May BDNF Be Implicated in the Exercise-Mediated Regulation of Inflammation? Critical Review and Synthesis of Evidence

Introduction: Exercise attenuates inflammation and enhances levels of brain-derived neurotrophic factor (BDNF). Exercise also enhances parasympathetic tone, although its role in activating the cholinergic anti-inflammatory pathway is unclear. The physiological pathways of exercise’s effect on inflammation are obscure. Aims: To critically review the evidence on the role of BDNF in the anti-inflammatory effects of exercise and its potential involvement in the cholinergic anti-inflammatory pathway. Methods: Critical literature review of studies published in MEDLINE, PubMed, CINAHL, Embase, and Cochrane databases. Results: BDNF is critically involved in the bidirectional signaling between immune and neurosensory cells and in the regulation of parasympathetic system responses. BDNF is also intricately involved in the inflammatory response: inflammation induces BDNF production, and, in turn, BDNF exerts pro- and/or anti-inflammatory effects. Although exercise modulates BDNF and its receptors in lymphocytes, data on BDNF’s immunoregulatory/anti-inflammatory effects in relation to exercise are scarce. Moreover, BDNF increases cholinergic activity and is modulated by parasympathetic system activation. However, its involvement in the cholinergic anti-inflammatory pathway has not been investigated. Conclusion: Converging lines of evidence implicate BDNF in exercise-mediated regulation of inflammation; however, data are insufficient to draw concrete conclusions. We suggest that there is a need to investigate BDNF as a potential modulator/mediator of the anti-inflammatory effects of exercise and of the cholinergic anti-inflammatory pathway during exercise. Such research would have implications for a wide range of inflammatory diseases and for planning targeted exercise protocols.

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Heparin and proteoglycans as anti-inflammatory drugs

Hämostaseologie ◽

10.1055/s-0038-1656639 ◽

1996 ◽

Vol 16 (01) ◽

pp. 56-59

Author(s):

D. J. Tyrrell ◽

C. P. Page

Keyword(s):

Inflammatory Diseases ◽

Therapeutic Applications ◽

Wide Range ◽

Inflammatory Drugs ◽

Anti Inflammatory

SummaryEvidence continues to accumulate that the pleiotropic nature of heparin (beyond its anticoagulant potency) includes anti-inflammatory activities at a number of levels. It is clear that drugs exploiting these anti-inflammatory activities of heparin may offer exciting new therapeutic applications to the treatment of a wide range of inflammatory diseases.

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The Role of α7nAChR-Mediated Cholinergic Anti-inflammatory Pathway in Immune Cells

Inflammation ◽

10.1007/s10753-020-01396-6 ◽

2021 ◽

Author(s):

Yi-jin Wu ◽

Li Wang ◽

Chao-fan Ji ◽

Shao-fei Gu ◽

Qin Yin ◽

...

Keyword(s):

Immune Cells ◽

Inflammatory Pathway ◽

Anti Inflammatory

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Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

Pharmaceuticals ◽

10.3390/ph14070692 ◽

2021 ◽

Vol 14 (7) ◽

pp. 692

Author(s):

Ryldene Marques Duarte da Cruz ◽

Francisco Jaime Bezerra Mendonça-Junior ◽

Natália Barbosa de Mélo ◽

Luciana Scotti ◽

Rodrigo Santos Aquino de Araújo ◽

...

Keyword(s):

Inflammatory Diseases ◽

Structural Characteristics ◽

Tiaprofenic Acid ◽

Inflammatory Activity ◽

Drug Candidates ◽

Biological Target ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Privileged Structures

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

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The role of the cholinergic anti‐inflammatory pathway in autoimmune rheumatic diseases

Scandinavian Journal of Immunology ◽

10.1111/sji.13092 ◽

2021 ◽

Author(s):

Jiaqi Lv ◽

Xiaoxiao Ji ◽

Zhen Li ◽

Huiqin Hao

Keyword(s):

Rheumatic Diseases ◽

Inflammatory Pathway ◽

Autoimmune Rheumatic Diseases ◽

Anti Inflammatory

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The role of celecoxib as a potential inhibitor in the treatment of inflammatory diseases - a review

Current Medicinal Chemistry ◽

10.2174/0929867328666210910125229 ◽

2021 ◽

Vol 28 ◽

Author(s):

Josiane Viana Cruz ◽

Joaquín María Campos Rosa ◽

Njogu Mark Kimani ◽

Silvana Giuliatti ◽

Cleydson Breno Rodrigues dos Santos

Keyword(s):

Side Effects ◽

Inflammatory Diseases ◽

Structural Basis ◽

Potential Inhibitor ◽

Cyclooxygenase 1 ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors

: This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from “coxibs”, celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.

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Disordered haematopoiesis and cardiovascular disease: a focus on myelopoiesis

Clinical Science ◽

10.1042/cs20180111 ◽

2018 ◽

Vol 132 (17) ◽

pp. 1889-1899 ◽

Cited By ~ 8

Author(s):

Dragana Dragoljevic ◽

Marit Westerterp ◽

Camilla Bertuzzo Veiga ◽

Prabhakara Nagareddy ◽

Andrew J. Murphy

Keyword(s):

Inflammatory Diseases ◽

Genetic Evidence ◽

Loss Of Function ◽

Atherosclerotic Vascular Disease ◽

Stem And Progenitor Cells ◽

Anti Inflammatory ◽

The Cantos ◽

Inflammatory Milieu ◽

Proliferative Advantage

Cardiovascular (CV) diseases (CVD) are primarily caused by atherosclerotic vascular disease. Atherogenesis is mainly driven by recruitment of leucocytes to the arterial wall, where macrophages contribute to both lipid retention as well as the inflammatory milieu within the vessel wall. Consequently, diseases which present with an enhanced abundance of circulating leucocytes, particularly monocytes, have also been documented to accelerate CVD. A host of metabolic and inflammatory diseases, such as obesity, diabetes, hypercholesteraemia, and rheumatoid arthritis (RA), have been shown to alter myelopoiesis to exacerbate atherosclerosis. Genetic evidence has emerged in humans with the discovery of clonal haematopoiesis of indeterminate potential (CHIP), resulting in a disordered haematopoietic system linked to accelerated atherogenesis. CHIP, caused by somatic mutations in haematopoietic stem and progenitor cells (HSPCs), consequently provide a proliferative advantage over native HSPCs and, in the case of Tet2 loss of function mutation, gives rise to inflammatory plaque macrophages (i.e. enhanced interleukin (IL)-1β production). Together with the recent findings of the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) trial that revealed blocking IL-1β using Canakinumab reduced CV events, these studies collectively have highlighted a pivotal role of IL-1β signalling in a population of people with atherosclerotic CVD. This review will explore how haematopoiesis is altered by risk-factors and inflammatory disorders that promote CVD. Further, we will discuss some of the recent genetic evidence of disordered haematopoiesis in relation to CVD though the association with CHIP and suggest that future studies should explore what initiates HSPC mutations, as well as how current anti-inflammatory agents affect CHIP-driven atherosclerosis.

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Application of Plant-Based Preparations in a Comprehensive Treatment of Inflammatory Periodontal Diseases

Ukraïnsʹkij žurnal medicini bìologìï ta sportu ◽

10.26693/jmbs06.05.038 ◽

2021 ◽

Vol 6 (5) ◽

pp. 38-44

Author(s):

O. D. Saliuk ◽

◽

P. H. Gerasimchuk ◽

L. O. Zaitsev ◽

I. I. Samoilenko ◽

...

Keyword(s):

Inflammatory Diseases ◽

Periodontal Diseases ◽

The Body ◽

Comprehensive Treatment ◽

Complex Treatment ◽

Medicinal Products ◽

Actual Problem ◽

Periodontal Tissues ◽

Wide Range ◽

Anti Inflammatory

In this article the review of foreign and domestic literary sources, which are devoted to the actual problem of modern dentistry – the treatment of inflammatory diseases of periodontal tissues: gingivitis and periodontitis are presented. The complex approach to their treatment involves the appointment of a significant amount of pharmacotherapeutic drugs. Therapeutic failures and iatrogenic complications have led to the fact that today the interests of doctors and population to medicinal products significantly increased. The purpose of the study is to analyze the data of scientific literature on the use of plant-based medicinal products for the treatment of periodontal inflammatory diseases over the past 10 years. Materials and methods. Comprehensive and systematic analysis of literature. Review and discussion. The analysis of information sources on the use of plant-based medicinal products in dentistry both independently and in the composition of medical and prophylactic means has established that the modern assortment of plant-based preparations in the pharmaceutical market of Ukraine to a certain extent is limited. The emergence of new plant-based species that have been tested in conditions of experimental pathology and require an evidence-based clinical base is noted. The composition of plant-based preparations used for the treatment of inflammatory periodontal diseases include vitamins, biologically active substances, glycosides, alkaloids, in connection with a wide range of action: antiseptic, anti-inflammatory, regenerating, hemostatic, antioxidative. The data on plant-based preparations that are most often used such as chamomile extracts, calendula, hypericum, plantain, kalanchoe, aloe, eucalyptus, milfoil, nettle, calamus and plant-based species are summarized. The medicinal agents considered are mainly recommended for local treatment of periodontal diseases in the form of dental care means, mouth rinse, gel, chewing gum, herbal liquer. It is known that the complex treatment of periodontal diseases includes a general influence on the body. The properties of green tea with its wide range of actions are investigated. With antioxidant properties, it can be a healthy alternative for controlling destructive changes in periodontal diseases. Attention is drawn to the proposed unique natural complex “Resverazin” due to a wide range of pharmacological action, low toxicity and relative safety. The drug produces antioxidant, anti-inflammatory, immune stimulating, vasodilative, neuroprotective action. Conclusion. Based on the literature analysis, it can be concluded that the accumulated experimental and clinical data on the therapeutic properties of plants prove perspective of their use in the complex treatment of inflammatory periodontal diseases. Future studies are mandatory for further confirmation of the effectiveness of these medicinal plants

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Abstract 035: Cholinergic Agonists Protect from the Development of Hypertension during Chronic Inflammatory Disease

Hypertension ◽

10.1161/hyp.64.suppl_1.035 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Keisa W Mathis

Keyword(s):

Protein Expression ◽

Lupus Erythematosus ◽

Inflammatory Diseases ◽

Autoimmune Disorder ◽

Chronic Inflammatory Disease ◽

Cholinergic Agonists ◽

Inflammatory Pathway ◽

Genetic Mouse Model ◽

Tnf Α ◽

Anti Inflammatory

Systemic lupus erythematosus (SLE) is an autoimmune disorder with prevalent hypertension. Previous studies using a genetic mouse model of SLE (NZBWF1) suggest chronic inflammation is an important contributor to SLE hypertension. A novel neuroimmune pathway involving the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) suppresses splenic cytokine release and reduces systemic inflammation upon stimulation. To test whether activation of this ‘cholinergic anti-inflammatory pathway’ at the level of the α7nAChR attenuates the development of hypertension during SLE, female SLE and control (NZW) mice were infused with nicotine hydrogen tartrate salt (2 mg/kg/day, SC) or saline for 7 days. Nicotine-treated SLE mice had lower splenic protein expression of TNF-α and IL-6 (normalized to β-actin) relative to saline-treated SLE mice (1.09±0.06 vs. 1.37±0.06 and 0.36±0.04 vs. 0.55±0.10; all p<0.05), suggesting efficacy of the therapy. Mean arterial pressure (MAP; mmHg) was increased in SLE mice compared to controls (140±4 vs. 114±2; p<0.001). Nicotine prevented the rise in MAP in SLE mice (129±4; p=0.022), but not controls (121±3). This protection from hypertension coincided with a 46±5% lower renal cortical TNF-α in nicotine-treated SLE mice compared to saline-treated SLE mice (0.39±0.04 vs. 0.73±0.18), which is important because it has been previously shown that renal TNF-α plays a mechanistic role in the development of hypertension during SLE. Because nicotine acts on both ganglionic and peripheral cholinergic receptors, in a subsequent study mice were administered the selective α7nAChR agonist, PNU-282987 (0.38 mg/kg/day, IP), or vehicle for 28 days. PNU-282987-treated SLE mice had lower splenic protein expression of TNF-α and IL-6 relative to saline-treated SLE mice (0.33±0.01 vs. 0.54±0.03 and 0.40±0.08 vs. 0.86±0.05; all p<0.05). MAP was increased in SLE mice compared to controls (138±2 vs. 122±5). PNU-282987 prevented the rise in MAP in SLE mice (128±4), but not controls (125±5). These data suggest the anti-inflammatory effects of cholinergic agonists may protect from SLE hypertension and that the cholinergic anti-inflammatory pathway may be an important target in hypertensive patients with chronic inflammatory diseases.

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The role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in Hirschsprung associated enterocolitis

10.21203/rs.3.rs-17106/v1 ◽

2020 ◽

Author(s):

Feng Chen ◽

Xiaoyu Wei ◽

Xiaohua Chen ◽

Lei Xiang ◽

Xinyao Meng ◽

...

Keyword(s):

Western Blotting ◽

Mrna Level ◽

Underlying Mechanism ◽

Mrna Levels ◽

Wild Type ◽

Inflammatory Pathway ◽

Anti Inflammatory ◽

Phosphorylated Stat3 ◽

Morphology Changes

Abstract Background To investigate the role and the underlying mechanism of the α7nAChR-mediated cholinergic anti-inflammatory pathway in the pathogenesis of Hirschsprung(HSCR) associated enterocolitis（HAEC）. Methods Experimental group:twenty-one-day-old Ednrb-/- mice were selected (n=10), with comparable-age wild type(Ednrb+/+) mice controls (n=10). Intestinal samples were collected. The experimental colons were divided into narrow and dilated segments according to morphology changes. The control colons were divided into distal and proximal segments.Colon HE staining was used to judge HAEC.Acetylcholine levels in colon was measured using enzyme-linked immunosorbent assays. Detected phosphorylated Jak2 (p-Jak2), Jak2, phosphorylated Stat3 (p-Stat3), Stat3, phosphorylated IκBα (p-IκBα) and IκBα were studied by Western blotting; mRNA levels of Jak2, Stat3, and IκBα were detected by RT-qPCR. Results Colon HE staining indicated that HAEC mainly occured in the dilated segments of HSCR mice (Ednrb-/- mice) (EDNRB-P).Acetylcholine content in EDNRB-P was significantly lower than that in the narrow segments (EDNRB-D) (P<0.05). Western blotting showed that the Jak2, p-Jak2, Stat3 and p-Stat3 levels in EDNRB-D were significantly higher than those in EDNRB-P (P<0.05). The p-IκBα and IκBα levels in EDNRB-P were significantly higher than those in EDNRB-D(P<0.05). The mRNA levels of Jak2 and Stat3 in EDNRB-D were higher than those in EDNRB-P, but the IκBα mRNA level was significantly lower than that in EDNRB-P (P<0.05). Conclusions During HAEC, the inflammation in the dilated segment was more severe ,while in the narrow segment there was no obvious inflammatory reaction and the content of acetylcholine was higher, which was associated with the α7nAChR-mediated cholinergic anti-inflammatory pathway.

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