Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Discovery and characterization of hinokiflavone as a potent natural CD137 inhibitor for Kawasaki disease.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Liu Yuanfeng, Zhou JiaJing, Bai Guangyao, Zhang Yongshan, Song Qing, Zeng Chui, Huang Hong, Wang Zhouping, Cai Wenqian, Wang Yanfei
Аннотация
BACKGROUND: Kawasaki disease (KD) is a childhood systemic vasculitis of unknown etiology, with its most severe complication being the formation of coronary artery aneurysms. The pathogenesis of KD remains incompletely understood, and there is an ongoing need to develop new therapeutic agents for its treatment.
PURPOSE: This study aims to identify biomarkers and potential drug targets for KD, screen natural products with therapeutic potential based on these findings, and elucidate their mechanisms of action in depth.
METHODS: Key genes associated with KD were identified through comprehensive bioinformatics analysis. Virtual screening was subsequently performed using molecular docking, ADMET property evaluation, metabolomics analysis, molecular electrostatic potential (MEP), and frontier molecular orbital (FMO) calculations. The stability and binding free energy of the complexes were assessed via molecular dynamics simulations. Proton nuclear magnetic resonance spectroscopy was employed to verify compound purity. Surface plasmon resonance and cellular thermal shift assays were used to detect the binding affinity between compounds and proteins. Serum levels of sCD137L and sTNF-α in children with KD and healthy controls were compared using ELISA. Finally, therapeutic efficacy and underlying mechanisms were evaluated in a KD cell model.
RESULTS: CD137 was identified as a biomarker and potential drug target for KD. Hinokiflavone (HF) was identified as a candidate therapeutic agent, forming a stable complex with CD137 under physiological conditions. Serum levels of sCD137L and sTNF-α were significantly elevated in children with KD compared to healthy controls. In vitro experiments demonstrated that HF, by targeting and binding to CD137, inhibits the activation of the NLRP3 inflammasome signaling pathway induced by KD serum. siRNA-mediated knockdown of CD137 further confirmed that this intervention enhances the inhibitory effect of HF on pyroptosis, and that the pyroptosis process is dependent on CD137.
CONCLUSION: Our findings highlight the efficacy of HF in treating KD and demonstrate its broader therapeutic potential through targeted inhibition of CD137.
PURPOSE: This study aims to identify biomarkers and potential drug targets for KD, screen natural products with therapeutic potential based on these findings, and elucidate their mechanisms of action in depth.
METHODS: Key genes associated with KD were identified through comprehensive bioinformatics analysis. Virtual screening was subsequently performed using molecular docking, ADMET property evaluation, metabolomics analysis, molecular electrostatic potential (MEP), and frontier molecular orbital (FMO) calculations. The stability and binding free energy of the complexes were assessed via molecular dynamics simulations. Proton nuclear magnetic resonance spectroscopy was employed to verify compound purity. Surface plasmon resonance and cellular thermal shift assays were used to detect the binding affinity between compounds and proteins. Serum levels of sCD137L and sTNF-α in children with KD and healthy controls were compared using ELISA. Finally, therapeutic efficacy and underlying mechanisms were evaluated in a KD cell model.
RESULTS: CD137 was identified as a biomarker and potential drug target for KD. Hinokiflavone (HF) was identified as a candidate therapeutic agent, forming a stable complex with CD137 under physiological conditions. Serum levels of sCD137L and sTNF-α were significantly elevated in children with KD compared to healthy controls. In vitro experiments demonstrated that HF, by targeting and binding to CD137, inhibits the activation of the NLRP3 inflammasome signaling pathway induced by KD serum. siRNA-mediated knockdown of CD137 further confirmed that this intervention enhances the inhibitory effect of HF on pyroptosis, and that the pyroptosis process is dependent on CD137.
CONCLUSION: Our findings highlight the efficacy of HF in treating KD and demonstrate its broader therapeutic potential through targeted inhibition of CD137.