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Effects of Bioactive Compounds in Oxidative Stress and Inflammation

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 11921

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Dr. Paul-Mihai Boarescu

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Guest Editor

Department of Biomedical Sciences, Faculty of Medicine and Biological Sciences, “Ștefan cel Mare” University of Suceava, 720229 Suceava, Romania
Interests: oxidative stress; inflammation; bioactive compounds; cardiovascular diseases

Dr. Raluca Maria Pop

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Guest Editor

Department of Pharmacology, Toxicology and Clinical Pharmacology, University of Medicine and Pharmacy Iuliu Hatieganu Cluj-Napoca, Victor Babes, 8, 400000 Cluj-Napoca, Romania
Interests: spectroscopy; chromatography; mass spectrometry; plant bioactive compounds; antioxidant activity; oxidative stress and inflammation; cardiovascular diseases
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Dear Colleagues,

Oxidative stress and inflammation play important roles in the pathogenesis of different diseases. However, the difficulty in controlling these pathophysiological processes has encouraged researchers to investigate potential bioactive compounds with anti-inflammatory and antioxidant effects.

Bioactive compounds have emerged as key food components related to healthy status and disease prevention, as they are a promising alternative for disease prevention and treatment, in some cases. Although a great number of bioactive compounds have already been isolated and investigated, nature is still an endless source of medical drugs with anti-inflammatory and/or antioxidant properties that are waiting to be discovered.

This Special Issue may publish original research papers and reviews on aspects related to the anti-inflammatory and/or antioxidant properties of different bioactive compounds, focusing on their molecular mechanisms.

Dr. Paul-Mihai Boarescu
Dr. Raluca Maria Pop
Guest Editors

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Keywords

natural products
antioxidant effects
anti-inflammatory effects
molecular targets
health beneficial effect
bioactive compounds

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Published Papers (7 papers)

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Research

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19 pages, 1630 KiB

Open AccessArticle

A Plant-Based Dietary Supplement Exhibits Significant Effects on Markers of Oxidative Stress, Inflammation, and Immune Response in Subjects Recovering from Respiratory Viral Infection: A Randomized, Double-Blind Clinical Study Using Vitamin C as a Positive Control

by Bruno Fink, John M. Hunter, Zbigniew Pietrzkowski, Richard Fink, Coy Brunssen, Henning Morawietz and Boris Nemzer

Int. J. Mol. Sci. 2025, 26(11), 5209; https://doi.org/10.3390/ijms26115209 - 29 May 2025

Abstract

Respiratory viruses continue to present serious health challenges to human wellness. Growing evidence suggests that the more severe and damaging effects and symptoms of influenza, rhinovirus (RV), respiratory syncytial virus (RSV), and COVID-19 may primarily result from their common ability to disorganize the body’s healthy immune response. The simultaneous over-stimulation of several reactive oxygen species (ROS) pathways and concurrent suppression of bioavailable Nitic Oxide (NO) contribute to an immune disbalance that can lead to cellular oxidative distress and an excessive inflammatory response. This study evaluated the real-time, acute ability of a single, orally administered 50 mg encapsulated dose of a plant-based dietary supplement (“PB-Blend”), compared to 1000 mg of Vitamin C as a positive control, to modulate multiple ROS associated with a dampened immune response, as well as NO and other markers of inflammation, in a cohort recovering from a moderate course of COVID-19. This randomized, double-blind study was performed on 28 individuals 18–24 days after a moderate COVID-19 infection. Participants were orally supplemented with a single encapsulated dose of either 50 mg of PB-Blend or 1000 mg Vitamin C as a positive control. Changes in the levels of bioavailable NO (measured as circulating NOHb) were assessed, as well as the ex vivo cellular formation of mitochondrial, NOX2-, iNOS-, and TNFα-dependent ROS. All parameters were measured in real time before ingestion (baseline), and then at 30, 60, 120, and 180 min after administration. ROS were measured using a portable electron paramagnetic resonance (EPR) spectrometer. Inflammatory, immunity (hsCRP and TNFα plasma levels), interleukin (IL1, IL6, IL8, and IL10), cytokine (IFNγ, TNFα, and NF-κB), and immunoglobulin (IgA, IgM, IgG, and IgE) profiles were also followed. In addition to laboratory and cell function investigations, we performed clinical cardio ergometry, blood O₂ saturation, and respirometry examinations. As hypothesized, the collected baseline data from this study group confirmed that mitochondrial, NOX2, and iNOS enzymatic systems were strongly involved in the generation of ROS at 18–24 days following a positive COVID-19 PCR test. Acute single-dose supplementation of 50 mg PB-Blend had a multifunctional impact on ROS and significantly inhibited the following: (a.) mitochondrial ROS levels by up to 56%; (b.) iNOS by up to 60%; and (c.) NOX2-dependent ROS generation by up to 49%. Moreover, 1000 mg Vitamin C supplementation exhibited narrower ROS-mitigating activity by solely inhibiting NOX2-dependent ROS generation by 45%. Circulating NOHb levels were significantly increased after PB-Blend administration (33%), but not after Vitamin C administration. PB-Blend and Vitamin C exhibited similar potential to reduce ex vivo high dose TNFα (200 ng/mL)-induced H₂O₂ formation. These results suggest that 50 mg of PB-Blend has the potential to modulate disbalanced mitochondria, iNOS, and NOX2 enzymatic systems that can be engendered during respiratory viral infection and subsequent recovery. Moreover, PB-Blend, but not Vitamin C, showed potential to upregulate bioavailable NO, which is known to decline under these conditions. Based upon these observations, PB-Blend could be considered an alternative to, or to be used in tandem with Vitamin C in applications that promote immune support and recovery during seasons of heightened respiratory viral risk (e.g., “flu season”). Full article

(This article belongs to the Special Issue Effects of Bioactive Compounds in Oxidative Stress and Inflammation)

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19 pages, 1993 KiB

Open AccessArticle

Anti-Inflammatory and Antioxidant Effects of (6S,9R)-Vomifoliol from Gaultheria procumbens L.: In Vitro and Ex Vivo Study in Human Immune Cell Models

by Piotr Michel, Anna Wajs-Bonikowska, Anna Magiera, Agnieszka Wosiak, Ewa Balcerczak, Monika Ewa Czerwińska and Monika Anna Olszewska

Int. J. Mol. Sci. 2025, 26(4), 1571; https://doi.org/10.3390/ijms26041571 - 13 Feb 2025

Viewed by 765

Abstract

(6S,9R)-vomifoliol (VO) is a natural norisoprenoid of the megastigmane type derived from Gaultheria procumbens, an aromatic, evergreen shrub whose leaves, fruits, and aerial parts are used in traditional phytotherapy to treat oxidative stress and inflammation-related disorders. The plant is known as a rich source of essential oil and polyphenols. However, the levels of other constituents of G. procumbens, including VO, have yet to be explored. There is also a knowledge gap in the pharmacological potential of VO in the context of inflammation. Therefore, the present study aimed to investigate the accumulation of VO in leaves, stems, and fruits of G. procumbens and to determine its antioxidant and anti-inflammatory effects in non-cellular in vitro and cell-based models of human immune cells ex vivo. The GC-FID-MS (gas chromatography coupled with flame ionisation detector and mass spectrometer) analysis revealed the leaves as the richest source of VO (0.36 mg/g dw of the plant material) compared to other G. procumbens organs. In non-cellular activity tests, VO showed comparable to positive control anti-inflammatory activity against lipoxygenase, with significantly weaker impact on hyaluronidase and cyclooxygenase-2, and no effect on cyclooxygenase-1 isozyme. VO at 5–75 μM revealed a significant and dose-dependent ability to reduce the reactive oxygen species (ROS) level, downregulate the release of pro-inflammatory cytokines [tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8), IL-6, and IL-1β] and tissue-remodelling enzymes (elastase-2, metalloproteinase-9), and up-regulate the secretion of anti-inflammatory cytokine IL-10 in bacterial lipopolysaccharide (LPS)- and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-stimulated human neutrophils and peripheral blood mononuclear cells (PBMCs) ex vivo. Furthermore, a significant reduction in IL-6, lipoxygenase (LOX), nuclear factor κ-light-chain-enhancer of activated B cells 1 (NF-κB1), and NF-κB2 gene expression in LPS-stimulated peripheral blood lymphocytes was demonstrated by real-time PCR. The cellular safety of VO at 5–75 μM was confirmed by flow cytometry, with the viability of neutrophils and PBMCs after incubation with VO at 93.8–98.4%. The results encourage further studies of VO as a promising non-cytotoxic natural anti-inflammatory agent and support the use of leaves of G. procumbens in the adjuvant treatment of oxidative stress and inflammation-related diseases of affluence. Full article

(This article belongs to the Special Issue Effects of Bioactive Compounds in Oxidative Stress and Inflammation)

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20 pages, 6142 KiB

Open AccessArticle

Influence of Secondary Metabolites According to Maturation of Perilla (Perilla frutescens) on Respiratory Protective Effect in Fine Particulate Matter (PM2.5)-Induced Human Nasal Cell

by Min-Young Kim, Jung-In Kim, Sang-Woo Kim, Sungup Kim, Eunyoung Oh, Jeongeun Lee, Eunsoo Lee, Yeon-Ju An, Chae-Yeon Han, Heungsu Lee and Myoung-Hee Lee

Int. J. Mol. Sci. 2024, 25(22), 12119; https://doi.org/10.3390/ijms252212119 - 12 Nov 2024

Cited by 2 | Viewed by 893

Abstract

Fine particulate matter (PM2.5) exposure worsens chronic respiratory diseases through oxidative stress and inflammation. Perilla frutescens (L.) has potential respiratory protective properties, but the impact of growth stages on its beneficial metabolites is unclear. We aimed to evaluate how different growth stages affect phenolic acids, flavonoids, and polycosanols in perilla seeds and flowers and their efficacy in countering PM2.5-induced damage. Perilla seeds and flowers from five varieties at 10, 20, 30, and 40 days post-flowering were analyzed for metabolite content. Their antioxidant, anti-inflammatory, and respiratory protective effects were tested in RPMI 2650 cells. Our findings indicated that perilla flowers contained higher levels of functional components than seeds and exhibited significant variation with maturation. Phenolic acids of perilla flowers were highest at the early stages of maturation after flowering. However, individual flavones of perilla flowers were the highest at the late maturation stages after flowering. Extracts from perilla flowers harvested 20 days after flowering exhibited significant respiratory protection, effectively inhibiting inflammatory cytokines, mucus secretion, and oxidative stress markers. In conclusion, the flower parts of perilla, particularly those harvested 20 days after flowering, are useful materials for obtaining phenolic compounds, including rosmarinic acid, with high antioxidant and respiratory enhancement effects. Full article

(This article belongs to the Special Issue Effects of Bioactive Compounds in Oxidative Stress and Inflammation)

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15 pages, 602 KiB

Open AccessArticle

Phytochemical Analysis and Antioxidant Effects of Prunella vulgaris in Experimental Acute Inflammation

by Camelia-Manuela Mîrza, Tudor-Valentin Mîrza, Antonia Cristina Maria Odagiu, Ana Uifălean, Anca Elena But, Alina Elena Pârvu and Adriana-Elena Bulboacă

Int. J. Mol. Sci. 2024, 25(9), 4843; https://doi.org/10.3390/ijms25094843 - 29 Apr 2024

Cited by 7 | Viewed by 1871

Abstract

Prunella vulgaris (PV) is one of the most commonly used nutraceuticals as it has been proven to have anti-inflammatory and antioxidant properties. The aim of this study was to evaluate the phytochemical composition of PV and its in vivo antioxidant properties. A phytochemical analysis measuring the total phenolic content (TPC), the identification of phenolic compounds by HPLC-DAD-ESI, and the evaluation of the in vitro antioxidant activity by the DPPH assay of the extract were performed. The antioxidant effects on inflammation induced by turpentine oil were experimentally tested in rats. Seven groups with six animals each were used: a control group, the experimental inflammation treatment group, the experimental inflammation and diclofenac sodium (DS) treatment group, and four groups with their inflammation treated using different dilutions of the extract. Serum redox balance was assessed based on total oxidative status (TOS), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), total thiols, and an oxidative stress index (OSI) contents. The TPC was 0.28 mg gallic acid equivalents (GAE)/mL extract, while specific representatives were represented by caffeic acid, p-coumaric acid, dihydroxybenzoic acid, gentisic acid, protocatechuic acid, rosmarinic acid, vanillic acid, apigenin–glucuronide, hesperidin, kaempferol–glucuronide. The highest amount (370.45 μg/mL) was reported for hesperidin, which is a phenolic compound belonging to the flavanone subclass. The antioxidant activity of the extracts, determined using the DPPH assay, was 27.52 mmol Trolox/mL extract. The PV treatment reduced the oxidative stress by lowering the TOS, OSI, NO, and MDA and by increasing the TAC and thiols. In acute inflammation, treatment with the PV extract reduced oxidative stress, with lower concentrations being more efficient and having a better effect than DS. Full article

(This article belongs to the Special Issue Effects of Bioactive Compounds in Oxidative Stress and Inflammation)

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Review

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48 pages, 4356 KiB

Open AccessReview

Unlocking the Pharmacological Potential of Myricetin Against Various Pathogenesis

by Saleh A. Almatroodi and Arshad Husain Rahmani

Int. J. Mol. Sci. 2025, 26(9), 4188; https://doi.org/10.3390/ijms26094188 - 28 Apr 2025

Viewed by 502

Abstract

Myricetin is a natural flavonoid with powerful antioxidant and anti-inflammatory potential commonly found in vegetables, fruits, nuts, and tea. The vital role of this flavonoid in the prevention and treatment of various diseases is evidenced by its ability to reduce inflammation and oxidative stress, maintain tissue architecture, and modulate cell signaling pathways. Thus, this review summarizes recent evidence on myricetin, focusing precisely on its mechanisms of action in various pathogenesis, including obesity, diabetes mellitus, arthritis, osteoporosis, liver, neuro, cardio, and reproductive system-associated pathogenesis. Moreover, it has been revealed that myricetin exhibits anti-microbial properties due to obstructive virulence factors, preventing biofilm formation and disrupting membrane integrity. Additionally, synergistic potential with other drugs and the role of myricetin-based nanoformulations in different diseases are properly discussed. This review seeks to increase the understanding of myricetin’s pharmacological potential in various diseases, principally highlighting its effective mechanisms of action. Further wide-ranging research, as well as more randomized and controlled clinical trial studies, should be executed to reconnoiter this compound’s therapeutic value, safety, and usefulness against various human pathogenesis. Full article

(This article belongs to the Special Issue Effects of Bioactive Compounds in Oxidative Stress and Inflammation)

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28 pages, 1219 KiB

Open AccessReview

Antioxidant and Anti-Inflammatory Effects of Bioactive Compounds in Atherosclerosis

by Ştefan Horia Roşian, Ioana Boarescu and Paul-Mihai Boarescu

Int. J. Mol. Sci. 2025, 26(3), 1379; https://doi.org/10.3390/ijms26031379 - 6 Feb 2025

Cited by 6 | Viewed by 2865

Abstract

Atherosclerosis, a chronic inflammatory disease characterized by the accumulation of lipids and immune cells within arterial walls, remains a leading cause of cardiovascular morbidity and mortality worldwide. Oxidative stress and inflammation are central to its pathogenesis, driving endothelial dysfunction, foam cell formation, and plaque instability. Emerging evidence highlights the potential of bioactive compounds with antioxidant and anti-inflammatory properties to mitigate these processes and promote vascular health. This review explores the mechanisms through which bioactive compounds—such as polyphenols, carotenoids, flavonoids, omega-3 fatty acids, coenzyme Q10, and other natural compounds—modulate oxidative stress and inflammation in atherosclerosis. It examines their effects on key molecular pathways, including the inhibition of reactive oxygen species (ROS) production, suppression of nuclear factor-κB (NF-κB), and modulation of inflammatory cytokines. By integrating current knowledge, this review underscores the therapeutic potential of dietary and supplemental bioactive compounds as complementary strategies for managing atherosclerosis, paving the way for future research and clinical applications. Full article

(This article belongs to the Special Issue Effects of Bioactive Compounds in Oxidative Stress and Inflammation)

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32 pages, 2112 KiB

Open AccessReview

Antioxidant Role of Probiotics in Inflammation-Induced Colorectal Cancer

by Sevag Hamamah, Andrei Lobiuc and Mihai Covasa

Int. J. Mol. Sci. 2024, 25(16), 9026; https://doi.org/10.3390/ijms25169026 - 20 Aug 2024

Cited by 4 | Viewed by 3031

Abstract

Colorectal cancer (CRC) continues to be a significant contributor to global morbidity and mortality. Emerging evidence indicates that disturbances in gut microbial composition, the formation of reactive oxygen species (ROS), and the resulting inflammation can lead to DNA damage, driving the pathogenesis and progression of CRC. Notably, bacterial metabolites can either protect against or contribute to oxidative stress by modulating the activity of antioxidant enzymes and influencing signaling pathways that govern ROS-induced inflammation. Additionally, microbiota byproducts, when supplemented through probiotics, can affect tumor microenvironments to enhance treatment efficacy and selectively mediate the ROS-induced destruction of CRC cells. This review aims to discuss the mechanisms by which taxonomical shifts in gut microbiota and related metabolites such as short-chain fatty acids, secondary bile acids, and trimethylamine-N-oxide influence ROS concentrations to safeguard or promote the onset of inflammation-mediated CRC. Additionally, we focus on the role of probiotic species in modulating ROS-mediated signaling pathways that influence both oxidative status and inflammation, such as Nrf2-Keap1, NF-κB, and NLRP3 to mitigate carcinogenesis. Overall, a deeper understanding of the role of gut microbiota on oxidative stress may aid in delaying or preventing the onset of CRC and offer new avenues for adjunct, CRC-specific therapeutic interventions such as cancer immunotherapy. Full article

(This article belongs to the Special Issue Effects of Bioactive Compounds in Oxidative Stress and Inflammation)

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