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Satapathy T, Minj A, Verma M. Impact of NSAIDs corticosteroids DMARDs biologics and their comparisons with natural products in C-reactive proteins (CRP) linked cardiovascular disorders. Inflammopharmacology 2025:10.1007/s10787-025-01767-1. [PMID: 40319427 DOI: 10.1007/s10787-025-01767-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 01/20/2025] [Indexed: 05/07/2025]
Abstract
An important part of the pathophysiology of atherosclerosis is the involvement of inflammatory processes, which mediate various stages of the formation of atheroma, from the first leukocyte recruitment to the final rupture of the unstable atherosclerotic plaque. Acute phase reactant C-reactive protein (CRP), which represents varying degrees of inflammation, has been identified as a separate risk factor for several cardiovascular diseases (CVD), particularly unstable coronary syndrome. We hypothesize that CRP is a direct cause of CVD in addition to being an inflammatory marker. Therefore, therapies aimed at lowering CRP should be beneficial for both primary and secondary CVD prevention. It has been demonstrated that the use of many drugs, particularly statins, alters CRP levels while also lowering cardiovascular events. The use of inflammatory biomarkers aids in the discovery of CVDs and tracks the assessment, prognosis, and administration of treatment. An acute-phase protein called C-reactive protein (CRP) is created in response to pro-inflammatory cytokines. CRP is a key modulator of atherosclerosis and a biomarker of the inflammatory response. It is also regarded as a CVD risk factor since it actively promotes the growth of atherosclerotic plaque, instability, and consequent clot. Patients with intermediate risk for cardiovascular diseases have been using the plasma concentration of hsCRP (high sensitivity CRP) as a biomarker for disease prognosis since 2010.
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Affiliation(s)
- Trilochan Satapathy
- Department of Pharmacology, Columbia Institute of Pharmacy, Vill-Tekari, Near Vidhansabha, Raipur, CG, 493111, India
| | - Anjali Minj
- Department of Pharmacology, Columbia Institute of Pharmacy, Vill-Tekari, Near Vidhansabha, Raipur, CG, 493111, India.
| | - Mansi Verma
- Department of Pharmacology, Columbia Institute of Pharmacy, Vill-Tekari, Near Vidhansabha, Raipur, CG, 493111, India
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Valencia J, Yáñez RM, Muntión S, Fernández-García M, Martín-Rufino JD, Zapata AG, Bueren JA, Vicente Á, Sánchez-Guijo F. Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacity. Front Immunol 2025; 16:1473788. [PMID: 40034706 PMCID: PMC11872697 DOI: 10.3389/fimmu.2025.1473788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 01/28/2025] [Indexed: 03/05/2025] Open
Abstract
Introduction MSCs exhibit regenerative, anti-inflammatory and immunomodulatory properties due to the large amount of cytokines, chemokines and growth factors they secrete. MSCs have been extensively evaluated in clinical trials, however, in some cases their therapeutic effects are variable. Therefore, strategies to improve their therapeutic potential, such as preconditioning with proinflammatory factors, have been proposed. Several priming approaches have provided non-conclusive results, and the duration of priming effects on MSC properties or their response to a second inflammatory stimulus have not been fully addressed. Methods We have investigated the impact of triple cytokine priming in MSCs on their characterization and viability, their transcriptomic profile, the functionality of innate and acquired immune cells, as well as the maintenance of the response to priming over time, their subsequent responsiveness to a second inflammatory stimulus. Results Priming MSCs with proinflammatory cytokines (CK-MSCs) do not modify the differentiation capacity of MSCs, nor their immunophenotype and viability. Moreover, cytokine priming enhances the anti-inflammatory and immunomodulatory properties of MSCs against NK and dendritic cells, while maintaining the same T cell immunomodulatory capacity as unstimulated MSCs. Thus, they decrease T-lymphocytes and NK cell proliferation, inhibit the differentiation and allostimulatory capacity of dendritic cells and promote the differentiation of monocytes with an immunosuppressive profile. In addition, we have shown for the first time that proinflammatory priming reduces the variability between different donors and MSC origins. Finally, the effect on CK-MSC is maintained over time and even after a secondary inflammatory stimulus. Conclusions Cytokine-priming improves the therapeutic potential of MSCs and reduces inter-donor variability.
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Affiliation(s)
- Jaris Valencia
- Department of Cell Biology, School of Medicine, Complutense University of Madrid, Madrid, Spain
- Heath Research Institute Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- RICORS TERAV, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Rosa M. Yáñez
- RICORS TERAV, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
- Heath Research Institute-Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain
| | - Sandra Muntión
- RICORS TERAV, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, University of Salamanca and Cell Therapy Area and Hematology Department, IBSAL-University Hospital of Salamanca, Salamanca, Spain
- Regenerative Medicine and Cellular Therapy Network Center of Castilla y León, Salamanca, Spain
| | - María Fernández-García
- RICORS TERAV, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
- Heath Research Institute-Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain
| | - Jorge Diego Martín-Rufino
- Division of Hematology/Oncology, Boston Children’s Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
- Broad Institute of MIT and Harvard, Cambridge, MA, United States
| | - Agustín G. Zapata
- RICORS TERAV, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain
- Heath Research Institute Hospital 12 de Octubre (I+12), Madrid, Spain
| | - Juan A. Bueren
- RICORS TERAV, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
- Heath Research Institute-Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain
| | - Ángeles Vicente
- Department of Cell Biology, School of Medicine, Complutense University of Madrid, Madrid, Spain
- RICORS TERAV, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Heath Research Institute Hospital 12 de Octubre (I+12), Madrid, Spain
| | - Fermín Sánchez-Guijo
- RICORS TERAV, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, University of Salamanca and Cell Therapy Area and Hematology Department, IBSAL-University Hospital of Salamanca, Salamanca, Spain
- Regenerative Medicine and Cellular Therapy Network Center of Castilla y León, Salamanca, Spain
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Choudhary R, Kumar P, Shukla SK, Bhagat A, Anal JMH, Kour G, Ahmed Z. Synthesis and potential anti-inflammatory response of indole and amide derivatives of ursolic acid in LPS-induced RAW 264.7 cells and systemic inflammation mice model: Insights into iNOS, COX2 and NF-κB. Bioorg Chem 2025; 155:108091. [PMID: 39755101 DOI: 10.1016/j.bioorg.2024.108091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 12/13/2024] [Accepted: 12/21/2024] [Indexed: 01/06/2025]
Abstract
Ursolic acid (3-hydroxy-urs-12-ene-28-oic acid, UA) is a pentacyclic triterpene present in numerous plants, fruits and herbs and exhibits various pharmacological effects. However, UA has limited clinical applicability since it is classified as BCS class IV molecule, characterized by low solubility, low oral bioavailability and low permeability. In the present study, UA was isolated from the biomass marc of Lavandula angustifolia and was structurally modified by an induction of indole ring at the C-3 position and amide group at the C-17 position with the aim to enhance its pharmacological potential. This modification resulted in the synthesis of a series of compounds which were investigated for their anti-inflammatory potential both in-vitro and in animal models in comparison to UA. In RAW 264.7 cells, UA and its derivatives were non-cytotoxic up to 10 µM. The derivative UA-1 exhibited a significantly lower IC50 (2.2 ± 0.4 µM) for NO inhibition compared to UA (17.5 ± 2.0 µM). Molecular docking showed strong interactions of UA-1 with TNF-α and NF-κB. UA-1 significantly reduced LPS-induced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in RAW 264.7 macrophages with the inhibition levels of 74.2 ± 2.1 % for TNF-α, 55.9 ± 3.7 % for IL-6 and 59.7 ± 4.2 % for IL-1β at 5.0 µM, respectively and reactive oxygen species while upregulating anti-inflammatory cytokine, IL-10. It also downregulated iNOS, COX-2, p-NF-κB p65, and p-IκBα at both mRNA and protein levels. In LPS-induced systemic inflammation mice model, UA-1 significantly lowered NO, TNF-α, IL-6, IL-1β and serum biochemical parameters, reduced tissue damage, and exhibited improved aqueous solubility and moderate lipophilicity. Overall, UA-1 demonstrated superior anti-inflammatory potential, improved solubility, and better therapeutic potential compared to UA.
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Affiliation(s)
- Rupali Choudhary
- Pharmacology Division, CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Puneet Kumar
- Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Sanket K Shukla
- Pharmacology Division, CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Asha Bhagat
- Pharmacology Division, CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India
| | - Jasha Momo H Anal
- Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
| | - Gurleen Kour
- Pharmacology Division, CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
| | - Zabeer Ahmed
- Pharmacology Division, CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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Shriwash N, Aiman A, Singh P, Basir SF, Shamsi A, Shahid M, Dohare R, Islam A. Understanding the role of potential biomarkers in attenuating multiple sclerosis progression via multiomics and network-based approach. PLoS One 2024; 19:e0314428. [PMID: 39700118 DOI: 10.1371/journal.pone.0314428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 11/10/2024] [Indexed: 12/21/2024] Open
Abstract
BACKGROUND Multiple sclerosis (MS) is a complex neurological disorder marked by neuroinflammation and demyelination. Understanding its molecular basis is vital for developing effective treatments. This study aims to elucidate the molecular progression of MS using multiomics and network-based approach. METHODS We procured differentially expressed genes in MS patients and healthy controls by accessing mRNA dataset from a publicly accessible database. The DEGs were subjected to a non-trait weighted gene co-expression network (WGCN) for hub DEGs identification. These hub DEGs were utilized for enrichment, protein-protein interaction network (PPIN), and feed-forward loop (FFL) analyses. RESULTS We identified 880 MS-associated DEGs. WGCN revealed a total of 122 hub DEGs of which most significant pathway, gene ontology (GO)-biological process (BP), GO-molecular function (MF) and GO-cellular compartment (CC) terms were assembly and cell surface presentation of N-methyl-D-aspartate (NMDA) receptors, regulation of catabolic process, NAD(P)H oxidase H2O2 forming activity, postsynaptic recycling endosome. The intersection of top 10 significant pathways, GO-BP, GO-MF, GO-CC terms, and PPIN top cluster genests identified STAT3 and CREB1 as key biomarkers. Based on essential centrality measures, CREB1 was retained as the final biomarker. Highest-order subnetwork FFL motif comprised one TF (KLF7), one miRNA (miR-328-3p), and one mRNA (CREB1) based on essential centrality measures. CONCLUSIONS This study provides insights into the roles of potential biomarkers in MS progression and offers a system-level view of its molecular landscape. Further experimental validation is needed to confirm these biomarkers' significance, which will lead to early diagnostic and therapeutic advancements.
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Affiliation(s)
- Nitesh Shriwash
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Okhla, New Delhi, India
| | - Ayesha Aiman
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Okhla, New Delhi, India
- Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, Okhla, New Delhi, India
| | - Prithvi Singh
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Okhla, New Delhi, India
| | - Seemi Farhat Basir
- Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, Okhla, New Delhi, India
| | - Anas Shamsi
- Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Mohammad Shahid
- Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Ravins Dohare
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Okhla, New Delhi, India
| | - Asimul Islam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Okhla, New Delhi, India
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Kim H, Shin HY, Park M, Ahn K, Kim SJ, An SH. Exosome-Like Vesicles from Lithospermum erythrorhizon Callus Enhanced Wound Healing by Reducing LPS-Induced Inflammation. J Microbiol Biotechnol 2024; 35:e2410022. [PMID: 39848679 PMCID: PMC11813354 DOI: 10.4014/jmb.2410.10022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/13/2024] [Accepted: 11/18/2024] [Indexed: 01/25/2025]
Abstract
Lithospermum erythrorhizon (LE), a medicinal plant from the Boraginaceae family, is traditionally used in East Asia for its therapeutic effects on skin conditions, including infections, inflammation, and wounds. Recently, the role of extracellular vesicles (EVs) as mediators of intercellular communication that regulate inflammation and promote tissue regeneration has garnered increasing attention in the field of regenerative medicine. This study investigates exosome-like vesicles derived from LE callus (LELVs) and their potential in enhancing wound healing. In vitro studies using normal human dermal fibroblasts (NHDFs) demonstrated that LELVs significantly improved cell viability, proliferation, and wound closure, while also enhancing collagen type I synthesis, indicating anti-inflammatory and regenerative properties. For in vivo analysis, LELVs were applied to lipopolysaccharide (LPS)-induced wounds in mice, where wound healing progression was monitored over 14 days. LELV-treated wounds exhibited accelerated re-epithelialization, reduced inflammation, and improved tissue remodeling, with histological analysis revealing enhanced collagen deposition and reduced inflammatory cell infiltration. These results highlight the ability of LELVs to modulate the inflammatory response and promote wound healing. With their natural origin, low immunogenicity, and ease of production, LELVs represent a promising alternative to synthetic treatments for inflammation-associated skin injuries and hold significant potential for clinical applications in wound care.
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Affiliation(s)
- Hyeonoh Kim
- Preclinical Research Center, Daegu Gyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu 41061, Republic of Korea
| | - Hyun-young Shin
- Research Institute, Sphebio Co., Ltd., Seoul 04796, Republic of Korea
| | - Mira Park
- Research Institute, Sphebio Co., Ltd., Seoul 04796, Republic of Korea
| | - Keunsun Ahn
- Research Institute, Sphebio Co., Ltd., Seoul 04796, Republic of Korea
| | - Seung-Jin Kim
- Research Institute, Sphebio Co., Ltd., Seoul 04796, Republic of Korea
| | - Sang-Hyun An
- Preclinical Research Center, Daegu Gyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu 41061, Republic of Korea
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Værøy H, Skar-Fröding R, Hareton E, Fetissov SO. Possible roles of neuropeptide/transmitter and autoantibody modulation in emotional problems and aggression. Front Psychiatry 2024; 15:1419574. [PMID: 39381606 PMCID: PMC11458397 DOI: 10.3389/fpsyt.2024.1419574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 08/30/2024] [Indexed: 10/10/2024] Open
Abstract
The theoretical foundations of understanding psychiatric disorders are undergoing changes. Explaining behaviour and neuroendocrine cell communication leaning towards immunology represents a different approach compared to previous models for understanding complex central nervous system processes. One such approach is the study of immunoglobulins or autoantibodies, and their effect on peptide hormones in the neuro-endocrine system. In the present review, we provide an overview of the literature on neuropeptide/transmitter and autoantibody modulation in psychiatric disorders featuring emotional problems and aggression, including associated illness behaviour. Finally, we discuss the role of psycho-immunology as a growing field in the understanding of psychiatric disorders, and that modulation and regulation by IgG autoAbs represent a relatively new subcategory in psycho-immunology, where studies are currently being conducted.
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Affiliation(s)
- Henning Værøy
- R&D Department, Division of Mental Health Services, Akershus University Hospital, Lørenskog, Norway
| | - Regina Skar-Fröding
- R&D Department, Division of Mental Health Services, Akershus University Hospital, Lørenskog, Norway
| | - Elin Hareton
- Department of Multidiciplinary Laboratory Medicine and Medical Biochemistry, (TLMB), Akershus University Hospital, Lørenskog, Norway
| | - Sergueï O. Fetissov
- Neuroendocrine, Endocrine and Germinal Differentiation and Communication Laboratory, Inserm UMR1239, University of Rouen Normandie, Rouen, France
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Yu Y, Yu J, Cui X, Sun X, Yu X. TNF-α-induced down-regulation of type I interferon receptor contributes to acquired resistance of cervical squamous cancer to Cisplatin. J Antibiot (Tokyo) 2024; 77:102-110. [PMID: 38102186 DOI: 10.1038/s41429-023-00686-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 10/30/2023] [Accepted: 11/03/2023] [Indexed: 12/17/2023]
Abstract
We aimed to investigate the effects of tumor necrosis factor (TNF)-α on the expression of interferon α/β receptor subunit 1 (IFNAR1) and cervical squamous cancer (CSCC) resistance to Cisplatin, as well as the underlying mechanisms. Kaplan-Meier analysis was used to plot the overall survival curves. SiHa cells were treated with 20 ng/ml TNF-α to determine cell proliferation in human CSCC cells and the expression of IFNAR1. The effects of TNF-α on the downstream signaling pathway, including casein kinase 1α (CK1α), were investigated using the caspase protease inhibitor FK009, the c-Jun kinase inhibitor SP600125, and the nuclear factor kappa-B inhibitor ammonium pyrrolidinedithiocarbamate (PDTC). TNF-α induced down-regulation of IFNAR1 in human CSCC cells and promoted proliferation of SiHa cells. SiHa cells were transfected with the catalytic inactive mutant CK1α K49A, and the ability of TNF-α to induce down-regulation of IFNAR1 expression was found to be significantly diminished in this context. FK009 and PDTC had no obvious effect on the expression of CK1α, however, SP600125 significantly reduced the expression of CK1α in the presence of TNF-α. SiHa cells treated with TNF-α showed reduced sensitivity to Cisplatin and exhibited higher cell viability, while the sensitivity of SiHa cells to Cisplatin was restored after treatment with CK1α inhibitor D4476. Additionally, we constructed a TNF-α overexpressing SiHa cell line and a transplanted tumor model. The results were similar to those of in vitro efficacy. We demonstrate that TNF-α-induced down-regulation of type I interferon receptor contributes to acquired resistance of cervical squamous cancer to Cisplatin.
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Affiliation(s)
- Yani Yu
- Department of Gynecology, Zibo Central Hospital, No. 54 Gongqingtuan West Road, Zibo, 255036, Shandong, China
| | - Jia Yu
- Department of Gynecology, Zibo Central Hospital, No. 54 Gongqingtuan West Road, Zibo, 255036, Shandong, China.
| | - Xiaorong Cui
- Department of Gynecology, Zibo Central Hospital, No. 54 Gongqingtuan West Road, Zibo, 255036, Shandong, China
| | - Xin Sun
- Department of Gynecology, Zibo Central Hospital, No. 54 Gongqingtuan West Road, Zibo, 255036, Shandong, China
| | - Xiaohui Yu
- Department of Gynecology, Zibo Central Hospital, No. 54 Gongqingtuan West Road, Zibo, 255036, Shandong, China
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Aghamohammad S, Sepehr A, Miri ST, Najafi S, Pourshafie MR, Rohani M. Investigation of the anti-inflammatory effects of native potential probiotics as supplementary therapeutic agents in an in-vitro model of inflammation. BMC Complement Med Ther 2023; 23:335. [PMID: 37735396 PMCID: PMC10515064 DOI: 10.1186/s12906-023-04153-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 09/05/2023] [Indexed: 09/23/2023] Open
Abstract
BACKGROUND IBD is considered an inflammatory disease with abnormal and exaggerated immune responses. To control the symptoms, different theraputic agents could be used, however, utilizing the agents with the least side effects could be important. Probiotics as beneficial microorganisms are one of the complementory theraputic agents that could be used to modulate inflammatory signaling pathways. In the current study, we aimed to identify the precise molecular effects of potential probiotics on signaling pathways involved in the development of inflammation. METHODS A quantitative real-time polymerase chain reaction (qPCR) assay was used to analyze the expression of JAK /STAT (JAK1, JAK2, JAK3, TYK2, STAT1, STAT2, STAT3, STAT4, STAT5 and STAT6) and inflammatory genes (NEMO, TIRAP, IRAK, and RIP) after the HT -29 cell line treatment with the sonicated pathogens and potential probiotics. A cytokine assay was also used to evaluate IL -6 and IL -1β production after potential probiotic treatment. RESULTS The potential probiotic cocktail downregulated the JAK genes and TIRAP, IRAK4, NEMO, and RIP genes in the NF-kB pathway compared with cells that were treated with sonicated gram negative pathogens. The expression of STAT genes was different after potential probiotic treatment. The production of IL -6 and IL -1β decreased after potential probiotic treatment. CONCLUSIONS Considering the importance of controlling the symptoms of IBD to improve the life quality of the patients, using probiotic could be crucial. In the current study the studied native potential probiotic cocktails showed anti-inflammatory effects via modulation of JAK /STAT and NF-kB signaling pathways. This observation suggests that our native potential probiotics consumption could be useful in reducing intestinal inflammation.
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Affiliation(s)
| | - Amin Sepehr
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Seyedeh Tina Miri
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Saeideh Najafi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | | | - Mahdi Rohani
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.
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Li C, Wang L, Sun D, Yao T, Xian X, Cheng Y. Colitis induced by PD-1 inhibitor combined with platinum-containing dual drug chemotherapy in Lewis mice and its mechanism. J Cancer Res Ther 2023; 19:939-944. [PMID: 37675720 DOI: 10.4103/jcrt.jcrt_2078_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/08/2023]
Abstract
Aims To explore the occurrence and possible mechanism of colitis in Lewis mice treated with PD-1 inhibitor combined with platinum-containing dual drug chemotherapy. Subjects and Methods A Lewis lung cancer model of C57BL/6 mice was established, randomly divided into the treatment group (group C, PD-1 inhibitor + Carboplatin (CARB) + Pemetrexed (PEM)) and model group (group B, normal saline), and a control group (group A, normal saline) was set up. Observe the changes in tumor-free weight, tumor volume, disease activity index (DAI), colon histopathology, identify serum interleukin (IL)-10, interferon (IFN)-γ, the expression of claudin-1, and occludin mRNA in the colon in each animals. Results Compared with group A, the tumor-free weight of mice in B decreased (P < 0.001), the content of IL-10 in serum increased (P < 0.01), the content of IFN-γ in serum decreased (P < 0.01). Compared with group B, the transplanted tumor volume in C was reduced (P < 0.05), DAI scores of D4 (P < 0.001), and D7 (P < 0.001) were increased, colonic histopathology analysis showed that colitis occurred, serum IL-10 content was decreased (P < 0.05), IFN-γ content was increased (P < 0.05), and the mRNA expression of claudin-1 (P < 0.05) and occludin (P < 0.05) was reduced. Conclusions This treatment can inhibit the growth of transplanted tumors but will cause colitis in Lewis mice. The impairment of intestinal barrier function following administration cause an imbalance in the expression of pro-inflammatory and anti-inflammatory factors in the colon, thus causing colitis.
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Affiliation(s)
- Chunhai Li
- Department of Radiology, The Qilu Hospital of Shandong University, Jinan Shandong, China
| | - Lixin Wang
- Department of School of Nursing and Rehabilitation, Shandong University, Jinan, Shandong, China
| | - Daqian Sun
- Department of Radiology, The Qilu Hospital of Shandong University, Jinan Shandong, China
| | - Tianxiao Yao
- Department of Radiology, The Qilu Hospital of Shandong University, Jinan Shandong, China
| | - Xiuying Xian
- Department of Interventional Department, Jinan Central Hospital, Jinan Shandong, China
| | - Yufeng Cheng
- Department of Radiotherapy, The Qilu Hospital of Shandong University, Jinan, Shandong, China
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Zhang Q, Zhao HJ, Huang LY, Song CL, Li HQ, Zhao XH. Low-level Cu-fortification of bovine lactoferrin: Focus on its effect on in vitro anti-inflammatory activity in LPS-stimulated macrophages. Curr Res Food Sci 2023; 6:100520. [PMID: 37251637 PMCID: PMC10209677 DOI: 10.1016/j.crfs.2023.100520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/12/2023] [Accepted: 05/15/2023] [Indexed: 05/31/2023] Open
Abstract
Bovine lactoferrin (LF) per 1 g was reacted with 0.16, 0.32, and 0.64 mg CuCl2 to reach 10%, 20%, and 40% copper-saturation, respectively, aiming to assess their anti-inflammatory activities to lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The macrophages treated with CuCl2 at 0.051 μg/mL dose did not have obvious change in cell viability, lactate dehydrogenase (LDH) release, and intracellular reactive oxygen species (ROS) production. However, LF and Cu-fortified LF products (10-80 μg/mL doses) mostly showed inhibitory effects on the stimulated macrophages dose-dependently. Moreover, Cu-fortified LF products of lower Cu-fortifying levels at lower doses exerted weaker inhibition on the stimulated macrophages than LF, leading to higher cell viability but decreased LDH release. Meanwhile, LF and Cu-fortified LF products at 10 and 20 μg/mL doses showed different activities to the stimulated cells, via partly decreasing or increasing the production of inflammatory mediators namely prostaglandin E2 (PGE2), nitric oxide, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and ROS production, depending on the used Cu-fortifying and dose levels. Compared with LF, Cu-fortified LF product (Cu-fortifying level of 0.16 mg/g LF) at 10 μg/mL dose showed enhanced inhibition on the production of PGE2, ROS, IL-1β, and TNF-α, evidencing increased anti-inflammatory activity. However, the inhibition of Cu-fortified LF product (Cu-fortifying level of 0.32 mg/g LF) at 20 μg/mL dose on the production of these inflammatory mediators was mostly reduced. It is thus proposed that both Cu-fortifying and dose levels could affect LF's anti-inflammatory activity in LPS-stimulated macrophages, while the Cu-fortifying level of LF could govern activity change.
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Affiliation(s)
- Qiang Zhang
- School of Biological and Food Engineering, Guangdong University of Petrochemical Technology, Maoming, 525000, China
| | - Hui-Juan Zhao
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, 150030, China
| | - Liu-Yan Huang
- School of Biological and Food Engineering, Guangdong University of Petrochemical Technology, Maoming, 525000, China
| | - Chun-Li Song
- College of Food and Bioengineering, Qiqihar University, Qiqihar, 161006, China
| | - Hua-Qiang Li
- School of Biological and Food Engineering, Guangdong University of Petrochemical Technology, Maoming, 525000, China
| | - Xin-Huai Zhao
- School of Biological and Food Engineering, Guangdong University of Petrochemical Technology, Maoming, 525000, China
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, 150030, China
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming, 525000, China
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11
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YÜKSEL TN, YAYLA M, KÖSE D, UĞAN RA, TOKTAY E, AKSU KILIÇLE P, ÇADIRCI E, HALICI Z. INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS. TRAKYA UNIVERSITY JOURNAL OF NATURAL SCIENCES 2023; 24:11-20. [DOI: 10.23902/trkjnat.1145462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Pomegranate peel contains bioactive ingredients such as flavonoids, ellagitannins, phenolics and proanthocyanidin compounds with high antioxidant activity. Pomegranate peel has antiapoptotic, antioxidant and anti-inflammatory effects due to its high punicalagin content. We aimed to determine the effect of pomegranate peel extract (PPE) on lipopolysaccharide (LPS)-induced uveitis. Sixty rats were seperated randomly into twelve groups (n = 5). The healthy group received intraperitoneal normal saline, the uveitis group received 200 μg/kg LPS, the dexamethasone (DEX) group received 200 μg/kg LPS plus 1 mg/kg DEX, the PPE100, PPE300 and PPE500 groups received 200 μg/kg LPS plus 100, 300 and 500 mg/kg PPE, respectively. The eye tissues were collected at 3rd and 24th hour. and investigated molecularly (Relative quantification of gene expression), biochemically (Superoxide dismutase activity, Glutathione and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Tumor Necrosis Factor-α, vascular endothelial growth factor, and Caspase-3 levels markedly decreased in a dose-dependent manner in the uveitic rats following PPE administration. PPE administration significantly ameliorated uveitic disorders in oxidative stress factors including Glutathione, Superoxide dismutase and Malondialdehyde, with its effects raising in a dose-dependent manner. PPE eliminated histopathological changes in eye tissues due to uveitis. PPE can be a promising agent by contributing to alternative preventive treatment methods for uveitis with its anti-inflammatory, antioxidative, antiapoptotic and antiangiogenic effects.
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Affiliation(s)
| | - Muhammed YAYLA
- KAFKAS ÜNİVERSİTESİ, TIP FAKÜLTESİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, TIBBİ FARMAKOLOJİ ANABİLİM DALI
| | | | - Rüstem Anıl UĞAN
- ATATÜRK ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ, ECZACILIK MESLEK BİLİMLERİ BÖLÜMÜ, FARMAKOLOJİ ANABİLİM DALI
| | - Erdem TOKTAY
- KAFKAS ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, HİSTOLOJİ VE EMBRİYOLOJİ ANABİLİM DALI
| | - Pinar AKSU KILIÇLE
- KAFKAS ÜNİVERSİTESİ, FEN-EDEBİYAT FAKÜLTESİ, BİYOLOJİ BÖLÜMÜ, BİYOLOJİ PR
| | - Elif ÇADIRCI
- ATATÜRK ÜNİVERSİTESİ, TIP FAKÜLTESİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, TIBBİ FARMAKOLOJİ ANABİLİM DALI
| | - Zekai HALICI
- ATATÜRK ÜNİVERSİTESİ, TIP FAKÜLTESİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, TIBBİ FARMAKOLOJİ ANABİLİM DALI
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12
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Yuksel TN, Yayla M, Kose D, Halici Z, Bozkurt E, Toktay T. Protective effects of melatonin receptor agonists on endotoxin-induced uveitis in rats. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2023; 26:540-548. [PMID: 37051104 PMCID: PMC10083838 DOI: 10.22038/ijbms.2023.67297.14749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 02/05/2023] [Indexed: 04/14/2023]
Abstract
OBJECTIVES Melatonin has an important role in regulating a variety of physiological functions of the body. We investigated the protective effects of Agomelatine (AGO) and Ramelteon (RAME) on Endotoxin-Induced Uveitis (EIU) in rats. MATERIALS AND METHODS 70 rats were randomly divided into fourteen groups. Healthy group normal saline, (IP), Uveitis group (200 μg/kg lipopolysaccharide (LPS), SC), DEX group (200 μg/kg LPS plus 1 mg/kg dexamethasone, IP), AGO20 group received 200 μg/kg LPS plus 20 mg/kg AGO, AGO40 group received 200 μg/kg LPS plus 40 mg/kg AGO, RAME2 group received 200 μg/kg LPS plus 2 mg/kg RAME, and group RAME4 received 200 μg/kg LPS plus 4 mg/kg RAME. Each group had two subgroups: the 3rd and 24th hr. The eye tissues were collected and investigated biomicroscopically (clinical manifestations and scoring, molecularly(qRT-PCR analyses of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and caspase 3 and caspase 9 mRNA expression), biochemically (Superoxide dismutase activity (SOD), Glutathione (GSH), and malondialdehyde levels (MDA)) and histopathologically (staining with Harris Hematoxylin and Eosin Y). RESULTS Melatonin receptor agonist treatment reduced the clinical score count of ocular inflammation in the uveitic rats. TNF-α, VEGF, caspase 9, and caspase 3 levels markedly decreased in the uveitic rats. Melatonin receptor agonists significantly ameliorated fixed changes in GSH, SOD, and MDA levels. Melatonin receptor agonists also ameliorated histopathological injury in eye tissues associated with uveitis. CONCLUSION Melatonin receptor agonists ameliorated the inflammatory response in EIU. These findings suggest that melatonin receptor agonists may represent a potential novel therapeutic drug for uveitis treatment.
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Affiliation(s)
- Tugba Nurcan Yuksel
- Department of Pharmacology, Faculty of Medicine, Tekirdag Namık Kemal University, Tekirdag, Turkey
| | - Muhammed Yayla
- Department of Pharmacology, Faculty of Medicine, Kafkas University, Kars, Turkey
| | - Duygu Kose
- Department of Pharmacology, Faculty of Medicine, Sutcu Imam University, Kahramanmaraş, Turkey
| | - Zekai Halici
- Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
- Clinical Research, Development and Design Application and Research Center, Ataturk University, Erzurum, Turkey
| | - Erdinc Bozkurt
- Department of Ophthalmology, University of Health Science, Ümraniye Education and Research Hospital, Department of Ophthalmology, Istanbul, Turkey
| | - Toktay Toktay
- Department of Histology and Embryology, Faculty of Medicine, Kafkas University, Kars, Turkey
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13
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El Azab EF, Saleh AM, Yousif SO, Mazhari BBZ, Abu Alrub H, Elfaki EM, Hamza A, Abdulmalek S. New insights into geraniol's antihemolytic, anti-inflammatory, antioxidant, and anticoagulant potentials using a combined biological and in silico screening strategy. Inflammopharmacology 2022; 30:1811-1833. [PMID: 35932440 DOI: 10.1007/s10787-022-01039-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 07/15/2022] [Indexed: 11/05/2022]
Abstract
The study aims to assess the antihemolytic and antioxidant activities of geraniol versus 2, 2'-azobis, 2-amidinopropane dihydro-chloride- (AAPH-) induced oxidative damage and hemolysis to erythrocytes and its anti-inflammatory potential against lipopolysaccharide- (LPS-) induced inflammation in white blood cells (WBCs) with a focus on its integrated computational strategies against different targeted receptors participating in inflammation and coagulation. The rats' erythrocyte suspension was incubated with different geraniol concentrations. Molecular docking and simulation were used to explore the possible interaction patterns of geraniol against the potential targeted proteins for therapeutic screening. The results displayed that geraniol had a prolonged noteworthy effect on activated partial thromboplastin time and thromboplastin time. Geraniol displayed strong antioxidant effects via reduced malondialdehyde (MDA) formation and increased GSH level and SOD activity. We observed dose-dependent prevention of K+ ion leakage along with a remarkable decline of hemolysis in erythrocytes pretreated with geraniol. Geraniol 100 µg/mL and diclofenac 100 µM were nontoxic to WBCs. Geraniol significantly reduces the expression and release of cellular pro-inflammatory factors TNF-α, IL-1β, IL-8, and nitric oxide, accompanied by a significant upregulation of gene expression of anti-inflammatory cytokine IL-10 in LPS-induced WBCs compared to nontreated cells. It demonstrates a much stronger inhibition potential than diclofenac in terms of inflammation inhibition. When comparing molecular docking and simulation data, current work showed that geraniol has a good affinity toward apoptosis signal-regulating kinase 1 (ASK1) and human P2Y12 receptors and could be developed as an antioxidant, anti-inflammatory, and anticoagulant medication in the future. Consequently, geraniol is recommended to have a defensive influence against oxidative stress, and hemolysis also could be developed as a promising anti-inflammatory, antioxidant, and anticoagulant medication.
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Affiliation(s)
- Eman Fawzy El Azab
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences at Al-Qurayyat, Jouf University, Al-Qurayyat, 77454, Saudi Arabia. .,Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt.
| | - Abdulrahman M Saleh
- Pharmaceutical Medicinal Chemistry and Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt
| | - Sara Osman Yousif
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences at Al-Qurayyat, Jouf University, Al-Qurayyat, 77454, Saudi Arabia.,Department of Clinical Chemistry, Faculty of Medical Laboratory Sciences, Sudan University of Science and Technology, Khartoum, Sudan
| | - Bi Bi Zainab Mazhari
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences at Al-Qurayyat, Jouf University, Al-Qurayyat, 77454, Saudi Arabia
| | - Heba Abu Alrub
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences at Al-Qurayyat, Jouf University, Al-Qurayyat, 77454, Saudi Arabia
| | - Elyasa Mustafa Elfaki
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences at Al-Qurayyat, Jouf University, Al-Qurayyat, 77454, Saudi Arabia
| | - Alneil Hamza
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences at Al-Qurayyat, Jouf University, Al-Qurayyat, 77454, Saudi Arabia
| | - Shaymaa Abdulmalek
- Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt
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14
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Chojnacka K, Lewandowska U. Inhibition of Pro-Inflammatory Cytokine Secretion by Polyphenol-Rich Extracts in Macrophages via NF-κB Pathway. FOOD REVIEWS INTERNATIONAL 2022. [DOI: 10.1080/87559129.2022.2071936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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15
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Macrophage immunity promotion effect of polysaccharide LGP-1 from Guapian tea via PI3K/AKT and NF-κB signaling pathway. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.104946] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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16
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The Enhancing Immune Response and Anti-Inflammatory Effects of Caulerpa lentillifera Extract in RAW 264.7 Cells. Molecules 2021; 26:molecules26195734. [PMID: 34641278 PMCID: PMC8510275 DOI: 10.3390/molecules26195734] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/15/2021] [Accepted: 09/20/2021] [Indexed: 11/16/2022] Open
Abstract
Background: Caulerpa lentillifera (CL) is a green seaweed, and its edible part represents added value as a functional ingredient. CL was dried and extracted for the determination of its active compounds and the evaluation of its biological activities. The major constituents of CL extract (CLE), including tannic acid, catechin, rutin, and isoquercetin, exhibited beneficial effects, such as antioxidant activity, anti-diabetic activity, immunomodulatory effects, and anti-cancer activities in in vitro and in vivo models. Whether CLE has an anti-inflammatory effect and immune response remains unclear. Methods: This study examined the effect of CLE on the inflammatory status and immune response of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the mechanisms involved therein. RAW264.7 cells were treated with different concentrations of CLE (0.1–1000 µg/mL) with or without LPS (1 µg/mL) for 24 h. Expression and production of the inflammatory cytokines, enzymes, and mediators were evaluated. Results: CLE suppressed expression and production of the pro-inflammatory cytokines IL-6 and TNF-α. Moreover, CLE inhibited expression and secretion of the inflammatory enzyme COX-2 and the mediators PGE2 and NO. CLE also reduced DNA damage. Furthermore, CLE stimulated the immune response by modulating the cell cycle regulators p27, p53, cyclin D2, and cyclin E2. Conclusions: CLE inhibits inflammatory responses in LPS-activated macrophages by downregulating inflammatory cytokines and mediators. Furthermore, CLE has an immunomodulatory effect by modulating cell cycle regulators.
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17
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Wang X, Li F, Li Y, Sun L, Meng Y, Fan X, Wang X, Wu D, Cheng Y, Hua F. Decreased levels of immune-regulatory cytokines in patients with immune thrombocytopenia and long-lasting overexpression of these cytokines in the splenectomized patients. J Leukoc Biol 2021; 110:335-341. [PMID: 34318945 DOI: 10.1002/jlb.5ab0521-621rr] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 05/23/2021] [Accepted: 06/07/2021] [Indexed: 12/31/2022] Open
Abstract
Immune thrombocytopenia (ITP) is an autoimmune-mediated disease characterized by decreased platelet counts. Cytokines play important roles in modulating the immune response and are involved in the pathogenesis of many autoimmune diseases. This study aimed at exploring the serum levels of a core set of cytokines that exert immune-regulatory functions in newly diagnosed ITP patients (both before and after treatment) and splenectomized ITP patients. Using the Bio-Plex suspension array system and ELISA, the serum levels of IL-10, IL-21, IL-27, IL-33, IL-35, IL-37, and TGF-β1 were detected. The data showed that the serum levels of the immune regulatory cytokines IL-10, IL-35, and TGF-β1 were significantly lower in newly diagnosed ITP patients. Decreased cytokine levels could be improved in patients with a complete response or a response after steroid-based treatment(s). The serum concentrations of TGF-β1 were positively correlated with the platelet counts both before and after treatment. All the detected immune-regulatory cytokines, except IL-37, showed significantly higher levels in splenectomized ITP patients than pretreatment ITP patients and healthy controls. In conclusion, these data suggest that lower levels of immune-regulatory cytokines are involved in the pathogenesis of ITP and that there is a long-lasting overexpression of immune-regulatory cytokines in ITP patients with splenectomy.
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Affiliation(s)
- Xiaofeng Wang
- Department of Hematology, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China.,Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Feng Li
- Department of Hematology, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China.,Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yang Li
- Department of Hematology, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China
| | - Lihua Sun
- Department of Hematology, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China
| | - Yahong Meng
- Department of Hematology, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China
| | - Xiaohong Fan
- Department of Hematology, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China
| | - Xuelian Wang
- Department of Hematology, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China
| | - Duojiao Wu
- Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China.,Institute of Clinical Science, Zhongshan Hospital Fudan University, Shanghai, China
| | - Yunfeng Cheng
- Department of Hematology, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China.,Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China.,Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China.,Institute of Clinical Science, Zhongshan Hospital Fudan University, Shanghai, China
| | - Fanli Hua
- Department of Hematology, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China
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18
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Mukherjee S, Kar A, Khatun N, Datta P, Biswas A, Barik S. Familiarity Breeds Strategy: In Silico Untangling of the Molecular Complexity on Course of Autoimmune Liver Disease-to-Hepatocellular Carcinoma Transition Predicts Novel Transcriptional Signatures. Cells 2021; 10:1917. [PMID: 34440687 PMCID: PMC8394127 DOI: 10.3390/cells10081917] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/07/2021] [Accepted: 07/16/2021] [Indexed: 12/17/2022] Open
Abstract
Autoimmune liver diseases (AILD) often lead to transformation of the liver tissues into hepatocellular carcinoma (HCC). Considering the drawbacks of surgical procedures in such cases, need of successful non-invasive therapeutic strategies and treatment modalities for AILD-associated-HCC still exists. Due to the lack of clear, sufficient knowledge about factors mediating AILD-to-HCC transition, an in silico approach was adopted to delineate the underlying molecular deterministic factors. Parallel enrichment analyses on two different public microarray datasets (GSE159676 and GSE62232) pinpointed the core transcriptional regulators as key players. Correlation between the expression kinetics of these transcriptional modules in AILD and HCC was found to be positive primarily with the advancement of hepatic fibrosis. Most of the regulatory interactions were operative during early (F0-F1) and intermediate fibrotic stages (F2-F3), while the extent of activity in the regulatory network considerably diminished at late stage of fibrosis/cirrhosis (F4). Additionally, most of the transcriptional targets with higher degrees of connectivity in the regulatory network (namely DCAF11, PKM2, DGAT2 and BCAT1) may be considered as potential candidates for biomarkers or clinical targets compared to their low-connectivity counterparts. In summary, this study uncovers new possibilities in the designing of novel prognostic and therapeutic regimen for autoimmunity-associated malignancy of liver in a disease progression-dependent fashion.
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Affiliation(s)
- Soumyadeep Mukherjee
- Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata 700026, India; (S.M.); (P.D.)
| | - Arpita Kar
- Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata 700026, India; (A.K.); (N.K.)
| | - Najma Khatun
- Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata 700026, India; (A.K.); (N.K.)
| | - Puja Datta
- Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata 700026, India; (S.M.); (P.D.)
| | - Avik Biswas
- Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata 700026, India; (A.K.); (N.K.)
| | - Subhasis Barik
- Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata 700026, India; (S.M.); (P.D.)
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19
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Su J, Li Q, Liu J, Wang H, Li X, Wüntrang D, Liu C, Zhao Q, RuyuYao, Meng X, Zhang Y. Ethyl acetate extract of Tibetan medicine Rhamnella gilgitica ameliorated type II collagen-induced arthritis in rats via regulating JAK-STAT signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2021; 267:113514. [PMID: 33223115 DOI: 10.1016/j.jep.2020.113514] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 10/16/2020] [Accepted: 10/21/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rhamnella gilgitica Mansf. et Melch. (སེང་ལྡེང་།, RG) is a traditional Tibetan medicinal plant that is currently grown throughout Tibet. According to the theory of Tibetan medicine, RG is efficient for removing rheumatism, reducing swelling, and relieving pain. Hence, it has been used for the treatment of rheumatoid arthritis (RA) in Tibet for many years. However, there are no previous reports on the anti-RA activities of ethyl acetate extract of RG (RGEA). AIM OF THE STUDY This study aimed to explore the anti-RA effect and mechanism of RGEA on collagen-induced arthritis (CIA) in rats. MATERIALS AND METHODS The CIA model was established in male Wister rats by intradermal injection of bovine type II collagen and Complete Freund's Adjuvant at the base of the tail and left sole, respectively. The rats were orally administered with RGEA (9.71, 19.43, or 38.85 mg/kg) for 23 days. The body weight, swelling volume, arthritis index score, thymus and spleen indices, and pathological changes were observed to evaluate the effect of RGEA on RA. Furthermore, the inflammatory cytokines in serum, such as interleukin1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin6 (IL-6), interleukin17 (IL-17), interferon-γ (INF-γ), interleukin4 (IL-4), and interleukin10 (IL-10) were measured by enzyme linked immunosorbent assay (ELISA) to explore the anti-inflammatory effects of RGEA. The terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining was used to examine apoptosis. Finally, the protein and gene expression of B-cell lymphoma-2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), Caspase3, janus-activated kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling1 (SOCS1), and 3 (SOCS3) in synovial tissue were detected using immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS After the treatment with RGEA, the body weight of rats was restored, both the arthritis index and paw swelling were suppressed, and spleen and thymus indices were decreased. RGEA reduced the inflammatory cells and synovial hyperplasia in the synovial tissue of the knee joint, and suppressed bone erosion. Meanwhile, RGEA decreased the levels of IL-1β, IL-6, IL-17, TNF-α, and INF-γ, while increased the levels of IL-4 and IL-10. TUNEL fluorescence apoptosis results confirmed that RGEA obviously promoted the apoptosis of synovial cells. Further studies showed that RGEA inhibited the proteins and mRNAs expression of JAK2 and STAT3 as well as increased the proteins and mRNAs expression of SOCS1 and SOCS3. In addition, RGEA upregulated the expression of Bax and Caspase3, and downregulated the expression of Bcl-2. CONCLUSION The anti-RA effectof RGEA might be related to the promotion of apoptosis and inhibition of inflammation, which regulated the JAK-STAT pathway.
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Affiliation(s)
- Jinsong Su
- Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
| | - Qiuyue Li
- Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
| | - Jia Liu
- Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
| | - Hongling Wang
- Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
| | - Xuanhao Li
- Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
| | - Dhondrup Wüntrang
- Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
| | - Chuan Liu
- Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
| | - Qian Zhao
- Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
| | - RuyuYao
- Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100193,China
| | - Xianli Meng
- Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
| | - Yi Zhang
- Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China.
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Discovery of natural anti-inflammatory alkaloids: Potential leads for the drug discovery for the treatment of inflammation. Eur J Med Chem 2021; 213:113165. [PMID: 33454546 DOI: 10.1016/j.ejmech.2021.113165] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 01/04/2021] [Accepted: 01/05/2021] [Indexed: 02/07/2023]
Abstract
Inflammation is an adaptive response of the immune system to tissue malfunction or homeostatic imbalance. Corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently applied to treat varieties of inflammatory diseases but are associated with gastrointestinal, cardiovascular, and kidney side effects. Developing more effective and less toxic agents remain a challenge for pharmaceutical chemist due to the complexity of the different inflammatory processes. Alkaloids are widely distributed in plants with diverse anti-inflammatory activities, providing various potential lead compounds or candidates for the design and discovery of new anti-inflammatory drug candidates. Therefore, re-examining the anti-inflammatory alkaloid natural products is advisable, bringing more opportunities. In this review, we summarized and described the recent advances of natural alkaloids with anti-inflammatory activities and possible mechanisms in the period from 2009 to 2020. It is hoped that this review of anti-inflammatory alkaloids can provide new ideas for researchers engaged in the related fields and potential lead compounds for the discovery of anti-inflammatory drugs.
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Mohammadian Haftcheshmeh S, Khosrojerdi A, Aliabadi A, Lotfi S, Mohammadi A, Momtazi-Borojeni AA. Immunomodulatory Effects of Curcumin in Rheumatoid Arthritis: Evidence from Molecular Mechanisms to Clinical Outcomes. Rev Physiol Biochem Pharmacol 2021; 179:1-29. [PMID: 33404796 DOI: 10.1007/112_2020_54] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disorder characterized by the destruction of the joint and bone resorption. The production of pro-inflammatory cytokines and chemokines, dysregulated functions of three important subtypes of T helper (TH) cells including TH1, TH17, and regulator T (Treg) cells are major causes of the initiation and development of RA. Moreover, B cells as a source of the production of several autoantibodies play key roles in the pathogenesis of RA. The last decades have seen increasingly rapid advances in the field of immunopharmacology using natural origin compounds for the management of various inflammatory diseases. Curcumin, a main active polyphenol compound isolated from turmeric, curcuma longa, possesses a wide range of pharmacologic properties for the treatment of several diseases. This review comprehensively will assess beneficial immunomodulatory effects of curcumin on the production of pro-inflammatory cytokines and also dysregulated functions of immune cells including TH1, TH17, Treg, and B cells in RA. We also seek the clinical efficacy of curcumin for the treatment of RA in several recent clinical trials. In conclusion, curcumin has been found to ameliorate RA complications through modulating inflammatory and autoreactive responses in immune cells and synovial fibroblast cells via inhibiting the expression or function of pro-inflammatory mediators, such as nuclear factor-κB (NF-κB), activated protein-1 (AP-1), and mitogen-activated protein kinases (MAPKs). Of note, curcumin treatment without any adverse effects can attenuate the clinical symptoms of RA patients and, therefore, has therapeutic potential for the treatment of the diseases.
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Affiliation(s)
| | - Arezou Khosrojerdi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ali Aliabadi
- Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Shadi Lotfi
- Department of Medical Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Asadollah Mohammadi
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
| | - Amir Abbas Momtazi-Borojeni
- Halal Research center of IRI, FDA, Tehran, Iran.
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Bakr RM, Sayed DS, Abd-Elkader AS, Kamel AA, Badran AY. Does interleukin-33 level correlate with the activity of Pemphigus vulgaris?: A case-control study. Dermatol Ther 2020; 34:e14605. [PMID: 33249704 DOI: 10.1111/dth.14605] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/09/2020] [Accepted: 11/26/2020] [Indexed: 11/28/2022]
Abstract
Pemphigus is a group of immune-mediated blistering diseases of skin and mucus membrane caused by destruction of the intercellular junction (desmosomes) by autoantibodies. Pemphigus vulgaris (PV) is considered the most common type of all pemphigus family. Various cytokines play a major role in pemphigus pathogenesis. Interleukin-33 (IL-33) role has been studied in various autoimmune diseases as; psoriasis and rheumatoid arthritis, yet it has not been studied in Egyptian patients with PV. The study aimed to evaluate the possible role of IL-33 in PV by assessing its level in the serum using ELISA and to detect its correlation with activity score using Pemphigus Disease Area Index (PDAI). Forty-four patients with PV and 36 age and sex-matched healthy controls were enrolled in the study. After full history taking and complete dermatological examination, the severity score was calculated using PDAI, then serum samples were taken from each patient and control subjects and subjected to quantitative measurement of serum IL-33 using ELISA. Serum level of IL-33 is significantly raised in PV patients compared to control subjects (P-value = .007). The level of IL-33 was found to be strongly correlated with the activity of the disease measured by PDAI. IL-33 might have a role in PV pathogenesis as shown by its rising level in PV patients. In addition, serum level of IL-33 is strongly correlated with the activity of PV. Thus, we suspect that IL-33 can be used as marker for monitoring PV severity and measuring treatment efficacy.
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Affiliation(s)
- Radwa M Bakr
- Department of Dermatology, Venereology and Andrology, Assiut University, Assiut, Egypt
| | - Doaa S Sayed
- Department of Dermatology, Venereology and Andrology, Assiut University, Assiut, Egypt
| | | | - Amira A Kamel
- Department of Medical Biochemistry, Assiut University, Assiut, Egypt
| | - Aya Y Badran
- Department of Dermatology, Venereology and Andrology, Assiut University, Assiut, Egypt
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Interactions between tumor-derived proteins and Toll-like receptors. Exp Mol Med 2020; 52:1926-1935. [PMID: 33299138 PMCID: PMC8080774 DOI: 10.1038/s12276-020-00540-4] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/20/2020] [Accepted: 11/02/2020] [Indexed: 12/23/2022] Open
Abstract
Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy. In the tumor microenvironment, DAMPs can be ligands for Toll-like receptors (TLRs) expressed on immune cells and induce cytokine production and T-cell activation. Moreover, DAMPs released from tumor cells can directly activate tumor-expressed TLRs that induce chemoresistance, migration, invasion, and metastasis. Furthermore, DAMP-induced chronic inflammation in the tumor microenvironment causes an increase in immunosuppressive populations, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Therefore, regulation of DAMP proteins can reduce excessive inflammation to create an immunogenic tumor microenvironment. Here, we review tumor-derived DAMP proteins as ligands of TLRs and discuss their association with immune cells, tumors, and the composition of the tumor microenvironment. Tumor cells killed by radiotherapy or chemotherapy release signaling molecules that stimulate both immune response and tumor aggressiveness; regulating these molecules could improve treatment efficacy. Tae Heung Kang, Yeong-Min Park, and co-workers at Konkuk University, Seoul, South Korea, have reviewed the role of damage-associated molecular patterns (DAMPs) in immunity and cancer. These signaling molecules act as danger signals, activating immune cells by binding to specific receptors. However, tumor cells have the same receptors, and DAMPs binding triggers chemoresistance and increases invasiveness. The researchers report that although DAMPs can trigger a helpful immune response, they can also cause chronic inflammation, which in turn promotes an immune suppression response, allowing tumors to escape immune detection. Improving our understanding of the functions of different DAMPs could improve our ability to boost the immune response and decrease tumor aggressiveness.
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Jafari T, Fallah AA, Reyhanian A, Sarmast E. Effects of pomegranate peel extract and vitamin E on the inflammatory status and endothelial function in hemodialysis patients: a randomized controlled clinical trial. Food Funct 2020; 11:7987-7993. [PMID: 32839797 DOI: 10.1039/d0fo01012j] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Inflammation and endothelial dysfunction are major problems in hemodialysis (HD) patients. This study assessed the effects of an 8 week administration of pomegranate peel extract (PPE) and vitamin E (Vit E) alone or in combination on the biomarkers of inflammation, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and the biomarkers of endothelial function, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin, in HD patients. In a randomized, double-blind, parallel, placebo-controlled trial, 100 HD patients were randomly divided into 4 equal groups: (a) PPE + Vit E, received 2 pomegranate tablets (each tablet contained 225 mg PPE, equal to 90 mg ellagic acid) + 1 Vit E soft gel (400 IU) daily, (b) PPE, received 2 pomegranate tablets + 1 Vit E placebo soft gel daily, (c) Vit E, received 1 Vit E soft gel + 2 pomegranate placebo tablets daily, and (d) placebo, received 2 pomegranate placebo tablets + 1 Vit E placebo soft gel daily. For group allocation, a stratified block randomization procedure based on sex, age, and HD duration was used. Each intervention product and its placebo had identical shape, color, size, and packaging. Consumption of PPE + Vit E significantly reduced the serum CRP level (mean change: -7.12 ± 4.59 mg l-1, P < 0.001) compared to other groups, while reduced levels of IL-6 (mean change: -2.19 ± 2.33 pg ml-1, P < 0.001), TNF-α (mean change: -2.41 ± 3.21 pg ml-1, P = 0.008), ICAM-1 (mean change: -64.2 ± 111.0 ng ml-1, P = 0.017), and VCAM-1 (mean change: -117.7 ± 177.1 ng ml-1, P = 0.002) were observed compared to the control. There was no significant difference in the P-selectin level among the groups. Consumption of PPE or Vit E alone significantly reduced the CRP level (mean change for PPE: -3.58 ± 5.41 mg l-1, P < 0.001; mean change for Vit E: -3.25 ± 8.29 mg l-1, P = 0.002) compared to the control. As a result, consumption of PPE in combination with Vit E enhanced the inflammatory status and endothelial function in HD patients.
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Affiliation(s)
- Tina Jafari
- Department of Biochemistry and Nutrition, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Aziz A Fallah
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord 34141, Iran
| | - Ali Reyhanian
- Department of Biochemistry and Nutrition, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Elham Sarmast
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord 34141, Iran
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Lee SA, Park BR, Moon SM, Han SH, Kim CS. Anti-inflammatory potential of Trifolium pratense L. leaf extract in LPS-stimulated RAW264.7 cells and in a rat model of carrageenan-induced inflammation. Arch Physiol Biochem 2020; 126:74-81. [PMID: 30320514 DOI: 10.1080/13813455.2018.1493607] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
This study evaluated the anti-inflammatory potential of a 40% prethanol extract of Trifolium pratense leaves (40% PeTP) using in vitro (RAW264.7 cells) and in vivo (carrageenan-induced inflammation model) experiments. Pretreatment with 40% PeTP significantly inhibited the LPS-induced expression of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines, including tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in RAW264.7 cells, without inducing cytotoxicity. The inhibitory effects of 40% PeTP are mediated through suppression of the nuclear translocation of nuclear factor (NF)-κB and the phosphorylation of mitogen-activated protein kinases (MAPKs). Oral administration of 40% PeTP at 50, 100, and 200 mg/kg of body weight suppressed carrageenan-induced oedema in a dose-dependent manner. Collectively, our results suggested that 40% PeTP exerts potential anti-inflammatory effects by suppressing the activation of the NF-κB and MAPK pathways in vitro, and by reducing carrageenan-induced paw oedema in vivo.
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Affiliation(s)
- Seul Ah Lee
- Department of Oral Biochemistry, College of Dentistry, Chosun University, Gwangju, Republic of Korea
| | - Bo-Ram Park
- Department of Dental Hygiene, Chodang University, Muan, Republic of Korea
| | - Sung-Min Moon
- CStech Research Institute, Gwangju, Republic of Korea
| | - Seul Hee Han
- CStech Research Institute, Gwangju, Republic of Korea
| | - Chun Sung Kim
- Department of Oral Biochemistry, College of Dentistry, Chosun University, Gwangju, Republic of Korea
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Kim TY, Yoon E, Lee D, Imm JY. Antioxidant and anti-inflammatory activities of Platycodon grandiflorum seeds extract. CYTA - JOURNAL OF FOOD 2020. [DOI: 10.1080/19476337.2020.1770336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
- Tae Yeong Kim
- Department of Foods and Nutrition, Kookmin University, Seoul, Republic of Korea
| | - Eseo Yoon
- Department of Foods and Nutrition, Kookmin University, Seoul, Republic of Korea
| | - Dabeen Lee
- Research Group of Food Processing, Korea Food Research Institute, Jeollabuk-do, Korea
| | - Jee-Young Imm
- Department of Foods and Nutrition, Kookmin University, Seoul, Republic of Korea
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Zhao YL, Yang XW, Wu BF, Shang JH, Liu YP, Luo XD. Anti-inflammatory Effect of Pomelo Peel and Its Bioactive Coumarins. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:8810-8818. [PMID: 31318199 DOI: 10.1021/acs.jafc.9b02511] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Citrus grandis (L.) Osbeck is a popular fruit cultivated around the world, and its peels are sometimes used for the treatment of cough, abdominal pain, and indigestion in China. However, the peel is discarded after fruit consumption in most cases, and its chemical constituents and biological activities have not been validated before. The present study focused on evaluation of the chemical and pharmacological profile of coumarins from peels of C. grandis against inflammation. The extracts and phytochemicals from peels of C. grandis were prepared, and anti-inflammatory activities were carried out in vivo and in vitro, including inhibiting xylene-induced ear edema and carrageenan-induced paw edema in mice and the production of inflammatory cytokines (interleukin 1β, prostaglandin 2, and tumor-necrosis factor α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results indicated that methanolic extract, ethyl acetate fraction, and four major coumarins (compounds 7, 8, 13, and 16) inhibited swelling induced by xylene and carrageenan, separately, in vivo. Furthermore, 18 coumarins inhibited inflammatory factor secretion in macrophages primed by LPS, in which compounds 4, 6, 7, 10, 17 showed the most pronounced change, which were comparable to dexamethasone. In summary, peel of C. grandis showed an anti-inflammatory effect and coumarin compounds were responsible for regulating inflammatory mediators and cytokines, which might provide a novel nutritional strategy for inflammatory diseases.
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Affiliation(s)
- Yun-Li Zhao
- Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology , Yunnan University , Kunming , Yunnan 650091 , People's Republic of China
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
| | - Xiong-Wu Yang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
| | - Bai-Fen Wu
- Yunnan University of Chinese Medicine , Kunming , Yunnan 650500 , People's Republic of China
| | - Jian-Hua Shang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
| | - Ya-Ping Liu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
| | - Xiao-Dong Luo
- Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology , Yunnan University , Kunming , Yunnan 650091 , People's Republic of China
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
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Ko EY, Heo SJ, Cho SH, Lee W, Kim SY, Yang HW, Ahn G, Cha SH, Kwon SH, Jeong MS, Lee KP, Jeon YJ, Kim KN. 3‑Bromo‑5‑(ethoxymethyl)‑1,2‑benzenediol inhibits LPS-induced pro-inflammatory responses by preventing ROS production and downregulating NF-κB in vitro and in a zebrafish model. Int Immunopharmacol 2019; 67:98-105. [DOI: 10.1016/j.intimp.2018.11.021] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 11/12/2018] [Accepted: 11/14/2018] [Indexed: 12/15/2022]
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Prevention of Peritendinous Adhesion Formation After the Flexor Tendon Surgery in Rabbits: A Comparative Study Between Use of Local Interferon-α, Interferon-β, and 5-Fluorouracil. Ann Plast Surg 2018; 80:171-175. [PMID: 28671883 DOI: 10.1097/sap.0000000000001169] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Peritendinous adhesion is the most common complication after tendon surgery, particularly in zone II of the hand. Prevention of inflammation around the tendon, which develops after trauma and surgery, can decrease the tendon adhesion formation. This study compares the effect of some anti-inflammatory cytokines with 5-fluorouracil (5-FU) on the tensile strength and in prevention of peritendinous adhesion formation. METHODS Sixteen rabbits were allocated equally into 4 groups. Tendons of the index and ring fingers in zone II of the right hind paw were cut in all animals and then repaired. Interferon (IFN)-α in group 1, 5-FU in group 2, normal saline in group 3, and IFN-β in group 4 were locally applied to the repaired sites. Three weeks later, tensometric and histopathologic evaluations were performed. RESULTS The force required for removing the tendon from the sheath was not different between the groups (P = 0.130), but the time required for removal was significantly shorter in 5-FU group (P = 0.049). The strength of repair was not different between the groups in terms of force and time needed for rupture (P = 0.11 and 0.67, respectively). In histopathologic examination, normal architecture of the tendon and peritendon environment was less disturbed in the IFN groups, especially in IFN-β specimens. CONCLUSIONS Local application of 5-FU significantly reduced peritendinous adhesion. Local IFN-α and IFN-β had no significant effect on the prevention of peritendinous adhesion formation. The strength of the repair was not affected by these cytokines and 5-FU.
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Rosas RF, Emer AA, Batisti AP, Ludtke DD, Turnes BL, Bobinski F, Cidral-Filho FJ, Martins DF. Far infrared-emitting ceramics decrease Freund's adjuvant-induced inflammatory hyperalgesia in mice through cytokine modulation and activation of peripheral inhibitory neuroreceptors. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2018; 16:396-403. [PMID: 30139655 DOI: 10.1016/j.joim.2018.08.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 06/22/2018] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The present study aimed to evaluate the analgesic and anti-inflammatory effects of far infrared-emitting ceramics (cFIRs) in a model of persistent inflammatory hyperalgesia and to elucidate the possible mechanisms of these effects. METHODS Mice were injected with complete Freund's adjuvant (CFA) and treated with cFIRs via placement on a pad impregnated with cFIRs on the bottom of the housing unit for different periods of time. Mice underwent mechanical hyperalgesia and edema assessments, and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-10 levels were measured. Twenty-four hours after CFA injection and 30 min before cFIR treatment, mice were pretreated with a nonselective adenosinergic antagonist, caffeine, the selective adenosine receptor A1 antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), the selective cannabinoid receptor type 1 antagonist, AM281, the selective cannabinoid receptor type 2 antagonist, AM630, or the nonselective opioid receptor antagonist, naloxone, and mechanical hyperalgesia was assessed. RESULTS cFIRs statistically (P < 0.05) decreased CFA-induced mechanical hyperalgesia ((82.86 ± 5.21)% in control group vs (56.67 ± 9.54)% in cFIR group) and edema ((1699.0 ± 77.8) μm in control group vs (988.7 ± 107.6) μm in cFIR group). cFIRs statistically (P < 0.05) reduced TNF-α ((0.478 ± 0.072) pg/mg of protein in control group vs (0.273 ± 0.055) pg/mg of protein in cFIR group) and IL-1β ((95.81 ± 3.95) pg/mg of protein in control group vs (80.61 ± 4.71) pg/mg of protein in cFIR group) levels and statistically (P < 0.05) increased IL-10 ((18.32 ± 0.78) pg/mg of protein in control group vs (25.89 ± 1.23) pg/mg of protein in cFIR group) levels in post-CFA-injected paws. Peripheral pre-administration of inhibitory neuroreceptor antagonists (caffeine, DPCPX, AM281, AM630 and naloxone) prevented the analgesic effects of cFIRs (P < 0.05). CONCLUSION These data provide additional support for the use of cFIRs in the treatment of painful inflammatory conditions and contribute to our understanding of the neurobiological mechanisms of the therapeutic effects of cFIRs.
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Affiliation(s)
- Ralph Fernando Rosas
- Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil; Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil
| | - Aline Armiliato Emer
- Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil; Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil
| | - Ana Paula Batisti
- Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil; Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil
| | - Daniela Dero Ludtke
- Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil; Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil
| | - Bruna Lenfers Turnes
- Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil; Laboratory of Bioenergetics and Oxidative Stress (LABOX), Federal University of Santa Catarina, Florianópolis 88049-000, Santa Catarina, Brazil
| | - Franciane Bobinski
- Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil; Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil
| | - Francisco José Cidral-Filho
- Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil; Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil
| | - Daniel Fernandes Martins
- Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil; Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça 88137-272, Santa Catarina, Brazil.
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Ahmad W, Jantan I, Kumolosasi E, Haque MA, Bukhari SNA. Immunomodulatory effects of Tinospora crispa extract and its major compounds on the immune functions of RAW 264.7 macrophages. Int Immunopharmacol 2018; 60:141-151. [DOI: 10.1016/j.intimp.2018.04.046] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 04/25/2018] [Accepted: 04/27/2018] [Indexed: 11/26/2022]
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Plastina P, Apriantini A, Meijerink J, Witkamp R, Gabriele B, Fazio A. In Vitro Anti-Inflammatory and Radical Scavenging Properties of Chinotto ( Citrus myrtifolia Raf.) Essential Oils. Nutrients 2018; 10:nu10060783. [PMID: 29912150 PMCID: PMC6024861 DOI: 10.3390/nu10060783] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 06/08/2018] [Accepted: 06/15/2018] [Indexed: 01/07/2023] Open
Abstract
Chinotto (Citrus myrtifolia Raf.) is a widely diffused plant native from China and its fruits have a wide-spread use in confectionary and drinks. Remarkably, only little has been reported thus far on its bioactive properties, in contrast to those of the taxonomically related bergamot (Citrus bergamia Risso). The present study aimed to investigate potential in vitro anti-inflammatory and radical scavenging properties of chinotto essential oils (CEOs) and to establish to what extent their composition and bioactivities are dependent on maturation. Essential oil from half ripe chinotto (CEO2) reduced the production of nitric oxide (NO) and the expression of inflammatory genes, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6), and chemokine monocyte chemotactic protein-1 (MCP-1) by lipopolysaccharide (LPS)-stimulated RAW264,7 macrophages. Limonene, linalool, linalyl acetate, and γ-terpinene were found to be the main components in CEO2. Moreover, CEO2 showed high radical scavenging activity measured as Trolox equivalents (TE) against both 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS). These findings show that chinotto essential oil represents a valuable part of this fruit and warrants further in vivo studies to validate its anti-inflammatory potential.
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Affiliation(s)
- Pierluigi Plastina
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy.
| | - Astari Apriantini
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy.
| | - Jocelijn Meijerink
- Division of Human Nutrition, Wageningen University, 6700 AA Wageningen, The Netherlands.
| | - Renger Witkamp
- Division of Human Nutrition, Wageningen University, 6700 AA Wageningen, The Netherlands.
| | - Bartolo Gabriele
- Department of Chemistry and Chemical Technologies, University of Calabria, 87036 Arcavacata di Rende (CS), Italy.
| | - Alessia Fazio
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy.
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Lee SA, Moon SM, Han SH, Hwang EJ, Hong JH, Park BR, Choi MS, Ahn H, Kim JS, Kim HJ, Chun HS, Kim DK, Kim CS. In Vivo and In Vitro Anti-Inflammatory Effects of Aqueous Extract of Anthriscus sylvestris Leaves. J Med Food 2018; 21:585-595. [DOI: 10.1089/jmf.2017.4089] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Affiliation(s)
- Seul Ah Lee
- Department of Oral Biochemistry, College of Dentistry, Chosun University, Gwangju, Korea
| | - Sung-Min Moon
- Department of Oral Biology Research Institute, College of Dentistry, Chosun University, Gwangju, Korea
- CStech Research Institute, Gwangju, Korea
| | | | - Eun Ju Hwang
- Department of Oral Biochemistry, College of Dentistry, Chosun University, Gwangju, Korea
| | - Joon Ho Hong
- Nano Bio Research Center, Jeonnam Bioindustry Foundation, Jang Seong, Jeollanam-do, Korea
| | - Bo-Ram Park
- Department of Dental Hygiene, Chodang University, Muan, Muan-eup, Korea
| | - Mi Suk Choi
- Department of Dental Hygiene, Chodang University, Muan, Muan-eup, Korea
| | - Hoon Ahn
- Department of Dental Hygiene, Chodang University, Muan, Muan-eup, Korea
| | - Jae-Sung Kim
- Department of Oral Biology Research Institute, College of Dentistry, Chosun University, Gwangju, Korea
| | - Heung-Joong Kim
- Department of Oral Biology Research Institute, College of Dentistry, Chosun University, Gwangju, Korea
| | - Hong Sung Chun
- Department of Biomedical Science, Chosun University, Gwangju, Korea
| | - Do Kyung Kim
- Department of Oral Biology Research Institute, College of Dentistry, Chosun University, Gwangju, Korea
| | - Chun Sung Kim
- Department of Oral Biochemistry, College of Dentistry, Chosun University, Gwangju, Korea
- Department of Oral Biology Research Institute, College of Dentistry, Chosun University, Gwangju, Korea
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Moon SM, Lee SA, Hong JH, Kim JS, Kim DK, Kim CS. Oleamide suppresses inflammatory responses in LPS-induced RAW264.7 murine macrophages and alleviates paw edema in a carrageenan-induced inflammatory rat model. Int Immunopharmacol 2018; 56:179-185. [DOI: 10.1016/j.intimp.2018.01.032] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 01/18/2018] [Accepted: 01/22/2018] [Indexed: 02/07/2023]
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Efficient role of IgH 3' regulatory region deficient B-cells in the development of oil granulomas. Oncotarget 2018; 7:38741-38749. [PMID: 27231852 PMCID: PMC5122425 DOI: 10.18632/oncotarget.9588] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Accepted: 04/29/2016] [Indexed: 01/18/2023] Open
Abstract
Functional B-cells are essential for the formation of oil granulomas. The IgH 3′ regulatory region (3′RR) activates important check-points during B-cell maturation. We investigated if 3′RR-deficient B-cells remain efficient to develop oil granulomas in response to pristine. B-cells expressing an IgH 3′RR-deficient allele were similarly recruited to wild type allele expressing B-cells in the granuloma. No differences were observed between 3′RR-deficient mice and control mice for granuloma numbers, cellular composition and ability to express mRNA transcripts for several pro- and anti-inflammatory cytokines. Altogether these results suggest a normal role for 3′RR-deficient B-cells in the development of an acute B-cell-mediated inflammatory response.
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Sophora subprosrate polysaccharide inhibited cytokine/chemokine secretion via suppression of histone acetylation modification and NF-κb activation in PCV2 infected swine alveolar macrophage. Int J Biol Macromol 2017; 104:900-908. [DOI: 10.1016/j.ijbiomac.2017.06.102] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 06/17/2017] [Accepted: 06/25/2017] [Indexed: 11/18/2022]
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Kim EY, Moudgil KD. Immunomodulation of autoimmune arthritis by pro-inflammatory cytokines. Cytokine 2017; 98:87-96. [PMID: 28438552 PMCID: PMC5581685 DOI: 10.1016/j.cyto.2017.04.012] [Citation(s) in RCA: 113] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 04/09/2017] [Accepted: 04/10/2017] [Indexed: 12/18/2022]
Abstract
Pro-inflammatory cytokines promote autoimmune inflammation and tissue damage, while anti-inflammatory cytokines help resolve inflammation and facilitate tissue repair. Over the past few decades, this general feature of cytokine-mediated events has offered a broad framework to comprehend the pathogenesis of autoimmune and other immune-mediated diseases, and to successfully develop therapeutic approaches for diseases such as rheumatoid arthritis (RA). Anti-tumor necrosis factor-α (TNF-α) therapy is a testimony in support of this endeavor. However, many patients with RA fail to respond to this or other biologics, and some patients may suffer unexpected aggravation of arthritic inflammation or other autoimmune effects. These observations combined with rapid advancements in immunology in regard to newer cytokines and T cell subsets have enforced a re-evaluation of the perceived pathogenic attribute of the pro-inflammatory cytokines. Studies conducted by others and us in experimental models of arthritis involving direct administration of IFN-γ or TNF-α; in vivo neutralization of the cytokine; the use of animals deficient in the cytokine or its receptor; and the impact of the cytokine or anti-cytokine therapy on defined T cell subsets have revealed paradoxical anti-inflammatory and immunoregulatory attributes of these two cytokines. Similar studies in other models of autoimmunity as well as limited studies in arthritis patients have also unveiled the disease-protective effects of these pro-inflammatory cytokines. A major mechanism in this regard is the altered balance between the pathogenic T helper 17 (Th17) and protective T regulatory (Treg) cells in favor of the latter. However, it is essential to consider that this aspect of the pro-inflammatory cytokines is context-dependent such that the dose and timing of intervention, the experimental model of the disease under study, and the differences in individual responsiveness can influence the final outcomes. Nevertheless, the realization that pro-inflammatory cytokines can also be immunoregulatory offers a new perspective in fully understanding the pathogenesis of autoimmune diseases and in designing better therapies for controlling them.
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Affiliation(s)
- Eugene Y Kim
- Department of Pharmaceutical Sciences, School of Pharmacy, Washington State University, Spokane, WA, USA
| | - Kamal D Moudgil
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Division of Rheumatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
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Liu F, Zhang X, Ling P, Liao J, Zhao M, Mei L, Shao H, Jiang P, Song Z, Chen Q, Wang F. Immunomodulatory effects of xanthan gum in LPS-stimulated RAW 264.7 macrophages. Carbohydr Polym 2017; 169:65-74. [DOI: 10.1016/j.carbpol.2017.04.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2016] [Revised: 02/03/2017] [Accepted: 04/01/2017] [Indexed: 01/14/2023]
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Aqueous extract of Codium fragile suppressed inflammatory responses in lipopolysaccharide-stimulated RAW264.7 cells and carrageenan-induced rats. Biomed Pharmacother 2017; 93:1055-1064. [PMID: 28738499 DOI: 10.1016/j.biopha.2017.07.026] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 06/28/2017] [Accepted: 07/06/2017] [Indexed: 12/18/2022] Open
Abstract
Codium fragile (Suringar) Hariot has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria and has been shown to have various biological effects. In this study, we evaluated the anti-inflammatory effects of aqueous extract of C. fragile (AECF) using in vitro and in vivo models. Nitric oxide (NO), prostaglandin E2 (PGE2), inflammatory-related mRNAs, and proteins were determined using the Griess assay, enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and western blotting, respectively. Our results indicate that pretreatment of cells with AECF (50, 100 and 200μg/mL) significantly inhibited LPS-induced secretion of NO and PGE2 in RAW264.7 cells without cytotoxicity. We also found that AECF (100 and 200μg/mL) inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 expression in a dose-dependent manner. Additionally, pretreatment of cells with AECF (100 and 200μg/mL) inhibited LPS-induced production of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. It also prevented the nuclear translocation of nuclear factor (NF)-κB by suppressing the phosphorylation and degradation of inhibitor of NF-κB (IκB)-α. Furthermore, AECF (100 and 200μg/mL) inhibited the phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. In addition, orally administered 50, 100, and 200mg/kg body weight of AECF dose-dependently suppressed carrageenan-induced rat paw edema thickness by 6%, 31%, and 50% respectively, after 4h. Furthermore, the anti-inflammatory effect was comparable to that observed in animals treated with the standard drug diclofenac sodium (56%) in vivo. Collectively, our results suggest that AECF exerts potential anti-inflammatory effects by suppressing NF-κB activation and MAPKs pathways in vitro, as well as inhibiting carrageenan-induced rat paw edema thickness in vivo. These findings indicate that AECF could be further developed as an anti-inflammatory drug.
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40
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Yu S, Zhou X, Li F, Xu C, Zheng F, Li J, Zhao H, Dai Y, Liu S, Feng Y. Microbial transformation of ginsenoside Rb1, Re and Rg1 and its contribution to the improved anti-inflammatory activity of ginseng. Sci Rep 2017; 7:138. [PMID: 28273939 PMCID: PMC5428039 DOI: 10.1038/s41598-017-00262-0] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Accepted: 02/16/2017] [Indexed: 11/09/2022] Open
Abstract
Microbial transformation of ginsenosides to increase its pharmaceutical effect is gaining increasing attention in recent years. In this study, Cellulosimicrobium sp. TH-20, which was isolated from soil samples on which ginseng grown, exhibited effective ginsenoside-transforming activity. After protopanaxadiol (PPD)-type ginsenoside (Rb1) and protopanaxatriol (PPT)-type ginsenosides (Re and Rg1) were fed to C. sp. TH20, a total of 12 metabolites, including 6 new intermediate metabolites, were identified. Stepwise deglycosylation and dehydrogenation on the feeding precursors have been observed. The final products were confirmed to be rare ginsenosides Rd, GypXVII, Rg2 and PPT after 96 h transformation with 38–96% yields. The four products showed improved anti-inflammatory activities by using lipopolysaccharide (LPS)-induced murine RAW 264.7 macrophages and the xylene-induced acute inflammatory model of mouse ear edema. The results indicated that they could dramatically attenuate the production of TNF-α more effectively than the precursors. Our study would provide an example of a unique and powerful microbial cell factory for efficiently converting both PPD-type and PPT-type ginsenosides to rare natural products, which extends the drug candidates as novel anti-inflammatory remedies.
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Affiliation(s)
- Shanshan Yu
- State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China. .,Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China.
| | - Xiaoli Zhou
- College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, China
| | - Fan Li
- School of Life Sciences, Northeast Normal University, Changchun, 130024, China
| | - Chunchun Xu
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - Fei Zheng
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - Jing Li
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - Huanxi Zhao
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - Yulin Dai
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - Shuying Liu
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - Yan Feng
- State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
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BenSaad LA, Kim KH, Quah CC, Kim WR, Shahimi M. Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 17:47. [PMID: 28088220 PMCID: PMC5237561 DOI: 10.1186/s12906-017-1555-0] [Citation(s) in RCA: 263] [Impact Index Per Article: 32.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 01/05/2017] [Indexed: 12/21/2022]
Abstract
Background Punica granatum (pomegranate), an edible fruit originating in the Middle East, has been used as a traditional medicine for treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of isolated compounds from the ethyl acetate (EtOAc) fraction of P. granatum by determination of their inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX-2) release from RAW264.7 cells. Methods The compounds ellagic acid, gallic acid and punicalagin A&B were isolated from EtOAc by high performance liquid chromatography (HPLC) and further identified by mass spectrometry (MS). The inhibitory effect of ellagic acid, gallic acid and punicalagin A&B were evaluated on the production of LPS-induced NO by Griess reagent, PGE-2 and IL-6 by immunoassay kit and prostaglandin E2 competitive ELISA kit, and COX-2 by Western blotting. Results Ellagic acid, gallic acid and punicalagin A&B potentially inhibited LPS-induced NO, PGE-2 and IL-6 production. Conclusion The results indicate that ellagic acid, gallic acid and punicalagin may be the compounds responsible for the anti-inflammatory potential of P. granatum.
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Nguyen Thi Dieu T, Pham Nhat A, Craig TJ, Duong-Quy S. Clinical characteristics and cytokine changes in children with pneumonia requiring mechanical ventilation. J Int Med Res 2017; 45:1805-1817. [PMID: 28703632 PMCID: PMC5805188 DOI: 10.1177/0300060516672766] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective To assess clinical characteristics and cytokine levels in children with
severe pneumonia who required ventilatory support. Methods In this prospective, descriptive, cross-sectional study, blood and
endotracheal fluid samples were obtained from patients with severe
pneumonia, aged <5 years, within 24 h following intubation. Blood samples
were also obtained from age-matched healthy controls. Cytokine levels were
investigated using flow cytometry-assisted immunoassay. Results Forty-five patients with severe pneumonia requiring mechanical ventilation
(aged 10 ± 5 months) and 35 healthy age-matched controls were included.
Patients with severe pneumonia had significantly increased serum interleukin
(IL)-6, IL-8, and granulocyte/macrophage colony-stimulating factor
concentrations compared with controls (80.84 pg/ml versus 2.06 pg/ml,
90.03 pg/ml versus 6.62 pg/ml, and 115.58 pg/ml versus 11.47 pg/ml,
respectively). In the severe pneumonia group, serum IL-10 levels were
significantly higher in patients aged <6 months versus those aged 6–12
months. Age-group differences in serum cytokine levels did not correspond to
age-group differences in endotracheal-fluid cytokine levels. Serum IL-6
levels were significantly higher in patients who subsequently died versus
those who survived (267.12 pg/ml versus 20.75 pg/ml, respectively). Conclusion High IL-6 concentrations were associated with mortality in patients <5
years of age with severe pneumonia requiring mechanical ventilation.
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Affiliation(s)
- Thuy Nguyen Thi Dieu
- 1 Department of Immunology, Allergology and Rheumatology, National Hospital of Paediatrics, Hanoi Medical University, Hanoi, Vietnam
| | - An Pham Nhat
- 1 Department of Immunology, Allergology and Rheumatology, National Hospital of Paediatrics, Hanoi Medical University, Hanoi, Vietnam
| | - Timothy J Craig
- 2 Department of Pulmonary, Allergy and Critical Care Medicine, Penn State University, Hershey, PA, USA
| | - Sy Duong-Quy
- 2 Department of Pulmonary, Allergy and Critical Care Medicine, Penn State University, Hershey, PA, USA.,3 Department of Respiratory Diseases, Bio-Medical Research Centre, Lam Dong Medical College, Dalat, Vietnam.,4 Department of Respiratory and Lung Functional Exploration, Cochin Hospital, Paris Descartes University, Paris, France
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Sandhiutami NMD, Moordiani M, Laksmitawati DR, Fauziah N, Maesaroh M, Widowati W. In vitro assesment of anti-inflammatory activities of coumarin and Indonesian cassia extract in RAW264.7 murine macrophage cell line. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2017; 20:99-106. [PMID: 28133531 PMCID: PMC5243982 DOI: 10.22038/ijbms.2017.8102] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Accepted: 10/18/2016] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Inflammation is an immune response toward injuries. Although inflammation is healing response, but in some condition it will lead to chronic disease such as rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, Alzheimer's and various cancer. Indonesian cassia (Cinnamomum burmannil C. Nees & T. Ness) known to contain coumarin, is widely used for alternative medicine especially as an anti-inflammatory. This study was conducted to determine the anti-inflammatory properties of coumarin and Indonesian cassia extract (ICE) in LPS-induced RAW264.7 cell line. MATERIALS AND METHODS The cytotoxic assay of coumarin and ICE against RAW264.7 cells was conducted using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium). The anti-inflammatory potential was determined using LPS-induced RAW 267.4 macrophages cells to measure inhibitory activity of compound and ISEon production of nitric oxide (NO), prostaglandin E2 (PGE2), and also cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and TNF-α. RESULTS Coumarin 10 µM and ICE 10 µg/ml were nontoxic to the RAW264.7 cells. Both of coumarin and ICE were capable to reduce the PGE2, TNF-α, NO, IL-6, and IL-β level in LPS-induced RAW264.7 cells. Coumarin had higher activity to decrease PGE2 and TNF-α, whilst ICE had higher activity to inhibit NO, IL-6, and IL-β levels. CONCLUSION Coumarin and ICE possess anti-inflammatory properties through inhibition of PGE2 and NO along with pro-inflammatory cytokines TNF-α, IL-6, IL-1β production.
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Affiliation(s)
- Ni Made Dwi Sandhiutami
- Faculty of Pharmacy, University of Pancasila, Jl. Srenseng Sawah, Jagakarsa, Jakarta 12640, Indonesia
| | - Moordiani Moordiani
- Faculty of Pharmacy, University of Pancasila, Jl. Srenseng Sawah, Jagakarsa, Jakarta 12640, Indonesia
| | - Dian Ratih Laksmitawati
- Faculty of Pharmacy, University of Pancasila, Jl. Srenseng Sawah, Jagakarsa, Jakarta 12640, Indonesia
| | - Nurul Fauziah
- Bimolecular and Biomedical Research Center, Aretha Medika Utama, Jl. Babakan Jeruk 2 no 9, Bandung 40163, Indonesia
| | - Maesaroh Maesaroh
- Bimolecular and Biomedical Research Center, Aretha Medika Utama, Jl. Babakan Jeruk 2 no 9, Bandung 40163, Indonesia
| | - Wahyu Widowati
- Medical Research Center, Faculty of Medicine, Maranatha Christian University, Jl. Prof. drg. Suria Sumantri no 65 Bandung 40164, Indonesia
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Liu D, Zhou JL, Hong F, Zhang YQ. Lung inflammation caused by long-term exposure to titanium dioxide in mice involving in NF-κB signaling pathway. J Biomed Mater Res A 2016; 105:720-727. [DOI: 10.1002/jbm.a.35945] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 10/06/2016] [Accepted: 10/19/2016] [Indexed: 12/29/2022]
Affiliation(s)
- Dong Liu
- Department of Applied Biology, School of Basic Medical and Biological Sciences; Soochow University; RM702-2303, Renai Road No. 199 Dushuhu Higher Edu. Town Suzhou 215123 People's Republic of China
| | - Jie-Lu Zhou
- Department of Scientific and Educational Affairs; Suzhou Kowloon Hospital Affiliated with Shanghai Jiao Tong University School of Medicine; Suzhou 215021 People's Republic of China
| | - Fashui Hong
- Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection; Huaiyin Normal University; Huaian 223300 China
- Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake; Huaiyin Normal University; Huaian 223300 China
| | - Yu-Qing Zhang
- Department of Applied Biology, School of Basic Medical and Biological Sciences; Soochow University; RM702-2303, Renai Road No. 199 Dushuhu Higher Edu. Town Suzhou 215123 People's Republic of China
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45
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Kim AR, Lee B, Joung EJ, Gwon WG, Utsuki T, Kim NG, Kim HR. 6,6′-Bieckol suppresses inflammatory responses by down-regulating nuclear factor-κB activation via Akt, JNK, and p38 MAPK in LPS-stimulated microglial cells. Immunopharmacol Immunotoxicol 2016; 38:244-52. [DOI: 10.3109/08923973.2016.1173060] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Liu Q, Wang Z, Liu LL, Li P, Liu EH. Discovery of anti-inflammatory components from Guge Fengtong tablet based on inflammatory markers and exploration of its molecular mechanism. RSC Adv 2016. [DOI: 10.1039/c6ra17737a] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
In this work, we discovered GGFTT and its bioactive combinatorial components (10C) could significantly decrease the production of TNF-α, IL-1β, IL-6. 10C exert comparable anti-inflammatory effect through NF-κB and MAPKs signaling pathways as GGFTT.
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Affiliation(s)
- Qun Liu
- State Key Laboratory of Natural Medicines
- China Pharmaceutical University
- Nanjing 210009
- China
| | - Zhen Wang
- State Key Laboratory of Natural Medicines
- China Pharmaceutical University
- Nanjing 210009
- China
| | - Le-Le Liu
- State Key Laboratory of Natural Medicines
- China Pharmaceutical University
- Nanjing 210009
- China
| | - Ping Li
- State Key Laboratory of Natural Medicines
- China Pharmaceutical University
- Nanjing 210009
- China
| | - E-Hu Liu
- State Key Laboratory of Natural Medicines
- China Pharmaceutical University
- Nanjing 210009
- China
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47
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Ribeiro D, Freitas M, Tomé SM, Silva AMS, Laufer S, Lima JLFC, Fernandes E. Flavonoids inhibit COX-1 and COX-2 enzymes and cytokine/chemokine production in human whole blood. Inflammation 2015; 38:858-70. [PMID: 25139581 DOI: 10.1007/s10753-014-9995-x] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Cyclooxygenase 2 (COX-2) and the production of cytokines/chemokines are important targets for the modulation of the inflammatory response. Although a large variety of inhibitors of these pathways have been commercialized, some of those inhibitors present severe side effects, governing the search for new molecules, as alternative anti-inflammatory agents. This study was undertaken to study an hitherto not evaluated group of flavonoids, concerning its capacity to inhibit COX-1 and COX-2 enzymes, as well as to inhibit the production of the cytokines and a chemokine, in a complex matrix involved in the systemic inflammatory process, the blood, aiming the establishment of a structure-activity relationship. The results obtained reveal promising flavonoids for the modulation of the inflammatory process, namely the ones presenting a catechol group in B ring, as some flavonoids were able to simultaneously inhibit the production of inflammatory prostaglandin E2 and pro-inflammatory cytokines.
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Affiliation(s)
- Daniela Ribeiro
- REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira n 228, 4050-313, Porto, Portugal
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48
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Yu DK, Lee B, Kwon M, Yoon N, Shin T, Kim NG, Choi JS, Kim HR. Phlorofucofuroeckol B suppresses inflammatory responses by down-regulating nuclear factor κB activation via Akt, ERK, and JNK in LPS-stimulated microglial cells. Int Immunopharmacol 2015; 28:1068-75. [PMID: 26341413 DOI: 10.1016/j.intimp.2015.08.028] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 08/17/2015] [Accepted: 08/24/2015] [Indexed: 12/13/2022]
Abstract
Microglial activation has been implicated in many neurological disorders for its inflammatory and neurotrophic effects. In this study, we investigated the effects of phlorofucofuroeckol B (PFF-B) isolated from Ecklonia stolonifera, on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated microglia. PFF-B decreased secretion of pro-inflammatory cytokines including tumor necrosis factor α, interleukin (IL)-1β, and IL-6 and the expression of pro-inflammatory proteins such as cyclooxygenase-2 and inducible nitric oxide synthase in LPS-stimulated BV-2 cells. Profoundly, PFF-B inhibited activation of nuclear factor kappaB (NF-κB) by preventing the degradation of inhibitor κB-α (IκB-α), which led to prevent the nuclear translocation of p65 NF-κB subunit. Moreover, PFF-B inhibited the phosphorylation of Akt, ERK, and JNK. These results indicate that the anti-inflammatory effect of PFF-B on LPS-stimulated microglial cells is mainly regulated by the inhibition of IκB-α/NF-κB and Akt/ERK/JNK pathways. Our study suggests that PFF-B can be considered as a therapeutic agent against neuroinflammation by inhibiting microglial activation.
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Affiliation(s)
- Dong-Kyung Yu
- Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, South Korea
| | - Bonggi Lee
- Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, South Korea
| | - Misung Kwon
- Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, South Korea
| | - Nayoung Yoon
- Food and Safety Research Division, National Fisheries Research and Development Institute, Gijang-gun, Busan 619-705, South Korea
| | - Taisun Shin
- Division of Food and Nutrition, Chonnam National University, Buk-gu, Gwangju 500-757, South Korea
| | - Nam-Gil Kim
- Department of Marine Biology, Gyeongsang National University, Tongyoung 650-757, South Korea
| | - Jae-Sue Choi
- Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, South Korea
| | - Hyeung-Rak Kim
- Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, South Korea.
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Tirado-Sánchez A, Bonifaz A, Ponce-Olivera R. Elevated interleukin-33 and soluble ST2 levels in the sera of patients with pemphigus vulgaris: correlation with clinical and immunological parameters during follow-up. Br J Dermatol 2015; 173:818-20. [DOI: 10.1111/bjd.13716] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- A. Tirado-Sánchez
- Servicio de Dermatología; Hospital General de México; Dr. Balmis 148, Col. Doctores Deleg. Cuauhtemoc C.P. 06726 México
- Dermatology Department; Instituto Mexicano del Seguro Social; Av. Paseo de la Reforma 476 Planta Baja Cuauhtémoc, Juárez Ciudad de México 06600 México
| | - A. Bonifaz
- Servicio de Dermatología; Hospital General de México; Dr. Balmis 148, Col. Doctores Deleg. Cuauhtemoc C.P. 06726 México
| | - R.M. Ponce-Olivera
- Servicio de Dermatología; Hospital General de México; Dr. Balmis 148, Col. Doctores Deleg. Cuauhtemoc C.P. 06726 México
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The anti-inflammatory effects of palmitoylethanolamide (PEA) on endotoxin-induced uveitis in rats. Eur J Pharmacol 2015; 761:28-35. [PMID: 25934566 DOI: 10.1016/j.ejphar.2015.04.025] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Revised: 04/15/2015] [Accepted: 04/20/2015] [Indexed: 01/09/2023]
Abstract
The aim of this study was to investigate the effects of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs), in rats subjected to endotoxin-induced uveitis (EIU). EIU was induced in male rats by a single footpad injection of 200μg lipopolysaccharide (LPS). PEA was administered intraperitoneally at 1h before and 7h after injection of LPS. Another group of animals was treated with vehicle. Dexamethasone (DEX) was administered as a positive control. Rats were sacrificed 16h after injection and the eyes tissues were collected for histology, immunohistochemical and western blot analyses. The histological evaluation of the iris-ciliary body showed an increase of neutrophilic infiltration and nuclear modification of vessel of endothelial cells. PEA treatment decreased the inflammatory cell infiltration and improved histological damage of eye tissues. In addition, PEA treatment reduced pro-inflammatory tumor necrosis factor (TNF-α) levels, protein extravasion and lipid peroxidation. Immunohistochemical analysis for intracellular adhesion molecule (ICAM)-1 and nitrotyrosine showed a positive staining from LPS-injected rats. The degree of staining for ICAM-1 and nitrotyrosine was significantly reduced in eye sections from LPS-injected rats treated with PEA. In addition, an increase of inducible nitric oxide synthase (iNOS) and nuclear factor (NF-κB) was also evaluated in inflammed ocular tissues by western blot. PEA strongly inhibited iNOS expression and nuclear NF-κB translocation. Thus, in this study we demonstrated that PEA reduces the degree of ocular inflammation in a rat model of EIU.
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