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Novel Therapeutic Targets and Potential Drugs for Inflammatory Disease

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Special Issue Information
Keywords
Published Papers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 11317

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Special Issue Editors

Dr. Xiaoyan Lu

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Guest Editor

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
Interests: inflammation; liver diseases; cancer; cardiovascular diseases; systems biology

Dr. Ligen Lin

E-Mail Website
Guest Editor

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China
Interests: natural products; diabetes; lipid metabolism; mitochondria; thermogenesis; insulin sensitivity; sirtuin; fatty liver
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammatory diseases, encompassing a wide variety of physical and mental disorders, are associated with more than 50% of global deaths. Representative diseases include COVID-19, stroke, allergy, asthma, hepatitis, cancer, diabetes mellitus, cardiovascular diseases, inflammatory bowel disease, autoimmune diseases, depression, and neurodegenerative diseases. Since inflammation determines the onset and progression of these diseases, understanding its mechanisms underlying the pathophysiological processes is a cornerstone in the discovering innovative therapeutic targets and drugs. Various exciting technologies and strategies have been employed to address the complexity and dynamics of inflammation, such as single-cell multi-omics and artificial intelligence, and many targets and biomarkers have emerged, enabling cell- and mechanism-specific interventions for these inflammatory diseases.

This Special Issue will publish experimental findings and review articles focused on novel therapeutic targets and potential drugs for inflammatory diseases. Topics of interest include but are not limited to, new molecular targets, natural- or synthetic-compound-based therapy, the therapeutic manipulation of specific cell types and their active products, and candidate biomarkers for diagnosis and treatment.

Dr. Xiaoyan Lu
Dr. Ligen Lin
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

molecular targets
bioactive compounds
biomarkers
cell-specific interventions
inflammatory mechanisms

Published Papers (6 papers)

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Research

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16 pages, 7408 KiB

Open AccessArticle

Paeonol Attenuates Atherosclerosis by Inhibiting Vascular Smooth Muscle Cells Senescence via SIRT1/P53/TRF2 Signaling Pathway

by Min Zhou, Xiaolin Ma, Menglong Gao, Hongfei Wu, Yarong Liu, Xiaoyan Shi and Min Dai

Molecules 2024, 29(1), 261; https://doi.org/10.3390/molecules29010261 - 04 Jan 2024

Viewed by 905

Abstract

Atherosclerosis is a chronic inflammatory disease leading to various vascular diseases. Vascular smooth muscle cell (VSMC) senescence promotes atherosclerotic inflammation and the formation of plaque necrosis core, in part through telomere damage mediated by a high-fat diet. Our previous research found that paeonol, a potential anti-inflammatory agent extracted from Cortex Moutan, could significantly improve VSMCs dysfunction. However, the impact of paeonol on the senescence of VSMCs remains unexplored. This study presents the protective effects of paeonol on VSMCs senescence, and its potential activity in inhibiting the progression of atherosclerosis in vivo and in vitro. Sirtuin 1 (SIRT1) is a nuclear deacetylase involved in cell proliferation, senescence, telomere damage, and inflammation. Here, SIRT1 was identified as a potential target of paeonol having anti-senescence and anti-atherosclerosis activity. Mechanistic studies revealed that paeonol binds directly to SIRT1 and then activates the SIRT1/P53/TRF2 pathway to inhibit VSMCs senescence. Our results suggested that SIRT1-mediated VSMCs senescence is a promising druggable target for atherosclerosis, and that pharmacological modulation of the SIRT1/P53/TRF2 signaling pathway by paeonol is of potential benefit for patients with atherosclerosis. Full article

(This article belongs to the Special Issue Novel Therapeutic Targets and Potential Drugs for Inflammatory Disease)

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15 pages, 4902 KiB

Open AccessArticle

Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB

by Ke-Gang Linghu, Guan-Ding Zhao, Dai-Yan Zhang, Shi-Hang Xiong, Guo-Ping Wu, Li-Yu Shen, Wen-Qing Cui, Tian Zhang, Yuan-Jia Hu, Bing Guo, Xiang-Chun Shen and Hua Yu

Molecules 2023, 28(10), 4241; https://doi.org/10.3390/molecules28104241 - 22 May 2023

Cited by 1 | Viewed by 1628

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease triggered by a cascading inflammatory response. Sigesbeckia Herba (SH) has long been utilized as a traditional remedy to alleviate symptoms associated with rheumatism. Our previous study found that leocarpinolide B (LB), a sesquiterpene lactone isolated from the whole plant of SH, possesses potent a anti-inflammatory effect on macrophages. This study was designed to evaluate the therapeutic effects of LB on RA, and further investigate the underlying mechanisms. In collagen type II-induced arthritic mice, LB was demonstrated to decrease the production of autoimmune antibodies in serum and inflammatory cytokines in the joint muscles and recover the decreased regulatory T lymphocytes in spleen. Moreover, LB significantly suppressed the inflammatory infiltration, formation of pannus and bone erosion in the paw joints. In vitro testing showed that LB inhibited the proliferation, migration, invasion, and secretion of inflammatory cytokines in IL-1β-induced human synovial SW982 cells. Network pharmacology and molecular docking suggested NF-κB p65 could be the potential target of LB on RA treatment, subsequent experimental investigation confirmed that LB directly interacted with NF-κB p65 and reduced the DNA binding activity of NF-κB in synovial cells. In conclusion, LB significantly attenuated the collagen type II-induced arthritis, which was at least involved in the inhibition of DNA binding activity of NF-κB through a direct binding to NF-κB p65. These findings suggest that LB could be a valuable lead compound for developing anti-RA drugs. Full article

(This article belongs to the Special Issue Novel Therapeutic Targets and Potential Drugs for Inflammatory Disease)

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13 pages, 4015 KiB

Open AccessArticle

Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3⁺ Treg in the Small Intestine

by Tamara Saksida, Verica Paunović, Ivan Koprivica, Dragica Mićanović, Bojan Jevtić, Natalija Jonić, Ivana Stojanović and Nada Pejnović

Molecules 2023, 28(8), 3366; https://doi.org/10.3390/molecules28083366 - 11 Apr 2023

Cited by 3 | Viewed by 1712

Abstract

Recent data indicate the link between the number and function of T regulatory cells (Treg) in the gut immune tissue and initiation and development of autoimmunity associated with type 1 diabetes (T1D). Since type 3 innate lymphoid cells (ILC3) in the small intestine are essential for maintaining FoxP3⁺ Treg and there are no data about the possible role of ILC3 in T1D pathogenesis, the aim of this study was to explore ILC3-Treg link during the development of T1D. Mature diabetic NOD mice had lower frequencies of IL-2-producing ILC3 and Treg in small intestine lamina propria (SILP) compared to prediabetic NOD mice. Similarly, in multiple low doses of streptozotocin (MLDS)-induced T1D in C57BL/6 mice, hyperglycemic mice exhibited lower numbers of ILC3, IL-2⁺ ILC3 and Treg in SILP compared to healthy controls. To boost T1D severity, mice were treated with broad-spectrum antibiotics (ABX) for 14 days prior to T1D induction by MLDS. The higher incidence of T1D in ABX-treated mice was associated with significantly lower frequencies of IL-2⁺ ILC3 and FoxP3⁺ Treg in SILP compared with mice without ABX treatment. The obtained findings show that the lower proportions of IL-2-expressing ILC3 and FoxP3⁺ Treg in SILP coincided with diabetes progression and severity. Full article

(This article belongs to the Special Issue Novel Therapeutic Targets and Potential Drugs for Inflammatory Disease)

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14 pages, 2586 KiB

Open AccessArticle

Taurocholic Acid and Glycocholic Acid Inhibit Inflammation and Activate Farnesoid X Receptor Expression in LPS-Stimulated Zebrafish and Macrophages

by Xutao Ge, Shaoze Huang, Can Ren and Lu Zhao

Molecules 2023, 28(5), 2005; https://doi.org/10.3390/molecules28052005 - 21 Feb 2023

Cited by 6 | Viewed by 2038

Abstract

A hyperactive immune response can be observed in patients with bacterial or viral infection, which may lead to the overproduction of proinflammatory cytokines, or “cytokine storm”, and a poor clinical outcome. Extensive research efforts have been devoted to the discovery of effective immune modulators, yet the therapeutic options are still very limited. Here, we focused on the clinically indicated anti-inflammatory natural product Calculus bovis and its related patent drug Babaodan to investigate the major active molecules in the medicinal mixture. Combined with high-resolution mass spectrometry, transgenic zebrafish-based phenotypic screening, and mouse macrophage models, taurochiolic acid (TCA) and glycoholic acid (GCA) were identified as two naturally derived anti-inflammatory agents with high efficacy and safety. Both bile acids significantly inhibited the lipopolysaccharide-induced macrophage recruitment and the secretion of proinflammatory cytokines/chemokines in in vivo and in vitro models. Further studies identified strongly increased expression of the farnesoid X receptor at both the mRNA and protein levels upon the administration of TCA or GCA, which may be essential for mediating the anti-inflammatory effects of the two bile acids. In conclusion, we identified TCA and GCA as two major anti-inflammatory compounds in Calculus bovis and Babaodan, which could be important quality markers for the future development of Calculus bovis, as well as promising lead compounds in the treatment of overactive immune responses. Full article

(This article belongs to the Special Issue Novel Therapeutic Targets and Potential Drugs for Inflammatory Disease)

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30 pages, 5226 KiB

Open AccessArticle

Effect of IL-27, Teriflunomide and Retinoic Acid and Their Combinations on CD4⁺ T Regulatory T Cells—An In Vitro Study

by Tomasz Maślanka

Molecules 2022, 27(23), 8471; https://doi.org/10.3390/molecules27238471 - 02 Dec 2022

Cited by 2 | Viewed by 1255

Abstract

The principal goal of the study was to verify the concept of pharmacological induction of Foxp3⁺CD25⁺CD4⁺ T regulatory (Treg) cells which will additionally be characterized by a highly suppressive phenotype, i.e., by extensive CD25 and CD39 expression and IL-10 and TGF-β production. Stimulated and unstimulated murine lymphocytes were exposed to IL-27, teriflunomide (TER), and all trans retinoic acid (ATRA) alone and to their combinations. The study demonstrated that: (a) IL-27 alone induced CD39 expression on Treg cells and the generation of Tr1 cells; (b) TER alone induced Foxp3-expressing CD4⁺ T cells and up-regulated density of CD25 on these cells; TER also induced the ability of Treg cells to TGF-β production; (c) ATRA alone induced CD39 expression on Treg cells. The experiments revealed a strong superadditive effect between IL-27 and ATRA with respect to increasing CD39 expression on Treg cells. Moreover, IL-27 and ATRA in combination, but not alone, induced the ability of Treg cells to IL-10 production. However, the combination of IL-27, TER, and ATRA did not induce the generation of Treg cell subset with all described above features. This was due to the fact that TER abolished all listed above desired effects induced by IL-27 alone, ATRA alone, and their combination. IL-27 alone, ATRA alone, and their combination affected TER-induced effects to a lesser extent. Therefore, it can be concluded that in the aspect of pharmacological induction of Treg cells with a highly suppressive phenotype, the triple combination treatment with TER, IL-27, and ATRA does not provide any benefits over TER alone or dual combination including IL-27 and ATRA. Full article

(This article belongs to the Special Issue Novel Therapeutic Targets and Potential Drugs for Inflammatory Disease)

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Review

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16 pages, 654 KiB

Open AccessReview

Progress and Prospects of Non-Canonical NF-κB Signaling Pathway in the Regulation of Liver Diseases

by Li Tao, Xiaomeng Ren, Wenhui Zhai and Zheng Chen

Molecules 2022, 27(13), 4275; https://doi.org/10.3390/molecules27134275 - 02 Jul 2022

Cited by 3 | Viewed by 2801

Abstract

Non-canonical nuclear factor kappa B (NF-κB) signaling pathway regulates many physiological and pathological processes, including liver homeostasis and diseases. Recent studies demonstrate that non-canonical NF-κB signaling pathway plays an essential role in hyperglycemia, non-alcoholic fatty liver disease, alcoholic liver disease, liver regeneration, liver injury, autoimmune liver disease, viral hepatitis, and hepatocellular carcinoma. Small-molecule inhibitors targeting to non-canonical NF-κB signaling pathway have been developed and shown promising results in the treatment of liver injuries. Here, the recent advances and future prospects in understanding the roles of the non-canonical NF-κB signaling pathways in the regulation of liver diseases are discussed. Full article

(This article belongs to the Special Issue Novel Therapeutic Targets and Potential Drugs for Inflammatory Disease)

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