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Background: The cholinergic anti-inflammatory pathway, positioned at the interface of the nervous and immune systems, is the efferent limb of the "inflammatory reflex" which mainly signals through the vagus nerve. As such, the brain can modulate peripheral inflammatory responses by the activation of vagal efferent fibers. Importantly, immune cells in the spleen express most cholinergic system components such as acetylcholine (ACh), choline acetyltransferase, acetylcholinesterase, and both muscarinic and nicotinic ACh receptors, making communication between both systems possible. In general, this communication down-regulates the inflammation, achieved through different mechanisms and depending on the cells involved.
Summary: With the awareness that the cholinergic anti-inflammatory pathway serves to prevent or limit inflammation in peripheral organs, vagus nerve stimulation has become a promising strategy in the treatment of several inflammatory conditions. Both pharmacological and non-pharmacological methods have been used in many studies to limit organ injury as a consequence of inflammation. Key Messages: In this review, we will highlight our current knowledge of the cholinergic anti-inflammatory pathway, with emphasis on its potential clinical use in the treatment of inflammation-triggered kidney injury.
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http://dx.doi.org/10.1159/000500920 | DOI Listing |
Am J Med Sci
September 2025
Department of Medicine, Division of Rheumatology, University of Oklahoma College of Medicine, Oklahoma City, OK; Department of Medicine, VAMC, Oklahoma City, OK. Electronic address:
Vagus nerve stimulation (VNS) has gained significant attention as a therapy for various medical conditions due to its ability to modulate chronic diseases, pain, and inflammation. VNS delivered by an implanted device is FDA approved for severe epilepsy and refractory depression. VNS delivered with implantable devices or transcutaneous methods are now being studied in several musculoskeletal diseases including osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, and fibromyalgia.
View Article and Find Full Text PDFPLoS One
September 2025
Center for Hypothalamic Research and Department of Internal Medicine, UT Southwestern Medical Center, Harry Hines blvd, Dallas, Texas, Unites States of America.
The anti-inflammatory cholinergic pathway describes the interaction between cholinergic vagal nerves and splenic immune cells, yet the exact mechanisms underlying the anti-inflammatory cholinergic pathway remain disputed. Here, we mapped the expression of key molecular components of the anti-inflammatory cholinergic pathway in the adult mouse using RNAScope in situ hybridization (ISH) and quantitative PCR (qPCR). In C57BL/6J wild-type male mice, we observed the expression of choline acetyltransferase (Chat) and alpha 7 nicotinic acetylcholine receptor (Chrna7) in various autonomic neurons throughout the body, but not in the spleen, even after bacterial lipopolysaccharide (LPS) treatment.
View Article and Find Full Text PDFImmunotargets Ther
August 2025
National and Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China.
Background: Splenic immunomodulation triggered by ultrasound shows a significant anti-inflammatory effect against various inflammatory diseases, whose mechanism is mainly attributable to the activation of cholinergic anti-inflammatory pathway (CAP). However, the potential role and underlying mechanism of splenic ultrasound stimulation in cancer management have been rarely reported and superficially defined.
Methods: Following optimization of ultrasonic parameters, this study evaluated the anti-tumor efficacy of splenic sonication across multiple tumor models (eg, orthotopic H22 hepatocellular carcinoma (HCC), orthotopic Hepa1-6 HCC, and subcutaneous 4T1 breast cancer), and applied flow cytometry to quantify dynamic alterations in immune cell populations.
Eur J Med Chem
December 2025
School of Pharmaceutical Science, School of Basic Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China; Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 42100
Recently, butyrylcholinesterase (BChE) has emerged as a potential therapeutic target for advanced Alzheimer's disease (AD). Herein, 20 novel carbamate-based N-benzoyl tryptamine derivatives were designed and synthesized by integrating a BChE-targeting fragment with the original carrier scaffold, which possesses good anti-neuroinflammatory activity. Among them, N14 was proved to be the most potent and highly selective BChE inhibitor [eqBChE IC = 18.
View Article and Find Full Text PDFNeurotoxicology
August 2025
Department of Pharmacology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran. Electronic address:
Environmental cadmium (Cd) contamination has increased in recent years, coinciding with the expansion of industrial activities and the global consumption of high-fat diets (HFD). Both are recognized as independent risk factors for neurodegenerative processes, yet their combined effects on brain function remain poorly characterized. This study is the first to investigate the interactive neurotoxicity of chronic Cd exposure and HFD, and to assess the potential protective effects of naringin, a flavonoid with known antioxidant and anti-inflammatory properties.
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