دورية أكاديمية
Piper longum L. ameliorates gout through the MAPK/PI3K-AKT pathway.
| العنوان: | Piper longum L. ameliorates gout through the MAPK/PI3K-AKT pathway. |
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| المؤلفون: | Wu C; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China., Zhang Z; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China., Bai L; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China., Lei S; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China., Zou M; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China., Bao Z; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China., Ren Z; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China., Liu K; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China., Gong HH; School of Biomedical Engineering and Medical Imaging, Hubei University of Science and Technology, XianNing, Hubei Province, 437000, China. Electronic address: ghhemily@outlook.com., Ma W; Arura Tibetan Medicine Co., Ltd., State Key Laboratory of Tibetan Medicine Research and Development, Xining, China. Electronic address: 345199603@qq.com., Chen L; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China. Electronic address: clyhappy05@163.com. |
| المصدر: | Journal of ethnopharmacology [J Ethnopharmacol] 2024 Aug 10; Vol. 330, pp. 118254. Date of Electronic Publication: 2024 Apr 24. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Sequoia Original Publication: Lausanne, Elsevier Sequoia. |
| مواضيع طبية MeSH: | Piper*/chemistry , Gout*/drug therapy , Proto-Oncogene Proteins c-akt*/metabolism , Plant Extracts*/pharmacology , Plant Extracts*/chemistry , Plant Extracts*/therapeutic use , Phosphatidylinositol 3-Kinases*/metabolism, Animals ; Mice ; Male ; Molecular Docking Simulation ; Signal Transduction/drug effects ; Network Pharmacology ; Hyperuricemia/drug therapy ; Mice, Inbred C57BL ; Gout Suppressants/pharmacology ; Gout Suppressants/therapeutic use ; Gout Suppressants/isolation & purification ; Fruit/chemistry ; Disease Models, Animal ; MAP Kinase Signaling System/drug effects ; Mitogen-Activated Protein Kinases/metabolism |
| مستخلص: | Ethnopharmacological Relevance: Gout, a painful joint disease with a prevalence ranging from 0.86% to 2.2% in China over the past decade. Traditional medicine has long utilized the medicinal and edible Piper longum L. (PL) fruit spikes for treating gout and other joint conditions like rheumatoid arthritis. However, the exact mechanisms behind its effectiveness remain unclear. Aim of the Study: This study aimed to investigate the potential of alcoholic extracts from PL fruit spikes as a safe and effective treatment for gout. We used a combined network pharmacology and experimental validation approach to evaluate the mechanisms behind the anti-gout properties of PL. Materials and Methods: UPLC-Q/TOF-MS analysis determined the major components of PL. Subsequently, network pharmacology analysis predicted potential molecular targets and related signaling pathways for the anti-gout activity of PL. Molecular docking simulations further explored the interactions between PL compounds and proteins and characterized the properties of potential bioactive secondary metabolites. Mouse models of air pouch inflammation and hyperuricemia were further established, and the anti-gout mechanism of PL was confirmed by examining the expression of proteins related to the MAPK and PI3K-AKT pathways in the tissue. Results: Our analysis revealed 220 bioactive secondary metabolites within PL extracts. Network pharmacology and molecular docking results indicated that these metabolites primarily combat gout by modulating the PI3K-AKT and MAPK signaling pathways. In vivo experiments have also proven that PL at a dose of 100 mg/kg can optimally reduce acute inflammation of gout and kidney damage caused by high uric acid. The anti-gout mechanism involves the PI3K-AKT/MAPK signaling pathway and its downstream NF-κB pathway. Conclusion: This study provides compelling evidence for PL's therapeutic potential in gout management by modulating key inflammatory pathways. The findings offer a strong foundation for future clinical exploration of PL as a gout treatment option. Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Gout; MAPK; PI3K-AKT; Piper longum L |
| المشرفين على المادة: | EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 0 (Plant Extracts) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) 0 (Gout Suppressants) EC 2.7.11.24 (Mitogen-Activated Protein Kinases) |
| تواريخ الأحداث: | Date Created: 20240426 Date Completed: 20240510 Latest Revision: 20240531 |
| رمز التحديث: | 20240531 |
| DOI: | 10.1016/j.jep.2024.118254 |
| PMID: | 38670409 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-7573 |
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| DOI: | 10.1016/j.jep.2024.118254 |