Extraction Temperatures Shape Water-Soluble Metabolite Profiles of Nepeta nuda L. and thus Modulate the Bioactive Properties Desislava Mantovska, Alexandra Kapogianni, Ginka Cholakova, Ivanka Tsacheva, Anton Hinkov, et al. Metabolites, 2026 Background: Plants of the genus Nepeta are widely used in ethnomedicine for treating inflammatory disorders due to their rich content of bioactive compounds. This study investigated how extraction temperature specifically affects the bioactive potential of aqueous extracts from wild-grown Nepeta nuda L. Methods: The previously used maceration approach for this plant was applied at 30–60 °C to flowers, leaves, and stems. Phytochemical profiling included spectrophotometric assays, metabolite identification, and quantification. Biological activities reported for this plant were assessed, including antioxidant, anti-inflammatory, antiviral, antiproliferative, and antibacterial capacities. Results: Extraction yield was highest in flowers and leaves, where it increased significantly with rising temperature, while stems were less productive. All plant organs exhibited notable bioactivity falling into two groups: lower temperatures (30 and 40 °C) were optimal for antiviral and anti-inflammatory effects, whereas and higher temperatures (50 and 60 °C) enhanced antioxidant potential. The phytochemical composition, evaluated at representative extraction temperatures, revealed differential accumulation of p-coumaric acid and luteolin in all organs at 40 °C, while extraction at 60 °C corresponded to elevated levels of phenolic compounds. Flower extracts were confirmed to have the richest metabolic composition and were therefore subjected to further investigation. Extracts obtained at 40 °C influenced C1q binding, supporting their anti-inflammatory activity, whereas extraction at 60 °C resulted in stronger antiproliferative activity in colon cancer cell line. Antibacterial effects were similar at both temperatures. Conclusions: These findings highlight the importance of optimizing extraction conditions for future pharmacological applications of N. nuda.
In Vivo Assessment of Anti-Inflammatory Effects of Aqueous Extracts of Nepeta nuda ssp. nuda L. in Experimental Model of Peripheral Inflammation in Male Long Evans Rats Milena Keremidarska-Markova, Veneta Evtimova-Koeva, Tsvetozar Penchev, Dilyana Doncheva-Stoimenova, Miroslava Zhiponova, et al. Life, 2025 Background: Recently various plants have attracted considerable scientific interest as potential therapeutic alternatives to known drugs used in anti-inflammatory therapy. Therefore, we have investigated the possible anti-inflammatory and analgesic effects of aqueous extracts from flowers of the medical plant Nepeta nuda ssp. nuda L. (naked catmint) in a model of acute peripheral inflammation induced by intraplantar injection of λ-carrageenan in the hind paw of Long Evans rats. Methods: Two routes of N. nuda extract application were used: locally by intraplantar injections at dosages of 2.5 mg/kg and 25 mg/kg and systemically by intraperitoneal administration at dosages of 50 mg/kg and 200 mg/kg, respectively. Paw volume was measured prior to the carrageenan application and 1, 2, 3, and 4 h after carrageenan injection. Spontaneous locomotor activity of the rats was assessed 3 h after carrageenan injection, corresponding to the peak of acute paw inflammation. Results: Local application of the higher N. nuda dose led to a marked reduction in inflammatory paw edema at the 4th hour after carrageenan injection, comparable to the effect of the positive control diclofenac sodium. Interestingly, a similar anti-inflammatory effect was observed at the 1st hour when both extract doses were administered intraperitoneally. Only the higher intraplantar dose of N. nuda extract significantly enhanced the vertical activity in comparison to the group treated with carrageenan alone. Conclusions: Our data indicate that the aqueous N. nuda extract possesses potent anti-inflammatory effects following both local and systemic administration in rats. Furthermore, when administered locally the extract exerts significant analgesic activity in inflammatory pain.
Blue–Red LED Light Modulates Morphophysiological and Metabolic Responses in the Medicinal Plant Nepeta nuda Miroslava Zhiponova, Grigor Zehirov, Krasimir Rusanov, Mila Rusanova, Miroslava Stefanova, et al. Plants, 2025 Light quality and duration profoundly influence the growth and productivity of plant species. This study investigated the effects of a blue–red LED light combination, known to induce flowering, on the physiological state and content of biologically active substances in catmint (Nepeta nuda L.) grown under controlled in vitro conditions. White light (W) was used as a control and compared with two blue–red intensities: BR (high-intensity blue–red light) and BRS (low-intensity blue–red light or “BR with shadow”). BR-treated plants showed increased leaf area, mesophyll thickness, biomass and starch content but reduced levels of plastid pigments. BR also modified the oxidative state of plants by inducing lipid peroxidation while simultaneously activating ROS scavenging mechanisms and enhancing phenolic antioxidants. Interestingly, BR decreased the accumulation of the Nepeta sp.-specific iridoid, nepetalactone. These effects appear to be regulated by the phytohormones auxin, abscisic acid and jasmonates. BRS treatment produced effects similar to the W control but led to increased plant height and reduced leaf area and thickness. Both BR and BRS regimes induced the accumulation of proteins and amino acids. We conclude that blue–red light can enhance the survival capacity of micropropagated N. nuda during subsequent soil adaptation, suggesting that similar light pre-treatment could improve plant performance under stress conditions.
Chemotaxonomy and Bioactive Potential of High-Mountain Plantago atrata Miroslava Zhiponova, Zhenya Yordanova, Georgi Ivanov, Uroš Gašić, Danijela Mišić, et al. Chemistry and Biodiversity, 2025 Plantago atrata Hoppe is a high‐altitude mountain plant exposed to harsh environmental factors. This study aims to elucidate the ecological, phytochemical and pharmacological characteristics of this lesser‐known plantain. Despite nutrient‐poor peat soil, the leaves of P. atrata contained increased levels of phosphorus, potassium and calcium, and the anatomy revealed an isobilateral mesophyll. Molecular taxonomic identification and phylogenetic analyses confirmed the classification of the studied plant as P. atrata and its clustering with narrow‐leaved plantains growing in extreme conditions. Detailed phytochemical profiles revealed primary and secondary metabolites that can be used as taxonomic identifiers and for bioactivity studies. The methanol fraction enriched in phenolic compounds appeared biologically active—by displaying limited antimicrobial activity, however, it possessed significant radical‐scavenging and anti‐inflammatory capacity. The data demonstrate that P. atrata’s leaf parameters and phytochemical arsenal assure plant survival and reveal the plantain's pharmaceutical potential in inhibiting inflammation via the classical pathway of Complement activation.
Functional Genomics of Legumes in Bulgaria—Advances and Future Perspectives Miglena Revalska, Mariana Radkova, Miroslava Zhiponova, Valya Vassileva, Anelia Iantcheva Genes, 2025 Members of the Leguminosae family are important crops that provide food, animal feed and vegetable oils. Legumes make a substantial contribution to sustainable agriculture and the nitrogen cycle through their unique ability to fix atmospheric nitrogen in agricultural ecosystems. Over the past three decades, Medicago truncatula and Lotus japonicus have emerged as model plants for genomic and physiological research in legumes. The advancement of innovative molecular and genetic tools, particularly insertional mutagenesis using the retrotransposon Tnt1, has facilitated the development of extensive mutant collections and enabled precise gene tagging in plants for the identification of key symbiotic and developmental genes. Building on these resources, twelve years ago, our research team initiated the establishment of a platform for functional genomic studies of legumes in Bulgaria. In the framework of this initiative, we conducted systematic sequencing of selected mutant lines and identified genes involved in plant growth and development for detailed functional characterization. This review summarizes our findings on the functions of selected genes involved in the growth and development of the model species, discusses the molecular mechanisms underlying important developmental processes and examines the potential for the translation of this fundamental knowledge to improve commercially important legume crops in Bulgaria and globally.
Biochemical acclimation of European beech (Fagus sylvatica L.) saplings to canopy opening Forestry Ideas, 2025
MICROALGAL OXIDATIVE STRESS RESPONSE TO Zn TOXICITY Oxidation Communications, 2025
Modulation of Zn Ion Toxicity in Pisum sativum L. by Phycoremediation Zornitsa Karcheva, Zhaneta Georgieva, Svetoslav Anev, Detelina Petrova, Momchil Paunov, et al. Plants, 2025 Microalgae offer a promising alternative for heavy metal removal, and the search for highly efficient strains is ongoing. This study investigated the potential of two microalgae, Coelastrella sp. BGV (Chlorophyta) and Arthronema africanum Schwabe & Simonsen (Cyanoprokaryota), to bind zinc ions (Zn2⁺) and protect higher plants. Hydroponically grown pea (Pisum sativum L.) seedlings were subjected to ZnSO4 treatment for 7 days in either a nutrient medium (Knop) or a microalgal suspension. The effects of increasing Zn2⁺ concentrations were evaluated through solution parameters, microalgal dry weight, pea growth (height, biomass), and physiological parameters, including leaf gas exchange, chlorophyll content, and normalized difference vegetation index (NDVI). Zinc accumulation in microalgal and plant biomass was also analyzed. The results revealed that microalgae increased pH and oxygen levels in the hydroponic medium while enhancing Zn accumulation in pea roots. At low ZnSO4 concentrations (2–5 mM), microalgal suspensions stimulated pea growth and photosynthetic performance. However, higher ZnSO4 levels (10–15 mM) caused Zn accumulation, leading to nutrient deficiencies and growth suppression in microalgae, which ultimately led to physiological disturbances in peas. Coelastrella sp. BGV exhibited greater tolerance to Zn stress and provided a stronger protective effect when co-cultivated with peas, highlighting its potential for phycoremediation applications.
EFFECT OF THE MULCHING APPROACH ON THE OXIDATIVE STRESS IN Solanum tuberosum Oxidation Communications, 2025
Pulsed Electric Field Pretreatment Enhances the Enzyme Hydrolysis of Baker’s Yeast Ralitsa Veleva, Valentina Ganeva, Miroslava Zhiponova Microorganisms, 2024 Baker’s yeast is a key starting material for producing extracts with diverse compositions and applications. This study investigates the effect of pulsed electric field (PEF) pretreatment, which induces irreversible electropermeabilization, on the enzymatic hydrolysis of yeast. Cell suspensions were exposed to monopolar rectangular pulses in a continuous flow system followed by 4 h of incubation with Alcalase at concentrations of 0.2% and 0.5%. PEF pretreatment significantly improved enzymatic hydrolysis, with maximum intracellular content recovery under electrical conditions resulting in outlet temperatures of 56–58 °C. The released protein reached 163.7 ± 13 mg per gram of dry cell weight (DCW). SDS-PAGE analysis showed that the extracts predominantly contained peptides with molecular masses below 4.7 kDa. The phenolic content was comparable to that of cell lysates obtained after mechanical disruption. The free α-amino nitrogen content and total antioxidant activity reached 218.2 ± 26 mg/gDCW and 53.4 ± 4.6 mg TE/gDCW, respectively, representing 3.2-fold and 2.65-fold increases compared to cell lysates. The hydrolysates from PEF-pretreated cells demonstrated a positive effect on the proliferation of the human keratinocyte cell line HaCat. The obtained data lead to the conclusion that PEF pretreatment is a promising approach to enhance the production of yeast hydrolysates with various applications.
Extraction Temperatures Shape Water-Soluble Metabolite Profiles of Nepeta nuda L. and thus Modulate the Bioactive Properties D Mantovska, A Kapogianni, G Cholakova, I Tsacheva, A Hinkov, ... Metabolites 16 (5), 323 , 2026 2026
Investigation on the effect of regenerative organic farming strategies on the productivity of Solanum tuberosum and Phaseolus vulgaris and soil substrate parameters D Danchev, V Manova, Z Stoyanova, G Bonchev, M Zhiponova ARPHA Conference Abstracts 9, e181730 , 2026 2026
In Vivo Assessment of Anti-Inflammatory Effects of Aqueous Extracts of Nepeta nuda ssp. nuda L. in Experimental Model of Peripheral Inflammation in Male Long … M Keremidarska-Markova, V Evtimova-Koeva, T Penchev, ... Life 15 (12), 1938 , 2025 2025 Citations: 2
Interdisciplinary biotechnological approach for analysis and modulation of the biological potential of the medicinal plant Nepeta nuda M Zhiponova ARPHA Conference Abstracts 8, e177507 , 2025 2025
Blue–Red LED Light Modulates Morphophysiological and Metabolic Responses in the Medicinal Plant Nepeta nuda M Zhiponova, G Zehirov, K Rusanov, M Rusanova, M Stefanova, ... Plants 14 (15), 2285 , 2025 2025 Citations: 2
EFFECT OF THE MULCHING APPROACH ON THE OXIDATIVE STRESS IN Solanum tuberosum. D DANCHEV, M PAUNOV, AM NEDELCHEVA, V VLADIMIROVA, ... Oxidation Communications 48 (3) , 2025 2025
Chemotaxonomy and Bioactive Potential of High‐Mountain Plantago atrata M Zhiponova, Z Yordanova, G Ivanov, U Gašić, D Mišić, K Alipieva, ... Chemistry & Biodiversity 22 (6), e202402433 , 2025 2025 Citations: 3
Functional genomics of legumes in Bulgaria—Advances and future perspectives M Revalska, M Radkova, M Zhiponova, V Vassileva, A Iantcheva Genes 16 (3), 296 , 2025 2025 Citations: 1
Modulation of Zn Ion Toxicity in Pisum sativum L. by Phycoremediation Z Karcheva, Z Georgieva, S Anev, D Petrova, M Paunov, M Zhiponova, ... Plants 14 (2), 215 , 2025 2025 Citations: 3
MICROALGAL OXIDATIVE STRESS RESPONSE TO Zn TOXICITY. Z KARCHEVA, ZH GEORGIEVA, D PETROVA, M ZHIPONOVA, ... Oxidation Communications 48 (1) , 2025 2025 Citations: 3
Plant-soil interactions and mulching affect the physico-chemical soil parameters and the physiological state of Solanum tuberosum L. and Phaseolus vulgaris L. D Danchev, M Paunov, S Anev, AM Nedelcheva, V Vladimirova, ... Ecologia Balkanica 16 (2) , 2024 2024
Pulsed Electric Field Pretreatment Enhances the Enzyme Hydrolysis of Baker’s Yeast R Veleva, V Ganeva, M Zhiponova Microorganisms 12 (12), 2470 , 2024 2024 Citations: 3
In Vitro Anticancer Effects of Aqueous Leaf Extract from Nepeta nuda L. ssp. nuda Z Gospodinova, G Antov, S Stoichev, M Zhiponova Life 14 (12), 1539 , 2024 2024 Citations: 9
Blue Light Enhances the Antioxidant, Antimicrobial, and Antitumor Potential of the Green Microalgae Coelastrella sp. BGV Z Georgieva, Z Karcheva, T Toshkova-Yotova, A Georgieva, R Toshkova, ... Plants 13 (23), 3295 , 2024 2024 Citations: 9
Cytokinins enhance the metabolic activity of in vitro-grown catmint (Nepeta nuda L.) M Zhiponova, Z Yordanova, A Zaharieva, L Ivanova, U Gašić, D Mišić, ... Plant Physiology and Biochemistry 214, 108884 , 2024 2024 Citations: 11
Taxonomic fingerprints of Plantago atrata Hoppe–a Review G Ivanov, A Kercheva, A Tosheva, Z Yordanova, M Zhiponova IOP Conference Series: Earth and Environmental Science 1305 (1), 012003 , 2024 2024 Citations: 2
The secrets of the edelweiss (Leontopodium R. Br. ex Cass.): a review on this symbol, scientific object, and natural treasure AA Pozumentshtikov, IA Boycheva, GN Bonchev, ML Kitanova, ... Годишник на Софийския Университет „Св. Климент Охридски “, Биологически … , 2024 2024 Citations: 2
Report on the career forum 2024: event planning, impact and reflections on past successes at the Faculty of Biology ZD Zheleva, YY Georgiev, MY Gendzhova, LS Novoselski, TP Koleva, ... Годишник на Софийския Университет „Св. Климент Охридски “, Биологически … , 2024 2024
Report on the seventh international “fascination of plants day”(FoPD) that brought to light the voluntary spirit into the Faculty of Biology YY Georgiev, ZD Zheleva, DI Mantovska, AMR Nedelcheva, AV Iantcheva, ... Годишник на Софийския Университет „Св. Климент Охридски “, Биологически … , 2024 2024
Biochemical acclimation of European beech (Fagus sylvatica L.) saplings to canopy opening S Anev, Z Karcheva, M Zhiponova, G Chaneva Forestry Ideas 31 (1), 22-36 , 2024 2024 Citations: 1
MOST CITED SCHOLAR PUBLICATIONS
Brassinosteroids control meristem size by promoting cell cycle progression in Arabidopsis roots MP González-García, J Vilarrasa-Blasi, M Zhiponova, F Divol, ... Development 138 (5), 849-859 , 2011 2011 Citations: 649
SPEECHLESS integrates brassinosteroid and stomata signalling pathways GE Gudesblat, J Schneider-Pizoń, C Betti, J Mayerhofer, I Vanhoutte, ... Nature cell biology 14 (5), 548-554 , 2012 2012 Citations: 378
Brassinosteroid production and signaling differentially control cell division and expansion in the leaf MK Zhiponova, I Vanhoutte, V Boudolf, C Betti, S Dhondt, F Coppens, ... New Phytologist 197 (2), 490-502 , 2013 2013 Citations: 230
POLAR-guided signalling complex assembly and localization drive asymmetric cell division A Houbaert, C Zhang, M Tiwari, K Wang, A de Marcos Serrano, ... Nature 563 (7732), 574-578 , 2018 2018 Citations: 203
Helix–loop–helix/basic helix–loop–helix transcription factor network represses cell elongation in Arabidopsis through an apparent incoherent feed-forward loop MK Zhiponova, K Morohashi, I Vanhoutte, K Machemer-Noonan, ... Proceedings of the National Academy of Sciences 111 (7), 2824-2829 , 2014 2014 Citations: 85
Osmotic stress responses of wheat species and cultivars differing in drought tolerance: some interesting genes (advices for gene hunting) L Erdei Acta Biologica Szegediensis 46 (3-4), 63-65 , 2002 2002 Citations: 71
Activation of an alfalfa cyclin‐dependent kinase inhibitor by calmodulin‐like domain protein kinase A Pettkó‐Szandtner, T Mészáros, GV Horváth, L Bakó, É Csordás‐Tóth, ... The Plant Journal 46 (1), 111-123 , 2006 2006 Citations: 61
Extraction of proteins and other intracellular bioactive compounds from baker’s yeasts by pulsed electric field treatment V Ganeva, B Angelova, B Galutzov, V Goltsev, M Zhiponova Frontiers in Bioengineering and Biotechnology 8, 552335 , 2020 2020 Citations: 57
Revealing the reviving secret of the white dead nettle ( Lamium album L.) ZP Yordanova, MK Zhiponova, ET Iakimova, MA Dimitrova, ... Phytochemistry reviews 13 (2), 375-389 , 2014 2014 Citations: 50
Brassinosteroids regulate the thylakoid membrane architecture and the photosystem II function S Krumova, M Zhiponova, K Dankov, V Velikova, K Balashev, T Andreeva, ... Journal of Photochemistry and Photobiology B: Biology 126, 97-104 , 2013 2013 Citations: 45
Tissue culture applications of Artemisia annua L. callus for indirect organogenesis and production phytochemical E Zayova, T Nedev, D Petrova, M Zhiponova, V Kapchina, G Chaneva Plant Tissue Culture and Biotechnology 30 (1), 97-106 , 2020 2020 Citations: 36
Adaptive changes in photosynthetic performance and secondary metabolites during white dead nettle micropropagation V Kapchina-Toteva, MA Dimitrova, M Stefanova, D Koleva, K Kostov, ... Journal of Plant Physiology 171 (15), 1344-1353 , 2014 2014 Citations: 35
Mitosis-Specific Promoter of the Alfalfa Cyclin-Dependent Kinase Gene ( Medsa;CDKB2;1 ) Is Activated by Wounding and Ethylene in a Non-Cell Division … MK Zhiponova, A Pettkó-Szandtner, E Stelkovics, Z Neer, S Bottka, ... Plant Physiology 140 (2), 693-703 , 2006 2006 Citations: 34
Catmint ( Nepeta nuda L.) Phylogenetics and Metabolic Responses in Variable Growth Conditions D Petrova, U Gašić, L Yocheva, A Hinkov, Z Yordanova, G Chaneva, ... Frontiers in Plant Science 13, 866777 , 2022 2022 Citations: 30
Effect of N 6 -benzyladenine and indole-3-butyric acid on photosynthetic apparatus of Orthosiphon stamineus plants grown in vitro D Stoyanova-Koleva, M Stefanova, M Zhiponova, V Kapchina-Toteva Biologia plantarum 56 (4), 607-612 , 2012 2012 Citations: 19
Uncovering the Interrelation between Metabolite Profiles and Bioactivity of In Vitro- and Wild-Grown Catmint ( Nepeta nuda L.) A Zaharieva, K Rusanov, M Rusanova, M Paunov, Z Yordanova, ... Metabolites 13 (10), 1099 , 2023 2023 Citations: 18
Comparative determination of the essential oil composition in Bulgarian endemic plant Achillea thracica Velen. during the process of ex situ conservation ZP Yordanova, MA Rogova, MK Zhiponova, MI Georgiev, ... Phytochemistry Letters 20, 456-461 , 2017 2017 Citations: 18
Establishment of embryogenic potential of economically important Bulgarian alfalfa cultivars (Medicago sativa L.) A Barbulova, A Iantcheva, M Zhiponova, M Vlahova, A Atanassov Biotechnology & Biotechnological Equipment 16 (1), 55-63 , 2002 2002 Citations: 18
Overexpression of the NMig1 Gene Encoding a NudC Domain Protein Enhances Root Growth and Abiotic Stress Tolerance in Arabidopsis thaliana V Velinov, I Vaseva, G Zehirov, M Zhiponova, M Georgieva, ... Frontiers in Plant Science 11, 815 , 2020 2020 Citations: 16
Efficient protocol for mass micropropagation of Artemisia annua L. GTC EG Zayova, TA Nedev, DH Petrova, MK Zhiponova GSC Biological and Pharmaceutical Sciences 5, 59-68 , 2018 2018 Citations: 16