Identification and Therapeutic Potential of Polymethoxylated Flavones in <i>Citri Reticulatae Pericarpium</i> for Alzheimer’s Disease: Targeting Neuroinflammation
Neuroinflammation is a significant driving force in the pathogenesis and progression of central nervous system (CNS) disorders. Polymethoxylated flavones (PMFs), the key lipid-soluble constituents in <i>Citri Reticulatae Pericarpium</i> (CRP), exhibit excellent blood–brain barrier permea...
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2025-02-01
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| author | Xinyu Wang Zirong Yi Yiming Zhang Jing Zhang Xueyan Li Dongying Qi Qianqian Wang Xiaoyu Chai Huan Liu Guopeng Wang Yanli Pan Yang Liu Guohua Yu |
| author_facet | Xinyu Wang Zirong Yi Yiming Zhang Jing Zhang Xueyan Li Dongying Qi Qianqian Wang Xiaoyu Chai Huan Liu Guopeng Wang Yanli Pan Yang Liu Guohua Yu |
| author_sort | Xinyu Wang |
| collection | DOAJ |
| description | Neuroinflammation is a significant driving force in the pathogenesis and progression of central nervous system (CNS) disorders. Polymethoxylated flavones (PMFs), the key lipid-soluble constituents in <i>Citri Reticulatae Pericarpium</i> (CRP), exhibit excellent blood–brain barrier permeability and anti-inflammatory properties, holding therapeutic potential for CNS disorders. However, the specific bioactive components and therapeutic effects of PMFs in treating CNS disorders are not well understood. This study employed a comprehensive sequential metabolism approach to elucidate the dynamic biotransformation of PMFs in vivo and identified seven brain-targeting components. Subsequently, network pharmacology and experimental validation were utilized to explore the potential mechanisms of PMFs. The results suggested that PMFs have potential therapeutic value for Alzheimer’s disease (AD)-like mice, with the inhibition of neuroinflammation likely being a key mechanism of their anti-AD effects. Notably, sinensetin, tangeretin, nobiletin, and 3,5,6,7,8,3′,4′-heptamethoxyflavone were identified as potent neuroinflammatory inhibitors. This research elucidated the chemical and therapeutic foundations of PMFs, indicating their potential as treatments or nutritional supplements for AD prevention and treatment. Moreover, the integrated triad approach of sequential metabolism, network pharmacology, and experimental validation may serve as a promising strategy for screening bioactive compounds in herbs or functional foods, as well as for elucidating their therapeutic mechanisms. |
| format | Article |
| id | doaj-art-8191ec4e75e54fbe858405e5b0d92a72 |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-8191ec4e75e54fbe858405e5b0d92a722025-08-20T02:03:28ZengMDPI AGMolecules1420-30492025-02-0130477110.3390/molecules30040771Identification and Therapeutic Potential of Polymethoxylated Flavones in <i>Citri Reticulatae Pericarpium</i> for Alzheimer’s Disease: Targeting NeuroinflammationXinyu Wang0Zirong Yi1Yiming Zhang2Jing Zhang3Xueyan Li4Dongying Qi5Qianqian Wang6Xiaoyu Chai7Huan Liu8Guopeng Wang9Yanli Pan10Yang Liu11Guohua Yu12School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, ChinaInstitute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, ChinaZhongcai Health (Beijing) Biological Technology Development Co., Ltd., Beijing 101500, ChinaInstitute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, ChinaNeuroinflammation is a significant driving force in the pathogenesis and progression of central nervous system (CNS) disorders. Polymethoxylated flavones (PMFs), the key lipid-soluble constituents in <i>Citri Reticulatae Pericarpium</i> (CRP), exhibit excellent blood–brain barrier permeability and anti-inflammatory properties, holding therapeutic potential for CNS disorders. However, the specific bioactive components and therapeutic effects of PMFs in treating CNS disorders are not well understood. This study employed a comprehensive sequential metabolism approach to elucidate the dynamic biotransformation of PMFs in vivo and identified seven brain-targeting components. Subsequently, network pharmacology and experimental validation were utilized to explore the potential mechanisms of PMFs. The results suggested that PMFs have potential therapeutic value for Alzheimer’s disease (AD)-like mice, with the inhibition of neuroinflammation likely being a key mechanism of their anti-AD effects. Notably, sinensetin, tangeretin, nobiletin, and 3,5,6,7,8,3′,4′-heptamethoxyflavone were identified as potent neuroinflammatory inhibitors. This research elucidated the chemical and therapeutic foundations of PMFs, indicating their potential as treatments or nutritional supplements for AD prevention and treatment. Moreover, the integrated triad approach of sequential metabolism, network pharmacology, and experimental validation may serve as a promising strategy for screening bioactive compounds in herbs or functional foods, as well as for elucidating their therapeutic mechanisms.https://www.mdpi.com/1420-3049/30/4/771<i>Citri Reticulatae Pericarpium</i>polymethoxylated flavonesanti-neuroinflammationAlzheimer’s diseasesequential metabolism methodnetwork pharmacology |
| spellingShingle | Xinyu Wang Zirong Yi Yiming Zhang Jing Zhang Xueyan Li Dongying Qi Qianqian Wang Xiaoyu Chai Huan Liu Guopeng Wang Yanli Pan Yang Liu Guohua Yu Identification and Therapeutic Potential of Polymethoxylated Flavones in <i>Citri Reticulatae Pericarpium</i> for Alzheimer’s Disease: Targeting Neuroinflammation Molecules <i>Citri Reticulatae Pericarpium</i> polymethoxylated flavones anti-neuroinflammation Alzheimer’s disease sequential metabolism method network pharmacology |
| title | Identification and Therapeutic Potential of Polymethoxylated Flavones in <i>Citri Reticulatae Pericarpium</i> for Alzheimer’s Disease: Targeting Neuroinflammation |
| title_full | Identification and Therapeutic Potential of Polymethoxylated Flavones in <i>Citri Reticulatae Pericarpium</i> for Alzheimer’s Disease: Targeting Neuroinflammation |
| title_fullStr | Identification and Therapeutic Potential of Polymethoxylated Flavones in <i>Citri Reticulatae Pericarpium</i> for Alzheimer’s Disease: Targeting Neuroinflammation |
| title_full_unstemmed | Identification and Therapeutic Potential of Polymethoxylated Flavones in <i>Citri Reticulatae Pericarpium</i> for Alzheimer’s Disease: Targeting Neuroinflammation |
| title_short | Identification and Therapeutic Potential of Polymethoxylated Flavones in <i>Citri Reticulatae Pericarpium</i> for Alzheimer’s Disease: Targeting Neuroinflammation |
| title_sort | identification and therapeutic potential of polymethoxylated flavones in i citri reticulatae pericarpium i for alzheimer s disease targeting neuroinflammation |
| topic | <i>Citri Reticulatae Pericarpium</i> polymethoxylated flavones anti-neuroinflammation Alzheimer’s disease sequential metabolism method network pharmacology |
| url | https://www.mdpi.com/1420-3049/30/4/771 |
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