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Natural Bioactives and Inflammation, 2nd Edition
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Natural Bioactives and Inflammation, 2nd Edition

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: 30 April 2025 | Viewed by 7700

Special Issue Editor

Dr. Juan Gambini

E-Mail Website
Guest Editor
Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, E46010 Valencia, Spain
Interests: nutrition; longevity; aging; oxidative stress and exercise
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to our Special Issue of the International Journal of Molecular Sciences (IJMS), entitled “Natural Bioactives and Inflammation, 2nd Edition”.

Inflammation is a key physiological process in tissue repair and immunity against infections, trauma, toxins, or allergic reactions. However, chronic inflammation can cause the development of diseases such as cardiovascular disease, autoimmune disease, neurological disease, and cancer. Bioactive compounds, such as polyphenols, omega fatty acids, etc., are molecules that present therapeutic potential by reducing inflammation, thereby decreasing the risk of chronic diseases. As inflammation regulation is one of the keys to longevity, by consuming these bioactive compounds, we could potentially increase both our health- and lifespan.

For this Special Issue, we want to collect recent research topics and current review articles, to report the latest updates on inflammation and how to modulate it using natural bioactive compounds.

Dr. Juan Gambini
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • inflammation
  • bioactive compounds
  • polyphenols
  • nutraceutical
  • diet
  • nutrition
  • pharmacology
  • health
  • lifespan
  • healthspan
  • aging
  • inflammaging

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Published Papers (5 papers)

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Research

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20 pages, 16775 KiB  
Article
Galangin’s Neuroprotective Role: Targeting Oxidative Stress, Inflammation, and Apoptosis in Ischemic Stroke in a Rat Model of Permanent Middle Cerebral Artery Occlusion
by Nut Palachai, Araya Supawat, Ratchaniporn Kongsui, Lars Klimaschewski and Jinatta Jittiwat
Int. J. Mol. Sci. 2025, 26(5), 1847; https://doi.org/10.3390/ijms26051847 - 21 Feb 2025
Viewed by 649
Abstract
The rising incidence of ischemic stroke poses significant health and healthcare burdens. Given the limitations of current therapeutic options, there is increasing interest in exploring the potential of galangin, a natural flavonoid compound, as a treatment for ischemic stroke. This study aimed to [...] Read more.
The rising incidence of ischemic stroke poses significant health and healthcare burdens. Given the limitations of current therapeutic options, there is increasing interest in exploring the potential of galangin, a natural flavonoid compound, as a treatment for ischemic stroke. This study aimed to evaluate the neuroprotective effects and underlying mechanisms of galangin in mitigating oxidative stress, inflammation, and apoptosis in a rat model of permanent cerebral ischemia. Sixty male Wistar rats were divided into six groups: control; right middle cerebral artery occlusion (Rt.MCAO) with vehicle; Rt.MCAO with piracetam, a synthetic compound known as a cognitive enhancer; and Rt.MCAO with galangin administered at doses of 25, 50, and 100 mg/kg body weight. Neurological deficit scores, brain edema, neuronal density, and microglial morphology were assessed along with the activity of myeloperoxidase (MPO), a marker of inflammation, and superoxide dismutase (SOD). Additionally, the expression of key markers for inflammation and apoptosis, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), Bcl-2-associated X protein (Bax), B-cell lymphoma-extra large (Bcl-XL), and caspase-3, was analyzed to elucidate potential mechanisms. The results demonstrated that galangin treatment significantly improved neurological deficit scores, reduced brain edema, enhanced neuronal density, attenuated microglial activation, decreased MPO activity, and increased SOD activity in both the cortex and hippocampus, highlighting its neuroprotective potential. These effects were linked to the modulation of inflammatory and apoptotic pathways. Specifically, galangin significantly reduced the expression of IL-6, COX-2, Bax, and caspase-3 while increasing the levels of the anti-apoptotic protein Bcl-XL. In conclusion, galangin demonstrates significant promise as a neuroprotective agent for ischemic stroke by suppressing inflammation and apoptosis, thereby improving neurological outcomes. However, clinical trials are required to validate these preclinical findings and confirm galangin’s therapeutic efficacy in humans. Full article
(This article belongs to the Special Issue Natural Bioactives and Inflammation, 2nd Edition)
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11 pages, 1896 KiB  
Communication
Nobiletin and Eriodictyol Suppress Release of IL-1β, CXCL8, IL-6, and MMP-9 from LPS, SARS-CoV-2 Spike Protein, and Ochratoxin A-Stimulated Human Microglia
by Irene Tsilioni, Duraisamy Kempuraj and Theoharis C. Theoharides
Int. J. Mol. Sci. 2025, 26(2), 636; https://doi.org/10.3390/ijms26020636 - 14 Jan 2025
Viewed by 1855
Abstract
Neuroinflammation is involved in various neurological and neurodegenerative disorders in which the activation of microglia is one of the key factors. In this study, we examined the anti-inflammatory effects of the flavonoids nobiletin (5,6,7,8,3′,4′-hexamethoxyflavone) and eriodictyol (3′,4′,5,7-tetraxydroxyflavanone) on human microglia cell line activation [...] Read more.
Neuroinflammation is involved in various neurological and neurodegenerative disorders in which the activation of microglia is one of the key factors. In this study, we examined the anti-inflammatory effects of the flavonoids nobiletin (5,6,7,8,3′,4′-hexamethoxyflavone) and eriodictyol (3′,4′,5,7-tetraxydroxyflavanone) on human microglia cell line activation stimulated by either lipopolysaccharide (LPS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length Spike protein (FL-Spike), or the mycotoxin ochratoxin A (OTA). Human microglia were preincubated with the flavonoids (10, 50, and 100 µM) for 2 h, following which, they were stimulated for 24 h. The inflammatory mediators interleukin-1 beta (IL-1β), chemokine (C-X-C motif) ligand 8 (CXCL8), IL-6, and matrix metalloproteinase-9 (MMP-9) were quantified in the cell culture supernatant by enzyme-linked immunosorbent assay (ELISA). Both nobiletin and eriodictyol significantly inhibited the LPS, FL-Spike, and OTA-stimulated release of IL-1β, CXCL8, IL-6, and MMP-9 at 50 and 100 µM, while, in most cases, nobiletin was also effective at 10 µM, with the most pronounced reductions at 100 µM. These findings suggest that both nobiletin and eriodictyol are potent inhibitors of the pathogen-stimulated microglial release of inflammatory mediators, highlighting their potential for therapeutic application in neuroinflammatory diseases, such as long COVID. Full article
(This article belongs to the Special Issue Natural Bioactives and Inflammation, 2nd Edition)
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18 pages, 3525 KiB  
Article
Molecular Insights into the Inhibition of Lipid Accumulation in Hepatocytes by Unique Extracts of Ashwagandha
by Dongyang Li, Hanlin Han, Yixin Sun, Huayue Zhang, Ren Yoshitomi, Sunil C. Kaul and Renu Wadhwa
Int. J. Mol. Sci. 2024, 25(22), 12256; https://doi.org/10.3390/ijms252212256 - 14 Nov 2024
Viewed by 1485
Abstract
We investigated the effect of purified withanolides and extracts derived from Ashwagandha on steatosis, the abnormal accumulation of fat that can lead to non-alcoholic fatty liver disease (NAFLD). Collaborator of ARF (CARF, also known as CDKN2AIP, a protein that regulates hepatic lipid metabolism, [...] Read more.
We investigated the effect of purified withanolides and extracts derived from Ashwagandha on steatosis, the abnormal accumulation of fat that can lead to non-alcoholic fatty liver disease (NAFLD). Collaborator of ARF (CARF, also known as CDKN2AIP, a protein that regulates hepatic lipid metabolism, fat buildup, and liver damage) was used as an indicator. Six withanolides (Withaferin A, Withanone, Withanolide B, Withanoside IV, Withanoside V, and Withanostraminolide-12 deoxy) reversed the decrease in CARF caused by exposure to free fatty acids (FFAs) in liver-derived cells (HepG2 hepatocytes). After analyzing the effects of these withanolides on CARF mRNA and protein levels, FFA accumulation, protein aggregation, and oxidative and DNA damage stresses, we selected Withaferin A and Withanone for molecular analyses. Using the palmitic-acid-induced fatty acid accumulation stress model in Huh7 cells, we found a significant reduction in the activity of the key regulators of lipogenesis pathways, including sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and peroxisome proliferator-activated receptors (PPARγ and PPARα). This in vitro study suggests that low, non-toxic doses of Withaferin A, Withanone, or Ashwagandha extracts containing these withanolides possess anti-steatosis and antioxidative-stress properties. Further in vivo and clinical studies are required to investigate the therapeutic potential of these Ashwagandha-derived bioactive ingredients for NAFLD. Full article
(This article belongs to the Special Issue Natural Bioactives and Inflammation, 2nd Edition)
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15 pages, 3119 KiB  
Article
Anti-Neuroinflammatory Effects of Ginkgo biloba Extract EGb 761 in LPS-Activated BV2 Microglial Cells
by Lu Sun, Matthias Apweiler, Ashwini Tirkey, Dominik Klett, Claus Normann, Gunnar P. H. Dietz, Martin D. Lehner and Bernd L. Fiebich
Int. J. Mol. Sci. 2024, 25(15), 8108; https://doi.org/10.3390/ijms25158108 - 25 Jul 2024
Cited by 3 | Viewed by 2695
Abstract
Inflammatory processes in the brain can exert important neuroprotective functions. However, in neurological and psychiatric disorders, it is often detrimental due to chronic microglial over-activation and the dysregulation of cytokines and chemokines. Growing evidence indicates the emerging yet prominent pathophysiological role of neuroinflammation [...] Read more.
Inflammatory processes in the brain can exert important neuroprotective functions. However, in neurological and psychiatric disorders, it is often detrimental due to chronic microglial over-activation and the dysregulation of cytokines and chemokines. Growing evidence indicates the emerging yet prominent pathophysiological role of neuroinflammation in the development and progression of these disorders. Despite recent advances, there is still a pressing need for effective therapies, and targeting neuroinflammation is a promising approach. Therefore, in this study, we investigated the anti-neuroinflammatory potential of a marketed and quantified proprietary herbal extract of Ginkgo biloba leaves called EGb 761 (10–500 µg/mL) in BV2 microglial cells stimulated by LPS (10 ng/mL). Our results demonstrate significant inhibition of LPS-induced expression and release of cytokines tumor necrosis factor-α (TNF-α) and Interleukin 6 (IL-6) and chemokines C-X-C motif chemokine ligand 2 (CXCL2), CXCL10, c-c motif chemokine ligand 2 (CCL2) and CCL3 in BV2 microglial cells. The observed effects are possibly mediated by the mitogen-activated protein kinases (MAPK), p38 MAPK and ERK1/2, as well as the protein kinase C (PKC) and the nuclear factor (NF)-κB signaling cascades. The findings of this in vitro study highlight the anti-inflammatory properties of EGb 761 and its therapeutic potential, making it an emerging candidate for the treatment of neuroinflammatory diseases and warranting further research in pre-clinical and clinical settings. Full article
(This article belongs to the Special Issue Natural Bioactives and Inflammation, 2nd Edition)
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Review

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20 pages, 9476 KiB  
Review
Flavonoids from Scutellaria baicalensis: Promising Alternatives for Enhancing Swine Production and Health
by Jing Wu, Yueqin Qiu, Min Tian, Li Wang, Kaiguo Gao, Xuefen Yang and Zongyong Jiang
Int. J. Mol. Sci. 2025, 26(8), 3703; https://doi.org/10.3390/ijms26083703 - 14 Apr 2025
Viewed by 314
Abstract
Concerns over vaccine safety, bacterial resistance, and drug residues have led to increased interest in plant extracts for improving swine nutrition and health. Scutellaria baicalensis Georgi, rich in four primary flavonoids—baicalin, baicalein, wogonoside, and wogonin—demonstrates significant pharmacological properties, including anti-inflammatory, antioxidant, antibacterial, and [...] Read more.
Concerns over vaccine safety, bacterial resistance, and drug residues have led to increased interest in plant extracts for improving swine nutrition and health. Scutellaria baicalensis Georgi, rich in four primary flavonoids—baicalin, baicalein, wogonoside, and wogonin—demonstrates significant pharmacological properties, including anti-inflammatory, antioxidant, antibacterial, and antiviral activities in swine. These flavonoids have been shown to enhance growth performance, improve immunity, modulate gut microbiota, and aid in the prevention and treatment of various diseases. This review highlights the pharmacological effects of these flavonoids in swine, with a focus on network pharmacology to reveal the underlying molecular mechanisms. By constructing drug-target networks and identifying key signaling pathways, the review reveals how these flavonoids interact with biological systems to promote health. Furthermore, it discusses the practical applications of Scutellaria baicalensis flavonoids in swine production and outlines potential future research directions. This work provides a theoretical framework for understanding the therapeutic targets of these flavonoids, offering valuable insights for advancing sustainable and healthy pig farming practices. Full article
(This article belongs to the Special Issue Natural Bioactives and Inflammation, 2nd Edition)
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