus, Calvatia nipponica (Agaricaceae) is one of the rarest species. Using bioassay-guided fractionation based on anti-inflammatory effects, five alkaloids (1 - 5), two phenolics (6 and 7), and a fatty acid methyl ester (8) were isolated from the fruiting bodies of C. nipponica. Compound 8 was identified from C. nipponica for the first time, and all isolates (1 - 8) were tested for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compound 7 showed mild inhibition while compound 8 significantly inhibited NO production with an IC50 value of 27.50 ± 0.08 µm. The mechanism of NO inhibition of compound 7 was simulated by molecular docking analysis against nitric oxide synthase (iNOS), which revealed the interactions of 7 with the key amino acid residue and the heme in the active site. With the most potent inhibition against LPS-induced inflammation, compound 8 was further investigated with respect to its mechanism of action, and the activity was found to be mediated through the inhibition of iNOS and COX-2 expression.

Exceptionally high levels of lead pollution in the Balkans from the Early Bronze Age to the Industrial Revolution.

The Balkans are considered the birthplace of mineral resource exploitation and metalworking in Europe. However, since knowledge of the timing and extent of metallurgy in southeastern Europe is largely constrained by discontinuous archaeological findings, the long-term environmental impact of past mineral resource exploitation is not fully understood. Here, we present a high-resolution and continuous geochemical record from a peat bog in western Serbia, providing a clear indication of the extent and magnitude of environmental pollution in this region, and a context in which to place archaeological findings. We observe initial evidence of anthropogenic lead (Pb) pollution during the earliest part of the Bronze Age [∼3,600 years before Common Era (BCE)], the earliest such evidence documented in European environmental records. A steady, almost linear increase in Pb concentration after 600 BCE, until ∼1,600 CE is observed, documenting the development in both sophistication and extent of southeastern European metallurgical activity throughout Antiquity and the medieval period. This provides an alternative view on the history of mineral exploitation in Europe, with metal-related pollution not ceasing at the fall of the western Roman Empire, as was the case in western Europe. Further comparison with other Pb pollution records indicates the amount of Pb deposited in the Balkans during the medieval period was, if not greater, at least similar to records located close to western European mining regions, suggestive of the key role the Balkans have played in mineral resource exploitation in Europe over the last 5,600 years.