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Natural Compounds for Inflammation and Anti-inflammatory Mechanism

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

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 19724

Special Issue Editors

Special Issue Information

Dear Colleagues,

Pain, heat, redness, and swelling (dolor, calor, rubor, tumor) are the classic manifestations of the inflammatory process. Abnormalities of the joints of the spine, associated muscles, tendons, ligaments and bone structural abnormalities can all result in pain and the need for neurosurgical consultations. In most cases, the genesis of pain is inflammatory, regardless of the etiology. With the elucidation of the role of inflammatory cytokines, there is now a clear understanding of the pathways by which many anti-inflammatory drugs can alleviate inflammation and relieve pain. Because of the significant side effect profiles of present steroidal and non-steroidal anti-inflammatory drug (NSAID) medications, there is a greater interest in natural compounds. Many of these natural compounds also work by inhibiting the inflammatory pathways in a similar manner as NSAIDs. In addition to the COX pathway, many natural compounds act to inhibit nuclear factor-kB (NF-kB) inflammatory pathways.

This Special Issue is open to both original research manuscripts and review articles focusing on natural inflammatory drugs and anti-inflammatory mechanisms. Importantly, the exact active ingredient and molecular formula of natural compounds must be reported in the submitted research manuscript, since papers describing the effects of mixed extraction from natural origin are not in the scope of the journal.   

Dr. Wonmin Ko
Dr. Dong-Sung Lee
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.

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Keywords

  • natural compounds
  • anti-inflammatory effects
  • anti-neuroinflammatory effects
  • macrophage
  • inflammation
  • cytokines

Published Papers (7 papers)

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Research

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11 pages, 1919 KiB  
Article
Anti-Inflammatory Effects Exerted by 14-Methoxyalternate C from Antarctic Fungal Strain Pleosporales sp. SF-7343 via the Regulation of NF-κB and JAK2/STAT3 in HaCaT Human Keratinocytes
by Linsha Dong, Thao Quyen Cao, Zhiming Liu, Nguyen Quoc Tuan, Youn-Chul Kim, Jae Hak Sohn, Joung Han Yim, Dong-Sung Lee and Hyuncheol Oh
Int. J. Mol. Sci. 2022, 23(23), 14642; https://doi.org/10.3390/ijms232314642 - 24 Nov 2022
Cited by 1 | Viewed by 1433
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a profound negative impact on patients’ quality of life. Four known secondary fungal metabolites were found in the chemical study of the Antarctic fungus Pleosporales sp. SF-7343, including 14-methoxyalternate C (1), [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a profound negative impact on patients’ quality of life. Four known secondary fungal metabolites were found in the chemical study of the Antarctic fungus Pleosporales sp. SF-7343, including 14-methoxyalternate C (1), 5′-methoxy-6-methyl-biphenyl-3,4,3′-triol (2), 3,8,10-trihydroxy-4-methoxy-6-methylbenzocoumarin (3), and alternariol monomethyl ether (4). Additionally, we identified the skin anti-inflammatory composition from the SF-7343 strain. Interleukin-8 and -6 Screening results showed that compound 1 inhibited IL-8 and IL-6 in tumor necrosis factor-α/interferon-γ stimulated HaCaT cells. Compound 1 showed inhibitory effects on MDC and RANTES. It also downregulated the expression of intercellular adhesion molecule-1 (ICAM-1) and upregulated the expression of involucrin. The results of the mechanistic study showed that compound 1 inhibited the nuclear translocation of nuclear factor-kappa B p65 and STAT3. In conclusion, this study demonstrates the potential of the Antarctic fungal strain SF-7343 as a bioactive resource to inhibit skin inflammation, such as AD. Full article
(This article belongs to the Special Issue Natural Compounds for Inflammation and Anti-inflammatory Mechanism)
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32 pages, 7122 KiB  
Article
Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis
by Rajveer Singh, Shivani Chandel, Arijit Ghosh, Tushar Matta, Anupam Gautam, Arka Bhattacharya, Srivalliputturu Sarath Babu, Soumi Sukla, Debasish Nag, Velayutham Ravichandiran, Syamal Roy and Dipanjan Ghosh
Int. J. Mol. Sci. 2022, 23(19), 11254; https://doi.org/10.3390/ijms231911254 - 24 Sep 2022
Cited by 6 | Viewed by 2962
Abstract
The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was [...] Read more.
The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was investigated. It was found that BGG pre-treatment showed a significant decrease in ROS, NO, superoxide, and pro-inflammatory cytokines (TNF-alpha, IL-4, IL-17, IL-1β, and IL-6) and increased reduced glutathione coupled with the restoration of mitochondrial membrane potential. Gene profiling and further validation by qPCR showed that BGG pre-treatment downregulated the LPS-induced expression of c-Fos, Fas, MMP-9, iNOS, COX-2, MyD88, TRIF, TRAF6, TRAM, c-JUN, and NF-κB. We observed that BGG pre-treatment reduced nuclear translocation of LPS-activated NF-κB and thus reduced the subsequent expressions of NLRP3 and IL-1β, indicating the ability of BGG to inhibit inflammasome formation. Molecular docking studies showed that BGG could bind at the active site of TLR4. Finally, in the LPS-driven sepsis mouse model, we showed that pre-treatment with BGG sustained toxic shock, as evident from their 100% survival. Our study clearly showed the therapeutic potential of BGG in toxic shock syndrome. Full article
(This article belongs to the Special Issue Natural Compounds for Inflammation and Anti-inflammatory Mechanism)
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20 pages, 4700 KiB  
Article
Baicalin Alleviates Short-Term Lincomycin-Induced Intestinal and Liver Injury and Inflammation in Infant Mice
by Shunfen Zhang, Ruqing Zhong, Shanlong Tang, Hui Han, Liang Chen and Hongfu Zhang
Int. J. Mol. Sci. 2022, 23(11), 6072; https://doi.org/10.3390/ijms23116072 - 28 May 2022
Cited by 6 | Viewed by 2485
Abstract
The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. It is, therefore, necessary to develop strategies [...] Read more.
The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. It is, therefore, necessary to develop strategies for reducing the adverse effects of antibiotics. Studies on the harm and rescue measures of antibiotics from the perspective of the gut–liver system are lacking. Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. However, baicalin administration attenuated the lincomycin-induced changes. Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. Bile acids can regulate intestinal immunity and strengthen hepatoenteric circulation. In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. Thus, baicalin can ameliorate antibiotic-induced injury and its associated complications such as liver disease. Full article
(This article belongs to the Special Issue Natural Compounds for Inflammation and Anti-inflammatory Mechanism)
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12 pages, 2633 KiB  
Article
Anti-Inflammatory Effects of Psoralen Derivatives on RAW264.7 Cells via Regulation of the NF-κB and MAPK Signaling Pathways
by Yeji Lee and Chang-Gu Hyun
Int. J. Mol. Sci. 2022, 23(10), 5813; https://doi.org/10.3390/ijms23105813 - 22 May 2022
Cited by 11 | Viewed by 2321
Abstract
Using repositioning to find new indications for existing functional substances has become a global target of research. The objective of this study is to investigate the anti-inflammatory potential of psoralen derivatives (5-hydroxypsoralen, 5-methoxypsoralen, 8-hydroxypsoralen, and 8-methoxypsoralen) in macrophages cells. The results indicated that [...] Read more.
Using repositioning to find new indications for existing functional substances has become a global target of research. The objective of this study is to investigate the anti-inflammatory potential of psoralen derivatives (5-hydroxypsoralen, 5-methoxypsoralen, 8-hydroxypsoralen, and 8-methoxypsoralen) in macrophages cells. The results indicated that most psoralen derivatives exhibited significantly inhibited prostaglandin E2 (PGE2) production, particularly for 8-hydroxypsoralen (xanthotoxol) in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. In addition, xanthotoxol treatment decreased the PGE2, IL-6, and IL-1β production caused by LPS stimulation in a concentration-dependent manner. Moreover, Western blot results showed that the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which activated with LPS treatment, were decreased by xanthotoxol treatment. Mechanistic studies revealed that xanthotoxol also suppressed LPS-stimulated phosphorylation of the inhibitor of κBα (IκBα), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) in RAW 264.7 cells. The Western blot assay results show that xanthotoxol suppresses LPS-induced p65 translocation from cytosol to the nucleus in RAW 264.7 cells. Moreover, we tested the potential application of xanthotoxol as a cosmetic material by performing human skin patch tests. In these tests, xanthotoxol did not induce any adverse reactions at a 100 μΜ concentration. These results demonstrate that xanthotoxol is a potential therapeutic agent for topical application that inhibits inflammation via the MAPK and NF-κB pathways. Full article
(This article belongs to the Special Issue Natural Compounds for Inflammation and Anti-inflammatory Mechanism)
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Review

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32 pages, 1117 KiB  
Review
The Anti-Inflammatory and Immunomodulatory Activities of Natural Products to Control Autoimmune Inflammation
by Kamal D. Moudgil and Shivaprasad H. Venkatesha
Int. J. Mol. Sci. 2023, 24(1), 95; https://doi.org/10.3390/ijms24010095 - 21 Dec 2022
Cited by 24 | Viewed by 4801
Abstract
Inflammation is an integral part of autoimmune diseases, which are caused by dysregulation of the immune system. This dysregulation involves an imbalance between pro-inflammatory versus anti-inflammatory mediators. These mediators include various cytokines and chemokines; defined subsets of T helper/T regulatory cells, M1/M2 macrophages, [...] Read more.
Inflammation is an integral part of autoimmune diseases, which are caused by dysregulation of the immune system. This dysregulation involves an imbalance between pro-inflammatory versus anti-inflammatory mediators. These mediators include various cytokines and chemokines; defined subsets of T helper/T regulatory cells, M1/M2 macrophages, activating/tolerogenic dendritic cells, and antibody-producing/regulatory B cells. Despite the availability of many anti-inflammatory/immunomodulatory drugs, the severe adverse reactions associated with their long-term use and often their high costs are impediments in effectively controlling the disease process. Accordingly, suitable alternatives are being sought for these conventional drugs. Natural products offer promising adjuncts/alternatives in this regard. The availability of specific compounds isolated from dietary/medicinal plant extracts have permitted rigorous studies on their disease-modulating activities and the mechanisms involved therein. Here, we describe the basic characteristics, mechanisms of action, and preventive/therapeutic applications of 5 well-characterized natural product compounds (Resveratrol, Curcumin, Boswellic acids, Epigallocatechin-3-gallate, and Triptolide). These compounds have been tested extensively in animal models of autoimmunity as well as in limited clinical trials in patients having the corresponding diseases. We have focused our description on predominantly T cell-mediated diseases, such as rheumatoid arthritis, multiple sclerosis, Type 1 diabetes, ulcerative colitis, and psoriasis. Full article
(This article belongs to the Special Issue Natural Compounds for Inflammation and Anti-inflammatory Mechanism)
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50 pages, 2216 KiB  
Review
Overview of Anti-Inflammatory and Anti-Nociceptive Effects of Polyphenols to Halt Osteoarthritis: From Preclinical Studies to New Clinical Insights
by Laura Gambari, Antonella Cellamare, Francesco Grassi, Brunella Grigolo, Alessandro Panciera, Alberto Ruffilli, Cesare Faldini and Giovanna Desando
Int. J. Mol. Sci. 2022, 23(24), 15861; https://doi.org/10.3390/ijms232415861 - 13 Dec 2022
Cited by 5 | Viewed by 2035
Abstract
Knee osteoarthritis (OA) is one of the most multifactorial joint disorders in adults. It is characterized by degenerative and inflammatory processes that are responsible for joint destruction, pain and stiffness. Despite therapeutic advances, the search for alternative strategies to target inflammation and pain [...] Read more.
Knee osteoarthritis (OA) is one of the most multifactorial joint disorders in adults. It is characterized by degenerative and inflammatory processes that are responsible for joint destruction, pain and stiffness. Despite therapeutic advances, the search for alternative strategies to target inflammation and pain is still very challenging. In this regard, there is a growing body of evidence for the role of several bioactive dietary molecules (BDMs) in targeting inflammation and pain, with promising clinical results. BDMs may be valuable non-pharmaceutical solutions to treat and prevent the evolution of early OA to more severe phenotypes, overcoming the side effects of anti-inflammatory drugs. Among BDMs, polyphenols (PPs) are widely studied due to their abundance in several plants, together with their benefits in halting inflammation and pain. Despite their biological relevance, there are still many questionable aspects (biosafety, bioavailability, etc.) that hinder their clinical application. This review highlights the mechanisms of action and biological targets modulated by PPs, summarizes the data on their anti-inflammatory and anti-nociceptive effects in different preclinical in vitro and in vivo models of OA and underlines the gaps in the knowledge. Furthermore, this work reports the preliminary promising results of clinical studies on OA patients treated with PPs and discusses new perspectives to accelerate the translation of PPs treatment into the clinics. Full article
(This article belongs to the Special Issue Natural Compounds for Inflammation and Anti-inflammatory Mechanism)
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27 pages, 1918 KiB  
Review
Anti-Inflammatory Mechanisms of Dietary Flavones: Tapping into Nature to Control Chronic Inflammation in Obesity and Cancer
by Anastasia Kariagina and Andrea I. Doseff
Int. J. Mol. Sci. 2022, 23(24), 15753; https://doi.org/10.3390/ijms232415753 - 12 Dec 2022
Cited by 9 | Viewed by 2600
Abstract
Flavones are natural phytochemicals broadly distributed in our diet. Their anti-inflammatory properties provide unique opportunities to control the innate immune system and inflammation. Here, we review the role of flavones in chronic inflammation with an emphasis on their impact on the molecular mechanisms [...] Read more.
Flavones are natural phytochemicals broadly distributed in our diet. Their anti-inflammatory properties provide unique opportunities to control the innate immune system and inflammation. Here, we review the role of flavones in chronic inflammation with an emphasis on their impact on the molecular mechanisms underlying inflammatory diseases including obesity and cancer. Flavones can influence the innate immune cell repertoire restoring the immune landscape. Flavones impinge on NF-κB, STAT, COX-2, or NLRP3 inflammasome pathways reestablishing immune homeostasis. Devoid of adverse side effects, flavones could present alternative opportunities for the treatment and prevention of chronic inflammation that contributes to obesity and cancer. Full article
(This article belongs to the Special Issue Natural Compounds for Inflammation and Anti-inflammatory Mechanism)
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