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Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.
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http://dx.doi.org/10.1002/cbdv.202400290 | 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.
Neurotoxicology
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.
View Article and Find Full Text PDFMolecules
August 2025
Department of Organic Chemistry, University of Zagreb Faculty of Chemical Engineering and Technology, Trg Marka Marulića 19, HR-10 000 Zagreb, Croatia.
Background: It has been shown previously that thienobenzo-1,2,3-triazoles exhibit very good selective inhibition toward butyrylcholinesterase (BChE), while the same derivatives converted into salts also display inhibitory activity against acetylcholinesterase (AChE), enzymes relevant to Alzheimer's disease therapy. They show even better BChE inhibition potential than neutral analogs.
Methods: This study presents the synthesis and biological evaluation of a novel series of charged thienobenzo-1,2,3-triazolinium salts (-) as inhibitors of AChE and BChE.