Chinese medicine · 2026
Phillyrin alleviates Kawasaki disease-induced lung inflammation by inhibiting platelet production through the NLRP3/IL-1β/NF-E2 signaling pathway.
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.
Mai Da-Hao, Huang Xiaojie, Liang Minsi, Yu Xiaoyin, Hao Wei, Yang Long-Wei, Feng Jing-Rui, Ling Xiao-Le, Wang Ke, Zhu Li, Chen Yang
Аннотация
BACKGROUND: The management of Kawasaki disease (KD)-associated complications, including thrombocytosis-driven lung inflammation, remains a clinical challenge, necessitating novel therapeutic exploration. Phillyrin, a principal bioactive compound from Forsythia suspensa (Thunb.) Vahl, has shown therapeutic promise in viral lung inflammation. However, its potential therapeutic effect and mechanism of action in KD-induced lung injury are entirely unexplored.
AIM OF THE STUDY: This study was designed to explore the therapeutic potential of phillyrin against KD-induced thrombocytosis and lung inflammation and its mechanism of action.
MATERIALS AND METHODS: C57BL/6 mice and NLRP3 knockout mice were intraperitoneal injected with Lactobacillus casei cell wall extract (LCWE) to establish models of KD-induced lung inflammation. MEG-01 cells were also stimulated with LCWE, and subsequently intervened with phillyrin and NLRP3 inhibitor MCC950. The therapeutic effects and mechanisms of phillyrin werestudied both in vivo and in vitro.
RESULTS: In the LCWE-induced mice lung inflammation model, phillyrin dose-dependently decreased circulating platelet counts and reduced CD61⁺ platelets in lung tissue. Hematological analysis demonstrated that phillyrin administration led to a significant reduction in white blood cell count. Furthermore, histopathological examination revealed attenuated inflammatory infiltration and fewer F4/80⁺ macrophages in lung sections. Bioinformatic and molecular docking analyses indicated a strong association between phillyrin's effects and the NLRP3/IL-1β axis. Mechanistic studies demonstrated that phillyrin suppressed megakaryocyte-derived platelet production by inhibiting NLRP3 inflammasome-mediated IL-1β secretion, which consequently disrupts IL-1β-driven NF-E2 expression and leads to substantial downregulation of NF-E2. Furthermore, the suppressive effects of phillyrin on megakaryocytic platelet generation and pulmonary inflammation were consistently enhanced in NLRP3-knockout mice, as well as in MEG-01 cells following either NLRP3 inactivation or IL-1 receptor antagonist treatment.
CONCLUSION: Phillyrin significantly attenuated LCWE-induced lung inflammation and suppressed megakaryocyte-derived platelet production by inhibiting the NLRP3/IL-1β axis, thereby impeding IL-1β-mediated NF-E2 expression and subsequent thrombopoiesis. These findings identify Phillyrin as a promising therapeutic candidate for Kawasaki disease by targeting the NLRP3/IL-1β/NF-E2 pathway to ameliorate pathological platelet overproduction and pulmonary complications.
AIM OF THE STUDY: This study was designed to explore the therapeutic potential of phillyrin against KD-induced thrombocytosis and lung inflammation and its mechanism of action.
MATERIALS AND METHODS: C57BL/6 mice and NLRP3 knockout mice were intraperitoneal injected with Lactobacillus casei cell wall extract (LCWE) to establish models of KD-induced lung inflammation. MEG-01 cells were also stimulated with LCWE, and subsequently intervened with phillyrin and NLRP3 inhibitor MCC950. The therapeutic effects and mechanisms of phillyrin werestudied both in vivo and in vitro.
RESULTS: In the LCWE-induced mice lung inflammation model, phillyrin dose-dependently decreased circulating platelet counts and reduced CD61⁺ platelets in lung tissue. Hematological analysis demonstrated that phillyrin administration led to a significant reduction in white blood cell count. Furthermore, histopathological examination revealed attenuated inflammatory infiltration and fewer F4/80⁺ macrophages in lung sections. Bioinformatic and molecular docking analyses indicated a strong association between phillyrin's effects and the NLRP3/IL-1β axis. Mechanistic studies demonstrated that phillyrin suppressed megakaryocyte-derived platelet production by inhibiting NLRP3 inflammasome-mediated IL-1β secretion, which consequently disrupts IL-1β-driven NF-E2 expression and leads to substantial downregulation of NF-E2. Furthermore, the suppressive effects of phillyrin on megakaryocytic platelet generation and pulmonary inflammation were consistently enhanced in NLRP3-knockout mice, as well as in MEG-01 cells following either NLRP3 inactivation or IL-1 receptor antagonist treatment.
CONCLUSION: Phillyrin significantly attenuated LCWE-induced lung inflammation and suppressed megakaryocyte-derived platelet production by inhibiting the NLRP3/IL-1β axis, thereby impeding IL-1β-mediated NF-E2 expression and subsequent thrombopoiesis. These findings identify Phillyrin as a promising therapeutic candidate for Kawasaki disease by targeting the NLRP3/IL-1β/NF-E2 pathway to ameliorate pathological platelet overproduction and pulmonary complications.