Objective: This research aimed to delineate the pharmacological mechanisms of 7-Hydroxycoumarin (7-HC) on ulcerative colitis (UC) employing network pharmacology and experimental validation.
Methods: To investigate the therapeutic effects of 7-HC on UC, a UC mouse model was established through the unrestricted intake of 3.0% dextran sulfate sodium (DSS) in their drinking water. Subsequently, we predicted the core targets and signaling pathways of 7-HC for the treatment of UC using the network pharmacology approach. Finally, the insights gained from network pharmacology were further validated by molecular docking, molecular dynamics simulation as well as in vivo experiments.
Results: Administering 7-HC orally to mice with UC led to a marked improvement in colitis indicators. Furthermore, 7-HC significantly lowered the levels of inflammatory cytokines (TNF-α, IL-1β) in the colon and modulated oxidative stress markers (MPO, SOD). Subsequent studies identified 2 core targets (AKT1 and EGFR) in the colon of UC mice that were inhibited by 7-HC. Network pharmacology and experimental validation showed that 7-HC can reduce the expression of MAPK pathway markers P38, JNK, ERK, and their phosphorylation; 7-HC can also ameliorate UC by regulating the gut microbiome.
Conclusion: 7-HC demonstrates considerable efficacy in alleviating UC in mice, primarily through substantial diminution of tissue inflammation and oxidative stress. This is the first time that 7-HC has been found to treat UC by inhibiting the MAPK pathway and modulating the gut microbiota, providing a fresh perspective on the pharmacological mechanisms through which 7-HC operates in the management of UC.
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http://dx.doi.org/10.1186/s12876-024-03499-y | DOI Listing |
Mol Psychiatry
December 2024
Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA.
The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples.
View Article and Find Full Text PDFJ Ethnopharmacol
December 2024
Department of Rheumatology and Immunology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510280, China; School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, 510515, China; Guangdong Province Key Laboratory of Immune Regulation and Immunotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address:
Ethnopharmacological Relevance: Tinospora crispa (L.) Hook.f.
View Article and Find Full Text PDFJ Ethnopharmacol
December 2024
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China; Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences; NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance. Electronic address:
Ethnopharmacological Relevance: Myristica fragrans (Nutmeg) is a commonly used Chinese herbal medicine and edible spice. According to Pharmacopoeia of People's Republic of China, it has the effects of warming the middle and promoting qi, astringent intestines, and antidiarrheal. In the record of Compendium of Materia Medica, it is the myristica fragrans water extract (MFWE) that is utilized for therapeutic purposes of gastrointestinal disorders frequently.
View Article and Find Full Text PDFJACC Clin Electrophysiol
November 2024
Department of Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, Minnesota, USA; Department of Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), Mayo Clinic, Rochester, Minnesota, USA; Department of Cardiovascular Medicine (Division of Heart Rhythm Services, Windland Smith Rice Genetic Heart Rhythm Clinic), Mayo Clinic, Rochester, Minnesota, USA. Electronic address:
Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare, potentially life-threatening genetic heart disease. Nonselective beta-blockers (BBs) are highly effective in reducing CPVT-triggered arrhythmic events. However, some patients suffer from unacceptable BB side effects and might require strategies without a BB.
View Article and Find Full Text PDFIntegr Cancer Ther
December 2024
Department of Surgery, College of Medicine, Taif University, Taif, Saudi Arabia.
Background: Breast cancer is a critical threat to human health, and effective targeted agents showing lower systemic toxicity are still lacking. Therefore, exploring new potent therapeutic candidates with a broader safety margin is warranted. Alternative medicine, which has historically been used in traditional Chinese medicine, has played an increasingly prominent role in this area of research.
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