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Molecular Mechanism of Anti-inflammatory Actions of Natural Components

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 39883

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Special Issue Editors

Prof. Dr. Jae Youl Cho

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Department of Integrative Biotechnology, Director, Institute of Biomolecule Control, Sungkyunkwan University, 2066 Seobu-ro, Suwon 16419, Republic of Korea
Interests: inflammation; cancer; signal transduction pathway; protein methylation; natural products; flavonoids; saponins; innate immunity; gastritis; colitis; hepatitis, arthritis, atopic dermatitis
Special Issues, Collections and Topics in MDPI journals

Dr. Hassan Hosseinzadeh

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School of Health and Society, Faculty of the Arts, Social Sciences and Humanities, University of Wollongong, Wollongong, NSW 2522, Australia
Interests: chronic diseases; digital health; primary care and health promotion
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It has been well documented that natural components could play critical roles in modern anti-inflammatory drug development. Inflammatory substances are usually divided into two main categories: pro- and anti-inflammatory mediators. Nevertheless, some mediators such as interleukin (IL)-12 possess both pro and anti-inflammatory properties. Among the inflammatory mediators and cellular pathways that have been extensively studied in association with human pathological conditions are cytokines , chemokines, eicosanoids and the potent inflammation-modulating transcription factor nuclear factor κ B. Natural components have been reported to exert anti-inflammatory activity both in vitro and in vivo conditions, and they have an impact on the pro-inflammatory gene expression, such as cyclooxygenase-2, nitric oxide synthase, pivotal cytokine etc. In this Special Issue, we will discuss the natural components, their roles in inflammation, and the therapeutic potential of these agents. The papers published here will surely contribute to proposing new additional insights into the anti-inflammatory mechanism of natural components. Importantly, the exact active ingredient of plant extract must be reported in the submitted research manuscript, since papers describing effects of mixed extraction from plants will not be accepted.

Prof. Dr. Jae Cho
Dr. Hassan Hosseinzadeh
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

Acute inflammation
Chronic inflammation
Macrophages
Signal transduction
Protein kinases
Pro-inflammatory cytokines

Published Papers (14 papers)

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Research

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14 pages, 1797 KiB

Open AccessArticle

HPLC Analysis of Polyphenols Derived from Hungarian Aszú from Tokaj Wine Region and Its Effect on Inflammation in an In Vitro Model System of Endothelial Cells

by Arnold Markovics, László Csige, Erzsébet Szőllősi, Hajnalka Matyi, Andrea Diána Lukács, Nóra Réka Perez, Zsófia Réka Bacsó, László Stündl, Judit Remenyik and Attila Biró

Int. J. Mol. Sci. 2023, 24(7), 6124; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076124 - 24 Mar 2023

Viewed by 1183

Abstract

Many studies have been published in recent years regarding the fact that moderate wine consumption, as a part of a balanced diet can have a beneficial effect on human health. The biologically active components of wine continue to be the subject of intense research today. In this study, the bioactive molecules of Hungarian aszú from the Tokaj wine region were analyzed using high-performance liquid chromatography (HPLC) and investigated in an in vitro model system of endothelial cells induced by bacterial-derived lipopolysaccharide. The HPLC measurements were performed on a reversed phased column with gradient elution. The non-cytotoxic concentration of the active substance was determined based on 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT)-, apoptosis, and necrosis assays. The antioxidant effect of the extract was determined by evaluating its ability to eliminate ROS. The expressions of the interleukin-(IL)1α, IL1-β, IL-6, and IL-8 pro-inflammatory cytokines and nitric oxide synthase (eNOS) at the mRNA level were evaluated using a quantitative polymerase chain reaction (qPCR). We found that the lipopolysaccharides (LPS)-induced increases in the expressions of the investigated cytokines were significantly suppressed by Hungarian aszú extract, excluding IL-6. In our experimental setup, our treatment had a positive effect on the eNOS expression, which was impaired as a result of the inflammatory manipulation. In our experimental model, the Hungarian aszú extract decreased the LPS-induced increases in the expression of the investigated cytokines and eNOS at the mRNA level, which presumably had a positive effect on the endothelial dysfunction caused by inflammation due to its strong antioxidant and anti-inflammatory effects. Collectively, this research contributes to a more thorough understanding of the bioactive molecules of aszú from the Tokaj wine region. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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25 pages, 9473 KiB

Open AccessArticle

β-Caryophyllene Acts as a Ferroptosis Inhibitor to Ameliorate Experimental Colitis

by Yan-Ting Wu, Li-Shan Zhong, Chen Huang, Yu-Ying Guo, Fu-Jun Jin, Yu-Ze Hu, Zi-Bo Zhao, Zhe Ren and Yi-Fei Wang

Int. J. Mol. Sci. 2022, 23(24), 16055; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232416055 - 16 Dec 2022

Cited by 5 | Viewed by 2299

Abstract

Macrophage infiltration is one of the main pathological features of ulcerative colitis (UC) and ferroptosis is a type of nonapoptotic cell death, connecting oxidative stress and inflammation. However, whether ferroptosis occurs in the colon macrophages of UC mice and whether targeting macrophage ferroptosis is an effective approach for UC treatment remain unclear. The present study revealed that macrophage lipid peroxidation was observed in the colon of UC mice. Subsequently, we screened several main components of essential oil from Artemisia argyi and found that β-caryophyllene (BCP) had a good inhibitory effect on macrophage lipid peroxidation. Additionally, ferroptotic macrophages were found to increase the mRNA expression of tumor necrosis factor alpha (Tnf-α) and prostaglandin-endoperoxide synthase 2 (Ptgs2), while BCP can reverse the effects of inflammation activated by ferroptosis. Further molecular mechanism studies revealed that BCP activated the type 2 cannabinoid receptor (CB2R) to inhibit macrophage ferroptosis and its induced inflammatory response both in vivo and in vitro. Taken together, BCP potentially ameliorated experimental colitis inflammation by inhibiting macrophage ferroptosis. These results revealed that macrophage ferroptosis is a potential therapeutic target for UC and identified a novel mechanism of BCP in ameliorating experimental colitis. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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12 pages, 1864 KiB

Open AccessArticle

2-O-β-d-Glucopyranosyl-4,6-dihydroxybenzaldehyde Isolated from Morus alba (Mulberry) Fruits Suppresses Damage by Regulating Oxidative and Inflammatory Responses in TNF-α-Induced Human Dermal Fibroblasts

by Kang Sub Kim, Yea Jung Choi, Dae Sik Jang and Sullim Lee

Int. J. Mol. Sci. 2022, 23(23), 14802; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314802 - 26 Nov 2022

Cited by 4 | Viewed by 1289

Abstract

Human skin is composed of three layers, of which the dermis is composed of an extracellular matrix (ECM) comprising collagen, elastin, and other proteins. These proteins are reduced due to skin aging caused by intrinsic and extrinsic factors. Among various internal and external factors related to aging, ultraviolet (UV) radiation is the main cause of photoaging of the skin. UV radiation stimulates DNA damage, reactive oxygen species (ROS) generation, and pro-inflammatory cytokine production such as tumor necrosis factor-alpha (TNF-α), and promotes ECM degradation. Stimulation with ROS and TNF-α upregulates mitogen-activated protein kinases (MAPKs), nuclear factor kappa B (NF-κB), and activator protein 1 (AP-1) transcription factors that induce the expression of the collagenase matrix metalloproteinase-1 (MMP-1). Moreover, TNF-α induces intracellular ROS production and several molecular pathways. Skin aging progresses through various processes and can be prevented through ROS generation and TNF-α inhibition. In our previous study, 2-O-β-d-glucopyranosyl-4,6-dihydroxybenzaldehyde (GDHBA) was isolated from the Morus alba (mulberry) fruits and its inhibitory effect on MMP-1 secretion was revealed. In this study, we focused on the effect of GDHBA on TNF-α-induced human dermal fibroblasts (HDFs). GDHBA (50 μM) inhibited ROS generation (18.8%) and decreased NO (58.4%) and PGE₂ levels (53.8%), significantly. Moreover, it decreased MMP-1 secretion (55.3%) and increased pro-collagen type I secretion (207.7%). GDHBA (50 μM) decreased the expression of different MAPKs as per western blotting; p-38: 35.9%; ERK: 47.9%; JNK: 49.5%; c-Jun: 32.1%; NF-κB: 55.9%; and cyclooxygenase-2 (COX-2): 31%. This study elucidated a novel role of GDHBA in protecting against skin inflammation and damage through external stimuli, such as UV radiation. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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16 pages, 1904 KiB

Open AccessArticle

Trifuhalol A Suppresses Allergic Inflammation through Dual Inhibition of TAK1 and MK2 Mediated by IgE and IL-33

by Sim-Kyu Bong, No-June Park, Sang Heon Lee, Jin Woo Lee, Aaron Taehwan Kim, Xiaoyong Liu, Sang Moo Kim, Min Hye Yang, Yong Kee Kim and Su-Nam Kim

Int. J. Mol. Sci. 2022, 23(17), 10163; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231710163 - 05 Sep 2022

Cited by 6 | Viewed by 1751

Abstract

The activation and degranulation of immune cells play a pivotal role in allergic inflammation, a pathological condition that includes anaphylaxis, pruritus, and allergic march-related diseases. In this study, trifuhalol A, a phlorotannin isolated from Agarum cribrosum, inhibited the degranulation of immune cells and the biosynthesis of IL-33 and IgE in differentiated B cells and keratinocytes, respectively. Additionally, trifuhalol A suppressed the IL-33 and IgE-mediated activation of RBL-2H3 cells through the regulation of the TAK1 and MK2 pathways. Hence, the effect of trifuhalol A on allergic inflammation was evaluated using a Compound 48/80-induced systemic anaphylaxis mouse model and a house dust mite (HDM)-induced atopic dermatitis (AD) mouse model. Trifuhalol A alleviated anaphylactic death and pruritus, which appeared as an early-phase reaction to allergic inflammation in the Compound 48/80-induced systemic anaphylaxis model. In addition, trifuhalol A improved symptoms such as itching, edema, erythema, and hyperkeratinization in HDM-induced AD mice as a late-phase reaction. Moreover, the expression of IL-33 and thymic stromal lymphopoietin, inflammatory cytokines secreted from activated keratinocytes, was significantly reduced by trifuhalol A administration, resulting in the reduced infiltration of immune cells into the skin and a reduction in the blood levels of IgE and IL-4. In summarizing the above results, these results confirm that trifuhalol A is a potential therapeutic candidate for the regulation of allergic inflammation. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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16 pages, 4065 KiB

Open AccessArticle

Lobelia chinensis Extract and Its Active Compound, Diosmetin, Improve Atopic Dermatitis by Reinforcing Skin Barrier Function through SPINK5/LEKTI Regulation

by No-June Park, Beom-Geun Jo, Sim-Kyu Bong, Sang-a Park, Sullim Lee, Yong Kee Kim, Min Hye Yang and Su-Nam Kim

Int. J. Mol. Sci. 2022, 23(15), 8687; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158687 - 04 Aug 2022

Cited by 1 | Viewed by 2070

Abstract

The skin acts as a mechanical barrier that protects the body from the exterior environment, and skin barrier function is attributed to the stratum corneum (SC), which is composed of keratinocytes and skin lipids. Skin barrier homeostasis is maintained by a delicate balance between the differentiation and exfoliation of keratinocytes, and keratinocyte desquamation is regulated by members of the serine protease kalikrein (KLK) family and their endogenous inhibitor SPINK5/LEKTI (serine protease inhibitor Kazal type 5/lympho-epithelial Kazal-type-related inhibitor). Furthermore, SPINK5/LEKTI deficiency is involved in impaired skin barrier function caused by KLK over-activation. We sought to determine whether increased SPINK5/LEKTI expression ameliorates atopic dermatitis (AD) by strengthening skin barrier function using the ethanol extract of Lobelia chinensis (LCE) and its active compound, diosmetin, by treating human keratinocytes with UVB and using a DNCB-induced murine model of atopic dermatitis. LCE or diosmetin dose-dependently increased the transcriptional activation of SPINK5 promoter and prevented DNCB-induced skin barrier damage by modulating events downstream of SPINK5, that is, KLK, PAR2 (protease activated receptor 2), and TSLP (thymic stromal lymphopoietin). LCE or diosmetin normalized immune response in DNCB treated SKH-1 hairless mice as determined by reductions in serum immunoglobulin E and interleukin-4 levels and numbers of lesion-infiltrating mast cells. Our results suggest that LCE and diosmetin are good candidates for the treatment of skin barrier-disrupting diseases such as Netherton syndrome or AD, and that they do so by regulating SPINK5/LEKTI. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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11 pages, 2029 KiB

Open AccessArticle

Cassiaside C Inhibits M1 Polarization of Macrophages by Downregulating Glycolysis

by Ye Jin Kim, Sungwoo Lee, Jonghwa Jin, Hyein Woo, Yeon-Kyung Choi and Keun-Gyu Park

Int. J. Mol. Sci. 2022, 23(3), 1696; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031696 - 01 Feb 2022

Cited by 7 | Viewed by 2548

Abstract

Classically activated M1 macrophages reprogram their metabolism towards enhanced glycolysis to obtain energy and produce pro-inflammatory cytokines after activation by mammalian target of rapamycin complex 1 (mTORC1) and hypoxia-inducible factor (HIF)-1α. Thus, a strategy that constrains M1 polarization of macrophages via downregulation of glycolysis is essential for treating chronic inflammatory diseases. Cassiae semen has pharmacological activity against various inflammatory diseases. However, it is unclear whether specific compounds within Cassia seeds affect M1 polarization of macrophages. Here, we investigated whether Cassiaside C napthopyrone from Cassiae semen inhibits M1 polarization by downregulating glycolysis. We found that Cassiaside C reduced expression of inducible nitric oxide synthase and cyclooxygenase-2 and the phosphorylation of nuclear factor kappa B, all of which are upregulated in lipopolysaccharide (LPS)/interferon (IFN)-γ-treated Raw264.7 cells and peritoneal macrophages. Moreover, Cassiaside C-treated macrophages showed marked suppression of LPS/IFN-γ-induced HIF-1α, pyruvate dehydrogenase kinase 1, and lactate dehydrogenase A expression, along with downregulation of the phosphoinositide 3-kinases (PI3K)/AKT/mTORC1 signaling pathway. Consequently, Cassiaside C attenuated enhanced glycolysis and lactate production, but rescued diminished oxidative phosphorylation, in M1 polarized macrophages. Thus, Cassiaside C dampens M1 polarization of macrophages by downregulating glycolysis, which could be exploited as a therapeutic strategy for chronic inflammatory conditions. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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20 pages, 3205 KiB

Open AccessArticle

Anti-Inflammatory, Antioxidant, Moisturizing, and Antimelanogenesis Effects of Quercetin 3-O-β-D-Glucuronide in Human Keratinocytes and Melanoma Cells via Activation of NF-κB and AP-1 Pathways

by Anh Thu Ha, Laily Rahmawati, Long You, Mohammad Amjad Hossain, Jong-Hoon Kim and Jae Youl Cho

Int. J. Mol. Sci. 2022, 23(1), 433; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010433 - 31 Dec 2021

Cited by 32 | Viewed by 4111

Abstract

Quercetin 3-O-β-D-glucuronide (Q-3-G), the glucuronide conjugate of quercetin, has been reported as having anti-inflammatory properties in the lipopolysaccharide-stimulated macrophages, as well as anticancer and antioxidant properties. Unlike quercetin, which has been extensively described to possess a wide range of pharmacological activities including skin protective effects, the pharmacological benefits and mechanisms Q-3-G in the skin remained to be elucidated. This study focused on characterizing the skin protective properties, including anti-inflammatory and antioxidant properties, of Q-3-G against UVB-induced or H₂O₂-induced oxidative stress, the hydration effects, and antimelanogenesis activities using human keratinocytes (HaCaT) and melanoma (B16F10) cells. Q-3-G down-regulated the expression of the pro-inflammatory gene and cytokine such as cyclooxygenase-2 (COX-2) and tumor necrosis factor (TNF)-α in H₂O₂ or UVB-irradiated HaCaT cells. We also showed that Q-3-G exhibits an antioxidant effect using free radical scavenging assays, flow cytometry, and an increased expression of nuclear factor erythroid 2- related factor 2 (Nrf2). Q-3-G reduced melanin production in α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 cells. The hydration effects and mechanisms of Q-3-G were examined by evaluating the moisturizing factor-related genes, such as transglutaminase-1 (TGM-1), filaggrin (FLG), and hyaluronic acid synthase (HAS)-1. In addition, Q-3-G increased the phosphorylation of c-Jun, Jun N-terminal kinase (JNK), Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and TAK1, involved in the MAPKs/AP-1 pathway, and the phosphorylation of IκBα, IκB kinase (IKK)-α, Akt, and Src, involved in the NF-κB pathway. Taken together, we have demonstrated that Q-3-G exerts anti-inflammatory, antioxidant, moisturizing, and antimelanogenesis properties in human keratinocytes and melanoma cells through NF-κB and AP-1 pathways. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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12 pages, 2259 KiB

Open AccessArticle

Isoleucilactucin Ameliorates Coal Fly Ash-Induced Inflammation through the NF-κB and MAPK Pathways in MH-S Cells

by H. M. Arif Ullah, Tae-Hyung Kwon, SeonJu Park, Sung Dae Kim and Man Hee Rhee

Int. J. Mol. Sci. 2021, 22(17), 9506; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179506 - 01 Sep 2021

Cited by 6 | Viewed by 2480

Abstract

We investigated whether isoleucilactucin, an active constituent of Ixeridium dentatum, reduces inflammation caused by coal fly ash (CFA) in alveolar macrophages (MH-S). The anti-inflammatory effects of isoleucilactucin were assessed by measuring the concentration of nitric oxide (NO) and the expression of pro-inflammatory mediators in MH-S cells exposed to CFA-induced inflammation. We found that isoleucilactucin reduced CFA-induced NO generation dose-dependently in MH-S cells. Moreover, isoleucilactucin suppressed CFA-activated proinflammatory mediators, including cyclooxygenase-2 (COX2) and inducible NO synthase (iNOS), and the proinflammatory cytokines such as interleukin-(IL)-1β, IL-6, and tumor necrosis factor (TNF-α). The inhibiting properties of isoleucilactucin on the nuclear translocation of phosphorylated nuclear factor-kappa B (p-NF-κB) were observed. The effects of isoleucilactucin on the NF-κB and mitogen-activated protein kinase (MAPK) pathways were also measured in CFA-stimulated MH-S cells. These results indicate that isoleucilactucin suppressed CFA-stimulated inflammation in MH-S cells by inhibiting the NF-κB and MAPK pathways, which suggest it might exert anti-inflammatory properties in the lung. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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17 pages, 4992 KiB

Open AccessArticle

Mechanisms and Effect of Coptidis Rhizoma on Obesity-Induced Inflammation: In Silico and In Vivo Approaches

by Oh-Jun Kwon, Ji-Won Noh and Byung-Cheol Lee

Int. J. Mol. Sci. 2021, 22(15), 8075; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22158075 - 28 Jul 2021

Cited by 8 | Viewed by 2623

Abstract

Obesity is characterized as a chronic, low-grade inflammation state accompanied by the infiltration of immune cells into adipose tissue and higher levels of inflammatory cytokines and chemokines. This study aimed to investigate the mechanisms and effects of Coptidis Rhizoma (CR) on obesity and its associated inflammation. First, we applied a network pharmacology strategy to search the target genes and pathways regulated by CR in obesity. Next, we performed in vivo experiments to confirm the antiobesity and anti-inflammatory effects of CR. Mice were assigned to five groups: normal chow (NC), control (high-fat diet (HFD)), HFD + CR 200 mg/kg, HFD + CR 400 mg/kg, and HFD + metformin 200 mg/kg. After 16 weeks of the experimental period, CR administration significantly reduced the weight of the body, epididymal fat, and liver; it also decreased insulin resistance, as well as the area under the curve of glucose in the oral glucose tolerance test and triglyceride in the oral fat tolerance test. We observed a decrease in adipose tissue macrophages (ATMs) and inflammatory M1 ATMs, as well as an increase in anti-inflammatory M2 ATMs. Gene expression levels of inflammatory cytokines and chemokines, including tumor necrosis factor-α, F4/80, and C-C motif chemokine (CCL)-2, CCL4, and CCL5, were suppressed in adipose tissue in the CR groups than levels in the control group. Additionally, histological analyses suggested decreased fat accumulation in the epididymal fat pad and liver in the CR groups than that in the control group. Taken together, these results suggest that CR has a therapeutic effect on obesity-induced inflammation, and it functions through the inhibition of macrophage-mediated inflammation in adipose tissue. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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Review

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30 pages, 1714 KiB

Open AccessReview

Ginsenosides from Panax ginseng as Key Modulators of NF-κB Signaling Are Powerful Anti-Inflammatory and Anticancer Agents

by Won Young Jang, Ji Yeon Hwang and Jae Youl Cho

Int. J. Mol. Sci. 2023, 24(7), 6119; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076119 - 24 Mar 2023

Cited by 13 | Viewed by 2268

Abstract

Nuclear factor kappa B (NF-κB) signaling pathways progress inflammation and immune cell differentiation in the host immune response; however, the uncontrollable stimulation of NF-κB signaling is responsible for several inflammatory illnesses regardless of whether the conditions are acute or chronic. Innate immune cells, such as macrophages, microglia, and Kupffer cells, secrete pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, via the activation of NF-κB subunits, which may lead to the damage of normal cells, including neurons, cardiomyocytes, hepatocytes, and alveolar cells. This results in the occurrence of neurodegenerative disorders, cardiac infarction, or liver injury, which may eventually lead to systemic inflammation or cancer. Recently, ginsenosides from Panax ginseng, a historical herbal plant used in East Asia, have been used as possible options for curing inflammatory diseases. All of the ginsenosides tested target different steps of the NF-κB signaling pathway, ameliorating the symptoms of severe illnesses. Moreover, ginsenosides inhibit the NF-κB-mediated activation of cancer metastasis and immune resistance, significantly attenuating the expression of MMPs, Snail, Slug, TWIST1, and PD-L1. This review introduces current studies on the therapeutic efficacy of ginsenosides in alleviating NF-κB responses and emphasizes the critical role of ginsenosides in severe inflammatory diseases as well as cancers. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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24 pages, 3371 KiB

Open AccessReview

Immunopharmacological Activities of Luteolin in Chronic Diseases

by Lei Huang, Mi-Yeon Kim and Jae Youl Cho

Int. J. Mol. Sci. 2023, 24(3), 2136; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032136 - 21 Jan 2023

Cited by 16 | Viewed by 2469

Abstract

Flavonoids have been shown to have anti-oxidative effects, as well as other health benefits (e.g., anti-inflammatory and anti-tumor functions). Luteolin (3′, 4′, 5,7-tetrahydroxyflavone) is a flavonoid found in vegetables, fruits, flowers, and herbs, including celery, broccoli, green pepper, navel oranges, dandelion, peppermint, and rosemary. Luteolin has multiple useful effects, especially in regulating inflammation-related symptoms and diseases. In this paper, we summarize the studies about the immunopharmacological activity of luteolin on anti-inflammatory, anti-cardiovascular, anti-cancerous, and anti-neurodegenerative diseases published since 2018 and available in PubMed or Google Scholar. In this review, we also introduce some additional formulations of luteolin to improve its solubility and bioavailability. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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16 pages, 4096 KiB

Open AccessReview

Apigenin: A Therapeutic Agent for Treatment of Skin Inflammatory Diseases and Cancer

by Ji Hye Yoon, Mi-Yeon Kim and Jae Youl Cho

Int. J. Mol. Sci. 2023, 24(2), 1498; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021498 - 12 Jan 2023

Cited by 19 | Viewed by 5557

Abstract

The skin is the main barrier between the body and the environment, protecting it from external oxidative stress induced by ultraviolet rays. It also prevents the entrance of infectious agents such as viruses, external antigens, allergens, and bacteria into our bodies. An overreaction to these agents causes severe skin diseases, including atopic dermatitis, pruritus, psoriasis, skin cancer, and vitiligo. Members of the flavonoid family include apigenin, quercetin, luteolin, and kaempferol. Of these, apigenin has been used as a dietary supplement due to its various biological activities and has been shown to reduce skin inflammation by downregulating various inflammatory markers and molecular targets. In this review, we deal with current knowledge about inflammatory reactions in the skin and the molecular mechanisms by which apigenin reduces skin inflammation. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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19 pages, 1536 KiB

Open AccessReview

Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites

by Won Young Jang, Mi-Yeon Kim and Jae Youl Cho

Int. J. Mol. Sci. 2022, 23(24), 15482; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232415482 - 07 Dec 2022

Cited by 25 | Viewed by 5133

Abstract

Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent a type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans can be further modified into END or ENL by the activities of gut microbiota. Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer. Interestingly, the molecular mechanisms of lignans in these diseases involve the inhibition of inflammatory signals, including the nuclear factor (NF)-κB pathway. Therefore, we summarize the recent in vitro and in vivo studies evaluating the biological effects of various lignans, focusing on their values as effective anti-inflammatory agents. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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13 pages, 1166 KiB

Open AccessReview

The Role of Thymoquinone in Inflammatory Response in Chronic Diseases

by Yan Liu, Lei Huang, Mi-Yeon Kim and Jae Youl Cho

Int. J. Mol. Sci. 2022, 23(18), 10246; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810246 - 06 Sep 2022

Cited by 11 | Viewed by 2510

Abstract

Anti-inflammatory therapies have been shown to be effective in the prevention of various cardiovascular diseases, tumors, and cancer complications. Thymoquinone (TQ), the main active constituent of Nigella sativa, has shown promising therapeutic properties in many in vivo and in vitro models. However, TQ has poor bioavailability and is hydrophobic, prohibiting clinical trials with TQ alone. Studies have explored the combination of TQ with biological nanomaterials to improve its bioavailability. The TQ nanoparticle formulation shows better bioavailability than free TQ, and these formulations are ready for clinical trials to determine their potential as therapeutic agents. In this paper, we review current knowledge about the interaction between TQ and the inflammatory response and summarize the research prospects in Korea and abroad. We discuss the different biological activities of TQ and various combination therapies of TQ and nanomaterials in clinical trials. Full article

(This article belongs to the Special Issue Molecular Mechanism of Anti-inflammatory Actions of Natural Components)

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