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Redox-Active Molecules as Key Players for Inflammatory Diseases

A Special Issue of Molecules (ISSN 1420-3049) belonging to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 28 February 2027 | Viewed by 4807

Editor


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Guest Editor
Centre for Oxygen Research and Development (CO2RD), Center of Interdisciplinary Research on Medicines (CIRM), University of Liege, 4000 Liege, Belgium
Interests: chemical biology; medicinal chemistry; antioxidant activity; redox process; antioxidant; lipid peroxidation

Special Issue Information

Dear Colleagues,

Most of the events occurring in biological systems in both plants and humans’ lives involve redox processes as molecular interactions are conducted by redox and/or acid–base actions in buffered media. Oxidation–reduction (redox) reactions are central to the existence of life. Several decades ago, the notion of oxidative stress emerged and was considered as a key player either in triggering biochemical disruption or in lesser degree for maintaining cellular homeostasis. As a result, mitochondrial dysfunction appears, leading to various diseases. Numerous studies have been reported showing a growing interest in inflammation, which is central in the development of several diseases including atherosclerosis, diabetes and cancer.

To tackle those diseases, there is an urgent need for new scaffold-based compounds designed to modulate enzyme activity, inhibiting bacteria growth and targeting mitochondria. Therefore, numerous chemical families have been developed both on quantitative structure–activity relationship (QSAR) and predictive studies such as computer assistance with pharmacokinetics. Macromolecules, nanoparticles and small compounds, depending on the disease, are good candidates. Also, several types of natural molecules have been isolated to achieve similar goals, i.e., tackling either bacteria involved in malaria or targeting sickle cells disease as well as mitochondrial dysfunction.

Furthermore, alkaline aqueous solutions, in addition to redox active natural compounds or their structural derivatives, can also be potent redox cyclers in microorganisms that participate in the modulation of pathogen growth by disrupting cellular redox homeostasis or the function of redox-sensitive cellular components.

This Special Issue aims to bring together researchers from various chemical specialties (pure synthesis, electrochemistry and medicinal chemistry, including pharmacognosy) to take part into the discovery of new redox drugs able to tackle diseases involving oxidative processes. A better understanding of the molecular and cellular basis of redox biology will help to achieve this goal with novel redox medicine approaches.

Dr. Ange Mouithys-Mickalad
Guest Editor

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Keywords

  • redox-active Molecules
  • oxidative stress
  • inflammatory diseases
  • QSAR
  • computer-aided drug design
  • redox active natural compounds

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Published Papers (3 papers)

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Research

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39 pages, 6007 KB  
Article
Kratom (Mitragyna speciosa) as a Phytochemical-Based Natural Product Exhibiting Opioid-like Analgesic Effects with Reduced Tolerance and Dependence Liability via TLR4-Associated Neuroimmune Modulation
by Fajar Prasetya, Niken Indriyanti, Nurul Muhlisa Mus, Mentarry Bafadal, Raisa Fadilla, Yuli Widiyastuti, Chaidir Chaidir, Hadi Kuncoro, Sofa Fajriah, Rudi Heryanto, Angga Cipta Narsa, Onny Ziasti Fricillia, Yurika Sastyarina, Victoria Yulita Fitriani, Siti Rouchmana, Nurus Sobah, Zulhaerana Bahar, Nur Rezky Khairun Nisaa, Helmi Helmi and Hady Anshory
Molecules 2026, 31(9), 1428; https://doi.org/10.3390/molecules31091428 - 26 Apr 2026
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Abstract
Kratom (Mitragyna speciosa) is a botanical candidate for pain management with potentially reduced opioid-related risks, partly through modulation of neuroimmune pathways involving Toll-Like Receptor 4 (TLR4). This study aimed to characterize the phytochemical profile of kratom ethanol extract and evaluate its [...] Read more.
Kratom (Mitragyna speciosa) is a botanical candidate for pain management with potentially reduced opioid-related risks, partly through modulation of neuroimmune pathways involving Toll-Like Receptor 4 (TLR4). This study aimed to characterize the phytochemical profile of kratom ethanol extract and evaluate its effects on TLR4 signalling, neuroinflammatory cytokines, analgesic activity, withdrawal behaviours, and organ safety in morphine-dependent mice. Metabolite profiling was conducted using UHPLC–Q-Exactive Orbitrap HRMS, followed by molecular docking of major constituents to the TLR4 complex. In vivo assessments included flow cytometry and gene expression analyses of TLR4-mediated cytokines (NF-κB, IL-1β, IL-6), behavioural assays for antinociception, endurance, and withdrawal symptoms, and histopathological and biochemical evaluation of liver, kidney, and spleen tissues. More than 100 metabolites were identified, including mitragynine and flavonoids such as rutin and isoquercetin, which showed interactions with key TLR4 residues. Selected fractions suppressed pro-inflammatory cytokine expression, increased tail-pinch latency comparable to morphine, reduced withdrawal manifestations, and demonstrated nephroprotective and immunomodulatory effects, although mild reversible hepatic alterations were observed in specific fractions. Overall, kratom ethanol extract exhibited fraction-dependent analgesic and anti-neuroinflammatory activities associated with TLR4 modulation, supporting its potential as a botanical analgesic candidate while emphasizing the importance of safety optimization and standardized fraction development. Full article
(This article belongs to the Special Issue Redox-Active Molecules as Key Players for Inflammatory Diseases)
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10 pages, 818 KB  
Article
Aldose Reductase Inhibition by Orthosiphon stamineus Extracts and Constituents Suggests Antioxidant Potential
by Yousaf Dawood, Atheer Zgair, Mun Fei Yam and Nur Hidayah Kaz Abdul Aziz
Molecules 2025, 30(23), 4637; https://doi.org/10.3390/molecules30234637 - 2 Dec 2025
Cited by 2 | Viewed by 894
Abstract
Background/Objectives: Aldose reductase (AR) plays a crucial role in the accumulation of oxidative factors that lead to oxidative stress-related neuroinflammation. This study aims to find a novel agent from natural sources that can inhibit AR. Methods: Different extracts of Orthosiphon stamineus Benth (OS) [...] Read more.
Background/Objectives: Aldose reductase (AR) plays a crucial role in the accumulation of oxidative factors that lead to oxidative stress-related neuroinflammation. This study aims to find a novel agent from natural sources that can inhibit AR. Methods: Different extracts of Orthosiphon stamineus Benth (OS) leaves and its active constituents, eupatorin (EUP), rosmarinic acid (RA), sinensetin (SEN) and 3-hydroxy-5,6,7,4-tetramethoxyflavone (TMF), were used to identify the potential inhibition effect of AR. A new high-performance liquid chromatography (HPLC) method was developed to determine these phytochemicals using the Shimadzu LC-20AD HPLC system. In addition, the in vitro inhibition effect of OS ethanol extracts (95% and 50%) and OS components EUP, RA, and SEN was investigated in recombinant AR (AKR1B1). Results: In this study, the developed HPLC method was precise and accurate, and demonstrated clear separation of the four compounds—EUP, RA, SEN, and TMF—in the ethanolic extract. The contents of the four selected compounds—EUP, RA, SEN, and TMF—in 95% ethanolic extract were 2.35, 11.91, 0.94, and 0.18%, respectively. RA showed the highest concentration among the selected compounds, indicating that RA is the major constituent of this plant. The in vitro assay showed significant inhibition of the AR enzyme by RA and OS ethanol extracts 95% and 50% (IC50: 41.42 µM; 63.42 µg/mL and 93.22 µg/mL, respectively). Conclusions: The ethanolic extract of OS and RA could be a promising therapeutics option for the treatment of oxidative stress-related neuroinflammation disorders by inhibiting AR. Full article
(This article belongs to the Special Issue Redox-Active Molecules as Key Players for Inflammatory Diseases)
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Review

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19 pages, 16214 KB  
Review
N-Acetyl-L-Cysteine as a Potential Adjunctive Strategy in STEC-HUS: Mechanistic Rationale and Current Evidence
by Joanna Wróblewska, Marcin Wróblewski and Alina Woźniak
Molecules 2026, 31(13), 2264; https://doi.org/10.3390/molecules31132264 - 29 Jun 2026
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Abstract
Shiga toxin-producing Escherichia coli (STEC) infections are a major cause of hemolytic uremic syndrome (HUS), a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The pathogenesis of STEC-HUS is primarily driven by Shiga toxins (Stx), which induce endothelial injury, [...] Read more.
Shiga toxin-producing Escherichia coli (STEC) infections are a major cause of hemolytic uremic syndrome (HUS), a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The pathogenesis of STEC-HUS is primarily driven by Shiga toxins (Stx), which induce endothelial injury, inflammation, platelet activation, and microvascular thrombosis. Hemolysis associated with thrombotic microangiopathy leads to the release of hemoglobin and free heme into the circulation. Free heme, an iron-containing molecule with potent pro-oxidative, pro-inflammatory, and cytotoxic properties, contributes to oxidative stress, endothelial dysfunction, complement activation, and further tissue injury. Oxidative stress plays a crucial role in both host and bacterial cells, influencing disease progression and the expression of bacterial virulence factors, including Shiga toxin. N-acetyl-L-cysteine (NAC), a precursor of glutathione (GSH) and a well-established antioxidant, has attracted attention as a potential adjunctive therapeutic agent due to its antioxidant, anti-inflammatory, antiplatelet, and cytoprotective properties. In addition, NAC may influence iron- and heme-mediated oxidative damage and improve erythrocyte resistance to oxidative stress. This review summarizes current knowledge regarding the roles of oxidative stress and free heme in STEC-HUS and examines the mechanistic rationale and current evidence supporting NAC as a potential adjunctive strategy. The available evidence remains largely indirect and preclinical; therefore, the potential role of NAC in STEC-HUS should be considered hypothesis-generating and requires further investigation in clinical studies. Full article
(This article belongs to the Special Issue Redox-Active Molecules as Key Players for Inflammatory Diseases)
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