Gabriela Kehayova

Dr. Gabriela Kehayova

orcid

Research Focus & Metrics

Academic Career Length

9Years (2018-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

View All Publications
12 October 2024 in NeuroSci
Verified
Journal Article
Open access
PDF file
BSBorislav Sevriev
Borislav Sevriev
SDSimeonka Dimitrova Dimitrova
Simeonka Dimitrova Dimitrova
GKGabriela Kehayova
Gabriela Kehayova
Stela DragomanovaStela Dragomanova
Stela Dragomanova
Trehalose is a naturally occurring disaccharide that has recently gained significant attention for its neuroprotective properties in various models of neurodegeneration. This review provides an overview of available experimental data on the beneficial properties of trehalose for central nervous system pathological conditions. Trehalose’s impact on neuronal cell survival and function was also examined. As a result, we identified that trehalose’s neuroprotection includes autophagy modulation as well as its capability to stabilize proteins and inhibit the formation of misfolded ones. Moreover, trehalose mitigates oxidative stress-induced neuronal damage by stabilizing cellular membranes and modulating mitochondrial function. Furthermore, trehalose attenuates excitotoxicity-induced neuroinflammation by suppressing pro-inflammatory cytokine release and inhibiting inflammasome activation. A possible connection of trehalose with the gut–brain axis was also examined. These findings highlight the potential therapeutic effects of trehalose in neurodegenerative diseases. According to the conclusions drawn from this study, trehalose is a promising neuroprotective agent as a result of its distinct mechanism of action, which makes this compound a candidate for further research and the development of therapeutic strategies to combat neuronal damage and promote neuroprotection in various neurological diseases.

Verified
Journal Article
Open access
PDF file
DCDesislava Ivanova Cherneva
Desislava Ivanova Cherneva
GKGabriela Kehayova
Gabriela Kehayova
SDSimeonka Dimitrova Dimitrova
Simeonka Dimitrova Dimitrova
Stela DragomanovaStela Dragomanova
Stela Dragomanova
N-acetylcysteine (NAC) has garnered increasing interest for its neurotherapeutic capabilities beyond its recognized functions as a mucolytic agent and an antidote for acetaminophen toxicity. This review consolidates findings from both preclinical and clinical studies to investigate NAC’s diverse modulatory effects on the central nervous system (CNS). NAC primarily functions as an antioxidant by replenishing glutathione and mitigating oxidative stress; however, it produces glutathione-independent effects through the modulation of mitochondrial redox systems, ferroptosis, and the Nrf2-ARE signaling pathway. It plays a significant role in neuroinflammatory processes by inhibiting the production of cytokines, the expression of iNOS, and the activation of microglia. Furthermore, NAC affects various neurotransmitter systems—including glutamatergic, dopaminergic, GABAergic, serotonergic, cholinergic, and adrenergic pathways—by modulating synaptic transmission, receptor activity, and transporter functionality. It promotes neuroprotection through the enhancement of neurotrophic factors, the preservation of mitochondrial integrity, and the upregulation of survival signaling pathways. Recent evidence also emphasizes NAC’s role in gene expression and the regulation of cortisol levels. The extensive range of NAC’s neurobiological effects highlights its therapeutic potential in treating neurodegenerative and neuropsychiatric disorders. Nevertheless, the variability in clinical outcomes indicates a pressing need for more focused, mechanism-based research.

Verified
Journal Article
Open access
PDF file
Daniela DimitrovaDaniela Dimitrova
Daniela Dimitrova
SDSimeonka Dimitrova Dimitrova
Simeonka Dimitrova Dimitrova
GKGabriela Kehayova
Gabriela Kehayova
Stela DragomanovaStela Dragomanova
Stela Dragomanova
Background: Meroterpenoids represent a remarkably diverse class of natural secondary metabolites, some of which are synthesized via terpenoid biosynthetic pathways. Over the past ten years, these compounds have gained interest because of their wide range of biological activities, such as anti-cholinesterase, COX-2 inhibitory, antibacterial, antiviral, antidiabetic, antioxidant, anti-inflammatory, antineoplastic, and cardioprotective properties. This review aims to consolidate the recognized neuroprotective effects of meroterpenoids from marine and terrestrial fungi. Methods: Data compiled from several databases, including PubMed, Science Direct, Scopus, and Google Scholar, include articles published since 2000 using keywords such as “neuroprotective”, “fungi”, “mushroom”, “marine sponge”, “neurodegeneration”, and “dementia” in connection with “meroterpenoids”. Results: Meroterpenoids modulate different cell signaling pathways and exhibit different and often combined mechanisms of action to ameliorate neuronal damage and dysfunction. Reported activities include anti-cholinesterase, antioxidant, BACE1 inhibition, and anti-inflammatory activities, all of which have potential in the treatment of dementia associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Conclusions: Meroterpenoids have the potential to be developed as effective tools for neuropathological diseases. Ongoing research to elucidate the various neuroprotective pathways remains essential and requires further investigation.

15 November 2025 in Marine Drugs
Verified
Journal Article
Open access
PDF file
Daniela DimitrovaDaniela Dimitrova
Daniela Dimitrova
GKGabriela Kehayova
Gabriela Kehayova
SDSimeonka Dimitrova Dimitrova
Simeonka Dimitrova Dimitrova
Stela DragomanovaStela Dragomanova
Stela Dragomanova
Alzheimer’s disease continues to be one of the most urgent neurodegenerative conditions, with acetylcholinesterase (AChE) inhibitors serving as a fundamental component of contemporary treatment approaches. Growing evidence underscores that marine ecosystems are a rich source of structurally varied and biologically active natural products exhibiting anticholinesterase properties. This review presents a thorough synthesis of marine-derived metabolites—including those sourced from bacteria, fungi, sponges, algae, and other marine life—that demonstrate inhibitory effects against AChE and butyrylcholinesterase (BuChE). Numerous compounds, such as meroterpenoids, alkaloids, peptides, and phlorotannins, not only show nanomolar to micromolar inhibitory activity but also reveal additional neuroprotective characteristics, including antioxidant effects, anti-amyloid properties, and modulation of neuronal survival pathways. Despite these encouraging findings, the transition to clinical applications is hindered by a lack of comprehensive pharmacokinetic, toxicity, and long-term efficacy studies. The structural variety of marine metabolites provides valuable frameworks for the development of next-generation cholinesterase inhibitors. Further interdisciplinary research is essential to enhance their therapeutic potential and facilitate their incorporation into strategies for addressing Alzheimer’s disease and related conditions.

4 July 2024 in Scientia Pharmaceutica
Verified
Journal Article
Open access
PDF file
SDSimeonka Dimitrova Dimitrova
Simeonka Dimitrova Dimitrova
Stela DragomanovaStela Dragomanova
Stela Dragomanova
GKGabriela Kehayova
Gabriela Kehayova
In recent years, an innovative approach has emerged in the field of toxicology for managing acute intoxications caused by lipophilic substances: intravenous lipid emulsions (ILEs). Through numerous experiments and case reports, the efficacy of lipid emulsions in counteracting toxicities induced by lipophilic agents, including a significant number of antiepileptic (AE) drugs, have become increasingly evident. Data spanning a 10-year period (2010–2020) were analyzed by searching through multiple scientific publication platforms like PubMed, Science Direct, Research Gate, and Springer Link. This study focused on reviewing relevant case reports detailing successful intravenous lipid emulsion (ILE) administration in patients with acute intoxications with antiepileptics, specifically examining the impact of fat emulsions on neurological status, Glasgow Coma Scale (GCS) scores, and corrected QT interval concerning hemodynamic instability. The typical symptoms of antiepileptic toxicity include central nervous system depression, ataxia, and nystagmus. Intravenous lipid emulsion application resulted in an increase in Glasgow Coma Scale scores and enhanced recovery from drug intoxication. This study provides a comprehensive overview of the potential utility of ILE as a component to antidote therapy in cases of acute AE poisoning involving neurotropic drugs. The process involves the engagement of various mechanisms of antitoxic activity.

12 April 2025 in Toxins
Verified
Journal Article
Open access
PDF file
Stanila Seryozheva Stoeva-GrigorovaStanila Seryozheva Stoeva-Grigorova
Stanila Seryozheva Stoeva-Grigorova
MRMaya Radeva-Ilieva
Maya Radeva-Ilieva
Stela DragomanovaStela Dragomanova
Stela Dragomanova
GKGabriela Kehayova
Gabriela Kehayova
SDSimeonka Dimitrova Dimitrova
Simeonka Dimitrova Dimitrova
SZSnezha Zlateva
Snezha Zlateva
The nature and epidemiology of plant intoxications are still not well understood, with recent data being limited. The present study aims to report cases of plant poisoning in the clinical practice of the Clinical Toxicology Department at the Naval Hospital—Varna, Bulgaria, over a 20-year period (2003–2023). A documentary retrospective analysis of the hospitalized cases of poisoning with poisonous plants and their grouping into toxidromes was performed. During the study period, patients with plant poisoning admitted to our hospital unit accounted for 0.35% of a total of 12,857 hospitalized individuals. The distribution across the toxidromes based on clinical presentation revealed the highest frequency of anticholinergic, cyanogen, and ricin toxidromes. The majority of the intoxications resulted from unintentional exposure to plant toxins in adult individuals. Most cases followed a mild to severe clinical course, with patient discharge occurring between 2 and 5 days. No fatalities were recorded, thanks to the reported treatment methods. A relatively low incidence of plant-related poisonings was observed, with their predominant manifestations affecting the gastrointestinal, nervous, and cardiovascular systems. Increased reporting of epidemiological data and clinical experiences in the management of plant intoxications would substantially enhance researchers’ understanding of them and facilitate the development of a standardized treatment protocol.