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Molecular Mechanisms of Anti-inflammatory Phytochemicals
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Molecular Mechanisms of Anti-inflammatory Phytochemicals

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: closed (31 March 2022) | Viewed by 21148

Special Issue Editors

Dr. Sanguine Byun

E-Mail Website
Guest Editor
Department of Biotechnology, Yonsei University, Seoul, Korea
Interests: bioactive compounds; functional food; cell signaling
Prof. Dr. Natália Cruz-Martins

E-Mail Website
Guest Editor
1. Faculty of Medicine, University of Porto, 4099-002 Porto, Portugal
2. Institute for Research and Innovation in Health (i3S), University of Porto, 4099-002 Porto, Portugal
3. Institute of Research and Advanced Training in Health Sciences and Technologies, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal
4. TOXRUN - Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal
Interests: evidence-based medicine; phytochemistry; phytopharmacology; drug discovery; natural products biochemistry; bioactive molecules; functional foods; nutraceuticals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Inflammation is a normal biological process characterized by the activation of immune and non-immune cells to provide defense against infection and promote tissue repair. However, it is becoming increasingly clear that inflammation also plays a crucial role in the development and progression of many chronic diseases, including cancer, diabetes, cardiovascular diseases, arthritis, asthma, neurodegenerative disorders, and autoimmune diseases. This provides the rationale to develop agents that can target inflammation for the prevention and treatment of chronic diseases.

Phytochemicals are non-nutritive plant-derived compounds that represent a large library of bioactive molecules. Due to their diverse structures and cellular targets, phytochemicals provide broad therapeutic opportunities. Recent studies have discovered the potential of phytochemicals to block key steps in the pathogenesis of inflammatory diseases.

This Special Issue, “Molecular Mechanisms of Anti-Inflammatory Phytochemicals” will include in vitro, in vivo, and clinical studies on the anti-inflammatory effects and molecular mechanisms of phytochemicals, including therapeutic applications in chronic diseases, modes of action, target identification, structure-activity relationships, and identification and quantification of phytochemicals from new sources. Original research articles or reviews in this field are welcome.

Dr. Sanguine Byun
Prof. Dr. Natália Cruz-Martins
Guest Editors

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

  • phytochemicals
  • inflammation
  • molecular mechanism
  • chronic diseases
  • inflammatory diseases
  • cell signaling
  • bioactivity

Published Papers (6 papers)

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Editorial

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3 pages, 213 KiB  
Editorial
Molecular Mechanisms of Anti-Inflammatory Phytochemicals
by Natália Cruz-Martins
Int. J. Mol. Sci. 2022, 23(19), 11016; https://doi.org/10.3390/ijms231911016 - 20 Sep 2022
Cited by 4 | Viewed by 1175
Abstract
Naturally occurring bioactives, also known as phytochemicals, have been widely recognized and researched owing to their multiple potentialities [...] Full article
(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals)

Research

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12 pages, 32332 KiB  
Article
Anti-Inflammatory Activity of Three Triterpene from Hippophae rhamnoides L. in Lipopolysaccharide-Stimulated RAW264.7 Cells
by Yu Han, Chen Yuan, Xiaowei Zhou, Yingjie Han, Yanhao He, Jian Ouyang, Wenna Zhou, Zhenhua Wang, Honglun Wang and Gang Li
Int. J. Mol. Sci. 2021, 22(21), 12009; https://doi.org/10.3390/ijms222112009 - 05 Nov 2021
Cited by 27 | Viewed by 3373
Abstract
Oleanolic acid (OA), asiatic acid (AA), and maslinic acid (MA) are ubiquitous isomeric triterpene phytochemicals with many pharmacological effects. To improve their application value, we used lipopolysaccharide (LPS) to induce RAW264.7 cells and studied the differences in the anti-inflammatory effects of the triterpenes [...] Read more.
Oleanolic acid (OA), asiatic acid (AA), and maslinic acid (MA) are ubiquitous isomeric triterpene phytochemicals with many pharmacological effects. To improve their application value, we used lipopolysaccharide (LPS) to induce RAW264.7 cells and studied the differences in the anti-inflammatory effects of the triterpenes according to their structural differences. MTT, Griess, and immunofluorescence assays, ELISA, flow cytometry, and Western blotting, were performed. The release of LPS-induced pro-inflammatory mediators, such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), and interleukin (IL-6), was significantly inhibited by OA, AA, and MA at the same concentration, and AA and MA promoted the production of anti-inflammatory factor IL-10. OA, AA, and MA inhibited LPS-induced NF-κB nuclear translocation in RAW264.7 cells. OA and AA inhibited the phosphorylation of ERK1/2, P38, and JNK1/2 in LPS-stimulated RAW264.7 cells. Moreover, OA increased LPS-induced Nrf2 expression and decreased Keap1 expression in RAW264.7 cells. OA, AA, and MA inhibited LPS-stimulated intracellular reactive oxygen species (ROS) production and alleviated mitochondrial membrane potential depletion. Overall, our data suggested that OA, AA, and MA exhibited significant anti-inflammatory effects in vitro. In particular, OA and AA take effects through the MAPKs, NF-κB, and Nrf2 signaling pathways. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals)
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16 pages, 2010 KiB  
Article
Comparative Anti-Inflammatory Effects of Salix Cortex Extracts and Acetylsalicylic Acid in SARS-CoV-2 Peptide and LPS-Activated Human In Vitro Systems
by Nguyen Phan Khoi Le, Corinna Herz, João Victor Dutra Gomes, Nadja Förster, Kyriaki Antoniadou, Verena Karolin Mittermeier-Kleßinger, Inga Mewis, Corinna Dawid, Christian Ulrichs and Evelyn Lamy
Int. J. Mol. Sci. 2021, 22(13), 6766; https://doi.org/10.3390/ijms22136766 - 23 Jun 2021
Cited by 18 | Viewed by 4020
Abstract
The usefulness of anti-inflammatory drugs as an adjunct therapy to improve outcomes in COVID-19 patients is intensely discussed. Willow bark (Salix cortex) has been used for centuries to relieve pain, inflammation, and fever. Its main active ingredient, salicin, is metabolized in the [...] Read more.
The usefulness of anti-inflammatory drugs as an adjunct therapy to improve outcomes in COVID-19 patients is intensely discussed. Willow bark (Salix cortex) has been used for centuries to relieve pain, inflammation, and fever. Its main active ingredient, salicin, is metabolized in the human body into salicylic acid, the precursor of the commonly used pain drug acetylsalicylic acid (ASA). Here, we report on the in vitro anti-inflammatory efficacy of two methanolic Salix extracts, standardized to phenolic compounds, in comparison to ASA in the context of a SARS-CoV-2 peptide challenge. Using SARS-CoV-2 peptide/IL-1β- or LPS-activated human PBMCs and an inflammatory intestinal Caco-2/HT29-MTX co-culture, Salix extracts, and ASA concentration-dependently suppressed prostaglandin E2 (PGE2), a principal mediator of inflammation. The inhibition of COX-2 enzyme activity, but not protein expression was observed for ASA and one Salix extract. In activated PBMCs, the suppression of relevant cytokines (i.e., IL-6, IL-1β, and IL-10) was seen for both Salix extracts. The anti-inflammatory capacity of Salix extracts was still retained after transepithelial passage and liver cell metabolism in an advanced co-culture model system consisting of intestinal Caco-2/HT29-MTX cells and differentiated hepatocyte-like HepaRG cells. Taken together, our in vitro data suggest that Salix extracts might present an additional anti-inflammatory treatment option in the context of SARS-CoV-2 peptides challenge; however, more confirmatory data are needed. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals)
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17 pages, 2275 KiB  
Article
Lycopene Inhibits Oxidative Stress-Mediated Inflammatory Responses in Ethanol/Palmitoleic Acid-Stimulated Pancreatic Acinar AR42J Cells
by Jaeeun Lee, Joo Weon Lim and Hyeyoung Kim
Int. J. Mol. Sci. 2021, 22(4), 2101; https://doi.org/10.3390/ijms22042101 - 20 Feb 2021
Cited by 25 | Viewed by 2520
Abstract
High alcohol intake results in the accumulation of non-oxidative ethanol metabolites such as fatty acid ethyl esters (FAEEs) in the pancreas. High FAEE concentrations mediate pancreatic acinar cell injury and are associated with alcoholic pancreatitis. Treatment with ethanol and the fatty acid palmitoleic [...] Read more.
High alcohol intake results in the accumulation of non-oxidative ethanol metabolites such as fatty acid ethyl esters (FAEEs) in the pancreas. High FAEE concentrations mediate pancreatic acinar cell injury and are associated with alcoholic pancreatitis. Treatment with ethanol and the fatty acid palmitoleic acid (EtOH/POA) increased the levels of palmitoleic acid ethyl ester and induced zymogen activation and cytokine expression in pancreatic acinar cells. EtOH/POA induces nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species (ROS) production and pancreatic acinar cell injury. Lycopene, a bright-red carotenoid, is a potent antioxidant due to its high number of conjugated double bands. This study aimed to investigate whether lycopene inhibits the EtOH/POA-induced increase in ROS production, zymogen activation, and expression of the inflammatory cytokine IL-6 in EtOH/POA-stimulated pancreatic acinar AR42J cells. EtOH/POA increased the ROS levels, NADPH oxidase and NF-κB activities, zymogen activation, IL-6 expression, and mitochondrial dysfunction, which were inhibited by lycopene. The antioxidant N-acetylcysteine and NADPH oxidase 1 inhibitor ML171 suppressed the EtOH/POA-induced increases in ROS production, NF-κB activation, zymogen activation, and IL-6 expression. Therefore, lycopene inhibits EtOH/POA-induced mitochondrial dysfunction, zymogen activation, and IL-6 expression by suppressing NADPH oxidase-mediated ROS production in pancreatic acinar cells. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals)
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19 pages, 14599 KiB  
Article
5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction
by Sukkum Ngullie Chang, Se Ho Kim, Debasish Kumar Dey, Seon Min Park, Omaima Nasif, Vivek K. Bajpai, Sun Chul Kang, Jintae Lee and Jae Gyu Park
Int. J. Mol. Sci. 2021, 22(3), 1083; https://doi.org/10.3390/ijms22031083 - 22 Jan 2021
Cited by 36 | Viewed by 4119
Abstract
Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high [...] Read more.
Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl4). Subsequently, we investigated acute liver injury on BALB/c mice induced by CCl4 through the intraperitoneal injection of 1 mL/kg CCl4 and co-administration of 5-DN at (1 and 2 mg/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl4-induced elevated serum aminotransferase (AST)/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl4 treatment. Furthermore, the apoptotic response induced by CCl4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl4. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals)
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Review

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12 pages, 1143 KiB  
Review
The Anti-Inflammatory Properties of Licorice (Glycyrrhiza glabra)-Derived Compounds in Intestinal Disorders
by Camila dos Santos Leite, Gabriel Alves Bonafé, Juliana Carvalho Santos, Carlos Augusto Real Martinez, Manoela Marques Ortega and Marcelo Lima Ribeiro
Int. J. Mol. Sci. 2022, 23(8), 4121; https://doi.org/10.3390/ijms23084121 - 08 Apr 2022
Cited by 26 | Viewed by 4925
Abstract
Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC), are a significant source of morbidity and mortality worldwide. Epidemiological data have shown that IBD patients are at an increased risk for the development of CRC. IBD-associated cancer develops against a [...] Read more.
Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC), are a significant source of morbidity and mortality worldwide. Epidemiological data have shown that IBD patients are at an increased risk for the development of CRC. IBD-associated cancer develops against a background of chronic inflammation and oxidative stress, and their products contribute to cancer development and progression. Therefore, the discovery of novel drugs for the treatment of intestinal diseases is urgently needed. Licorice (Glycyrrhiza glabra) has been largely used for thousands of years in traditional Chinese medicine. Licorice and its derived compounds possess antiallergic, antibacterial, antiviral, anti-inflammatory, and antitumor effects. These pharmacological properties aid in the treatment of inflammatory diseases. In this review, we discuss the pharmacological potential of bioactive compounds derived from Licorice and addresses their anti-inflammatory and antioxidant properties. We also discuss how the mechanisms of action in these compounds can influence their effectiveness and lead to therapeutic effects on intestinal disorders. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals)
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