Anti-Inflammatory Mechanisms of Fucoidans to Treat Inflammatory Diseases: A Review

Fucoidans are sulfated heteropolysaccharides found in the cell walls of brown seaweeds (Phaeophyceae) and in some marine invertebrates. Generally, fucoidans are composed of significant amounts of L-fucose and sulfate groups, and lesser amounts of arabinose, galactose, glucose, glucuronic acid, mannose, rhamnose, and xylose. In recent years, fucoidans isolated from brown seaweeds have gained considerable attention owing to their promising bioactive properties such as antioxidant, immunomodulatory, anti-inflammatory, antiobesity, antidiabetic, and anticancer properties. Inflammation is a complex immune response that protects the organs from infection and tissue injury. While controlled inflammatory responses are beneficial to the host, leading to the removal of immunostimulants from the host tissues and restoration of structural and physiological functions in the host tissues, chronic inflammatory responses are often associated with the pathogenesis of tumor development, arthritis, cardiovascular diseases, diabetes, obesity, and neurodegenerative diseases. In this review, the authors mainly discuss the studies since 2016 that have reported anti-inflammatory properties of fucoidans isolated from various brown seaweeds, and their potential as a novel functional material for the treatment of inflammatory diseases.

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Cell-extrinsic autophagy in mature adipocytes regulates anti-inflammatory response to intestinal tissue injury through lipid mobilization

10.1101/2021.10.25.465200 ◽

2021 ◽

Author(s):

Felix Clemens Richter ◽

Matthias Friedrich ◽

Mathilde Pohin ◽

Ghada Alsaleh ◽

Irina Guschina ◽

...

Keyword(s):

Adipose Tissue ◽

Intestinal Inflammation ◽

Inflammatory Responses ◽

Tissue Injury ◽

Inflammatory Diseases ◽

Protective Effects ◽

Adipose Tissue Macrophages ◽

Anti Inflammatory ◽

Major Nutrients

Autophagy is a critical cellular recycling pathway which is genetically linked to the development of intestinal inflammation in humans. Inflammation drives adipose tissue breakdown and provision of major nutrients such as free fatty acids (FFA). However, the effect of autophagy-mediated FFA release by adipocytes in immune-mediated inflammatory diseases remains unexplored. In a mouse model of intestinal inflammation, we found that visceral adipocytes upregulate autophagy at peak inflammation. Adipocyte-specific loss of the key autophagy gene Atg7 (Atg7Ad) resulted in the exacerbation of intestinal inflammation. TNFα-induced lipolysis was impaired in Atg7-deficient adipocytes leading to the reduced availability of several FFA species, and decreased expression of the FFA transporter CD36 on adipose tissue macrophages (ATMs). Visceral adipose tissues from Atg7Ad mice released less IL-10 resulting in lower levels of circulating IL-10 in colitis. ATMs present the main source of adipose tissue-derived IL-10 during colitis. In vitro assays confirmed that FFA restriction from macrophages reduced CD36 expression and diminished IL-10 production. Taken together, our study demonstrates that autophagy-mediated FFA release from adipocytes directs anti-inflammatory responses in ATMs, which in turn conveys protective effects for distant intestinal inflammation.

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Anti-Inflammatory and Anticancer Properties of Bioactive Compounds from Sesamum indicum L.—A Review

Molecules ◽

10.3390/molecules24244426 ◽

2019 ◽

Vol 24 (24) ◽

pp. 4426 ◽

Cited By ~ 8

Author(s):

Ming-Shun Wu ◽

Levent Bless B. Aquino ◽

Marjette Ylreb U. Barbaza ◽

Chieh-Lun Hsieh ◽

Kathlia A. De Castro-Cruz ◽

...

Keyword(s):

Chronic Diseases ◽

Inflammatory Diseases ◽

Antioxidant Properties ◽

Sesamum Indicum ◽

The Body ◽

Anticancer Activities ◽

Anticancer Properties ◽

Pharmacological Significance ◽

Anti Inflammatory ◽

Natural Medicines

The use of foodstuff as natural medicines has already been established through studies demonstrating the pharmacological activities that they exhibit. Knowing the nutritional and pharmacological significance of foods enables the understanding of their role against several diseases. Among the foods that can potentially be considered as medicine, is sesame or Sesamum indicum L., which is part of the Pedaliaceae family and is composed of its lignans such as sesamin, sesamol, sesaminol and sesamolin. Its lignans have been widely studied and are known to possess antiaging, anticancer, antidiabetes, anti-inflammatory and antioxidant properties. Modern chronic diseases, which can transform into clinical diseases, are potential targets of these lignans. The prime example of chronic diseases is rheumatic inflammatory diseases, which affect the support structures and the organs of the body and can also develop into malignancies. In line with this, studies emphasizing the anti-inflammatory and anticancer activities of sesame have been discussed in this review.

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Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7 Macrophages

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/7383104 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 4

Author(s):

Hee-Soo Han ◽

Eungyeong Jang ◽

Ji-Sun Shin ◽

Kyung-Soo Inn ◽

Jang-Hoon Lee ◽

...

Keyword(s):

Signaling Pathway ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Molecular Data ◽

Mrna Levels ◽

Protein Levels ◽

Stat3 Phosphorylation ◽

Stat Signaling ◽

Cox 2 ◽

Anti Inflammatory

Medicinal plants have been used as alternative therapeutic tools to alleviate inflammatory diseases. The objective of this study was to evaluate anti-inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3–11 herbs in LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS-induced NO, PGE2, TNF-α, and IL-6 production among those three herbal formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2 at protein levels and expression of iNOS, COX-2, TNF-α, and IL-6 at mRNA levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT signaling cascade without affecting NF-κB or AP-1 activation. In ear inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear tissues. Taken together, our findings suggest that KCT-01 can downregulate the expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway under inflammatory conditions. This study provides useful data for further exploration and application of KCT-01 as a potential anti-inflammatory medicine.

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p38/AP-1 Pathway in Lipopolysaccharide-Induced Inflammatory Responses Is Negatively Modulated by Electrical Stimulation

Mediators of Inflammation ◽

10.1155/2013/183042 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Deok Jeong ◽

Jaehwi Lee ◽

Young-Su Yi ◽

Yanyan Yang ◽

Kyoung Won Kim ◽

...

Keyword(s):

Electrical Stimulation ◽

Inflammatory Response ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Physiological Role ◽

Peritoneal Macrophages ◽

Cellular Level ◽

Transcriptional Level ◽

Weak Current ◽

Anti Inflammatory

Electrical stimulation with a weak current has been demonstrated to modulate various cellular and physiological responses, including the differentiation of mesenchymal stem cells and acute or chronic physical pain. Thus, a variety of investigations regarding the physiological role of nano- or microlevel currents at the cellular level are actively proceeding in the field of alternative medicine. In this study, we focused on the anti-inflammatory activity of aluminum-copper patches (ACPs) under macrophage-mediated inflammatory conditions. ACPs generated nanolevel currents ranging from 30 to 55 nA in solution conditions. Interestingly, the nanocurrent-generating aluminum-copper patches (NGACPs) were able to suppress both lipopolysaccharide-(LPS-) and pam3CSK-induced inflammatory responses such as NO and PGE2production in both RAW264.7 cells and peritoneal macrophages at the transcriptional level. Through immunoblotting and immunoprecipitation analyses, we found that p38/AP-1 could be the major inhibitory pathway in the NGACP-mediated anti-inflammatory response. Indeed, inhibition of p38 by SB203580 showed similar inhibitory activity of the production of TNF-αand PGE2and the expression of TNF-αand COX-2 mRNA. These results suggest that ACP-induced nanocurrents alter signal transduction pathways that are involved in the inflammatory response and could therefore be utilized in the treatment of various inflammatory diseases such as arthritis and colitis.

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DNA damage independent inhibition of NF-κB transcription by anthracyclines

10.1101/2020.04.27.065003 ◽

2020 ◽

Author(s):

Angelo Chora ◽

Dora Pedroso ◽

Nadja Pejanovic ◽

Eleni Kyriakou ◽

Henrique Colaço ◽

...

Keyword(s):

Dna Damage ◽

Transcription Factors ◽

Binding Sites ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Anticancer Properties ◽

Dna Binding Sites ◽

Immune Mediated ◽

Life Threatening ◽

Molecular Patterns

AbstractTranscriptional programs leading to induction of a large number of genes can be rapidly initiated by the activation of only few selected transcription factors. Upon stimulation of macrophages with microbial-associated molecular patterns (MAMPs), the activation of the nuclear factor kappa B (NF-κB) family of transcription factors triggers inflammatory responses that, left uncontrolled, can lead to excessive inflammation with life-threatening consequences for the host. Here we identify and characterize a novel effect of Anthracyclines, a class of drugs currently used as potent anticancer drugs, in the regulation of NF-κB transcriptional activity in BMDMs, in addition to the previously reported DNA damage and histone eviction. Anthracyclines, including Doxorubicin, Daunorubicin and Epirubicin, disturb the complexes formed between the NF-κB subunit RelA and its DNA binding sites, to limit NF-κB-dependent gene transcription during inflammatory responses, including of pivotal pro-inflammatory mediators such as TNF. We observed that suppression of inflammation can also be mediated by Aclarubicin, Doxorubicinone and the newly developed Dimethyl-doxorubicin, which share anticancer properties with the other Anthracyclines, but do not induce DNA damage in the tested concentrations. This novel mechanism of action of Anthracyclines, contributing to the reduction of inflammation, is thus independent of the activation of DNA damage responses and may be relevant for the development of novel strategies targeting immune-mediated inflammatory diseases.

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Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

Molecules ◽

10.3390/molecules25235717 ◽

2020 ◽

Vol 25 (23) ◽

pp. 5717 ◽

Cited By ~ 1

Author(s):

Jung-Yeon Kim ◽

Jaechan Leem ◽

Kwan-Kyu Park

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Immune Cell ◽

Inflammatory Responses ◽

Tissue Injury ◽

Therapeutic Option ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Kidney Injury ◽

Heme Oxygenase 1 ◽

Anti Inflammatory

Sepsis is the major cause of acute kidney injury (AKI) in severely ill patients, but only limited therapeutic options are available. During sepsis, lipopolysaccharide (LPS), an endotoxin derived from bacteria, activates signaling cascades involved in inflammatory responses and tissue injury. Apamin is a component of bee venom and has been shown to exert antioxidative, antiapoptotic, and anti-inflammatory activities. However, the effect of apamin on LPS-induced AKI has not been elucidated. Here, we show that apamin treatment significantly ameliorated renal dysfunction and histological injury, especially tubular injury, in LPS-injected mice. Apamin also suppressed LPS-induced oxidative stress through modulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and heme oxygenase-1. Moreover, tubular cell apoptosis with caspase-3 activation in LPS-injected mice was significantly attenuated by apamin. Apamin also inhibited cytokine production and immune cell accumulation, suppressed toll-like receptor 4 pathway, and downregulated vascular adhesion molecules. Taken together, these results suggest that apamin ameliorates LPS-induced renal injury through inhibiting oxidative stress, apoptosis of tubular epithelial cells, and inflammation. Apamin might be a potential therapeutic option for septic AKI.

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Effect of Kramecyne on the Inflammatory Response in Lipopolysaccharide-Stimulated Peritoneal Macrophages

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/762020 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

E. Sánchez-Miranda ◽

J. Lemus-Bautista ◽

S. Pérez ◽

J. Pérez-Ramos

Keyword(s):

Nitric Oxide ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Peritoneal Macrophages ◽

Anti Inflammatory ◽

Oxide Synthase ◽

North And South America ◽

North And South ◽

Mouse Peritoneal Macrophages ◽

Necrosis Factor

Kramecyne is a new peroxide, it was isolated fromKrameria cytisoides, methanol extract, and this plant was mostly found in North and South America. This compound showed potent anti-inflammatory activity; however, the mechanisms by which this compound exerts its anti-inflammatory effect are not well understood. In this study, we examined the effects of kramecyne on inflammatory responses in mouse lipopolysaccharide- (LPS-) induced peritoneal macrophages. Our findings indicate that kramecyne inhibits LPS-induced production of tumor necrosis factor (TNF-α) and interleukin- (IL-) 6. During the inflammatory process, levels of cyclooxygenase- (COX-) 2, nitric oxide synthase (iNOS), and nitric oxide (NO) increased in mouse peritoneal macrophages; however, kramecyne suppressed them significantly. These results provide novel insights into the anti-inflammatory actions and support its potential use in the treatment of inflammatory diseases.

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Regulation of Notch 1 signaling in THP-1 cells enhances M2 macrophage differentiation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00896.2013 ◽

2014 ◽

Vol 307 (11) ◽

pp. H1634-H1642 ◽

Cited By ~ 24

Author(s):

Reetu D. Singla ◽

Jing Wang ◽

Dinender K. Singla

Keyword(s):

Notch Signaling ◽

Proinflammatory Cytokine ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Macrophage Polarization ◽

Cellular Stress ◽

Culture Conditions ◽

M2 Macrophage ◽

Macrophage Differentiation ◽

Anti Inflammatory

Macrophage polarization is emerging as an important area of research for the development of novel therapeutics to treat inflammatory diseases. Within the current study, the role of Notch1R in macrophage differentiation was investigated as well as downstream effects in THP-1 monocytes cultured in “inflammation mimicry” media. Interference of Notch signaling was achieved using either the pharmaceutical inhibitor DAPT or Notch1R small interfering RNA (siRNA), and Notch1R expression, macrophage phenotypes, and anti- and proinflammatory cytokine expression were evaluated. Data presented show that Notch1R expression on M1 macrophages as well as M1 macrophage differentiation is significantly elevated during cellular stress ( P < 0.05). However, under identical culture conditions, interference to Notch signaling via Notch1R inhibition mitigated these results as well as promoted M2 macrophage differentiation. Moreover, when subjected to cellular stress, macrophage secretion of proinflammatory cytokines was significantly heightened ( P < 0.05). Importantly, Notch1R inhibition not only diminished proinflammatory cytokine secretion but also enhanced anti-inflammatory protein release ( P < 0.05). Our data suggest that Notch1R plays a pivotal role in M1 macrophage differentiation and heightened inflammatory responses. Therefore, we conclude that inhibition of Notch1R and subsequent downstream signaling enhances monocyte to M2 polarized macrophage outcomes and promotes anti-inflammatory mediation during cellular stress.

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Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.620984 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yufei Xie ◽

Annemarie H. Meijer ◽

Marcel J. M. Schaaf

Keyword(s):

Immune System ◽

Inflammatory Response ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Critical Role ◽

Model Systems ◽

Trinitrobenzene Sulfonic Acid ◽

Inflammatory Drugs ◽

Anti Inflammatory

Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responses in vivo at the early life stages. This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (hai1a) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (cdipt) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.

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PPARγin Bacterial Infections: A Friend or Foe?

PPAR Research ◽

10.1155/2016/7963540 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Aravind T. Reddy ◽

Sowmya P. Lakshmi ◽

Raju C. Reddy

Keyword(s):

Bacterial Infections ◽

Inflammatory Responses ◽

Tissue Injury ◽

Antibacterial Properties ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Therapeutic Modalities ◽

Anti Inflammatory ◽

And Function

Peroxisome proliferator-activated receptorγ(PPARγ) is now recognized as an important modulator of leukocyte inflammatory responses and function. Its immunoregulatory function has been studied in a variety of contexts, including bacterial infections of the lungs and central nervous system, sepsis, and conditions such as chronic granulomatous disease. Although it is generally believed that PPARγactivation is beneficial for the host during bacterial infections via its anti-inflammatory and antibacterial properties, PPARγagonists have also been shown to dampen the host immune response and in some cases exacerbate infection by promoting leukocyte apoptosis and interfering with leukocyte migration and infiltration. In this review we discuss the role of PPARγand its activation during bacterial infections, with focus on the potential of PPARγagonists and perhaps antagonists as novel therapeutic modalities. We conclude that adjustment in the dosage and timing of PPARγagonist administration, based on the competence of host antimicrobial defenses and the extent of inflammatory response and tissue injury, is critical for achieving the essential balance between pro- and anti-inflammatory effects on the immune system.

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