Inflachromene is an inhibitor of HMGB1 and HMGB expression. Inflachromene can inhibit the release of HMGB1 and the NF-κB signaling pathway, exerting anti-inflammatory and neuroprotective effects. Inflachromene is mainly used to treat epilepsy [1-4].
In VSMC cells, Inflachromene (5, 10, 15, and 20μM, 24h) dramatically decreased Ang II–induced VSMC proliferation [5]. In HEK293T cells, Inflachromene (25 and 50μM, 6h) dramatically decreased the endogenous Beclin 1 protein level in a dose- and time-dependent manner whereas the levels of ATG5–ATG12 conjugate, ATG7 and ATG16L1 were not changed [6]. Inflachromene (10μM, 6d) induces senescence rapidly and homogeneously in the popular fetal lung fibroblast (IMR90) cell model, while also constraining SASP production and its paracrine effects [7].
In C57BL/6 mouse, Inflachromene (5 and 10mg/kg, ip, 14d) attenuated the neointimal formation induced by the carotid wire injury in mice [5]. In PTZ-induced seizure model, Inflachromene (3 and 10mg/kg, ip, single injection) alleviates the severity of PTZ-induced seizures in a dose-dependent manner [8]. In sepsis-associated encephalopathy (SAE) mice model, Inflachromene (10mg/kg, ip, 9d) improves cognitive impairment in SAE mice by inhibiting HMGB1-mediated microglial activation, alleviating synaptic damage and neuronal dysfunction [9]. In carbon tetrachloride (CCl4) induced liver fibrosis mouse model, Inflachromene (10mg/kg, ip, 28d) reduces HMGB2 expression and function and protects mice from liver fibrosis [10].
References:
[1]. Lee S, Nam Y, Koo JY, et al. A small molecule binding HMGB1 and HMGB2 inhibits microglia-mediated neuroinflammation. Nature chemical biology. 2014 Dec; 10(12): 1055-1060.
[2]. Teng S, Zhu Z, Wu C, et al. Inflachromene inhibits intimal hyperplasia through the HMGB1/2-regulated TLR4-NF-κB pathway. International Immunopharmacology. 2023 Jun 1; 119: 110198.
[3]. Lee HH, Im SH, Ahn S, et al. A validated UPLC-MS/MS method for pharmacokinetic study of inflachromene, a novel microglia inhibitor. Journal of Pharmaceutical and Biomedical Analysis. 2019 Mar 20; 166: 183-188.
[4]. Zhang S, Chen F, Zhai F, et al. Role of HMGB1/TLR4 and IL-1β/IL-1R1 signaling pathways in epilepsy. Frontiers in neurology. 2022 Jun 28; 13: 904225.
[5]. Teng S, Zhu Z, Wu C, et al. Inflachromene inhibits intimal hyperplasia through the HMGB1/2-regulated TLR4-NF-κB pathway. International Immunopharmacology. 2023 Jun 1; 119: 110198.
[6]. Kim YH, Kwak MS, Shin JM, et al. Inflachromene inhibits autophagy through modulation of Beclin 1 activity. Journal of Cell Science. 2018 Feb 15; 131(4): jcs211201.
[7]. Palikyras S, Sofiadis K, Stavropoulou A, et al. Rapid and synchronous chemical induction of replicative‐like senescence via a small molecule inhibitor. Aging Cell. 2024 Apr; 23(4): e14083.
[8]. Dai SJ, Shao YY, Zheng Y, et al. Inflachromene attenuates seizure severity in mouse epilepsy models via inhibiting HMGB1 translocation. Acta Pharmacologica Sinica. 2023 Sep; 44(9): 1737-1747.
[9]. Yin XY, Tang XH, Wang SX, et al. HMGB1 mediates synaptic loss and cognitive impairment in an animal model of sepsis-associated encephalopathy. Journal of Neuroinflammation. 2023 Mar 11; 20(1): 69.
[10]. Huang Y, Liangpunsakul S, Rudraiah S, et al. HMGB2 is a potential diagnostic marker and therapeutic target for liver fibrosis and cirrhosis. Hepatology Communications. 2023 Nov 1; 7(11): e0299.
Inflachromene 是HMGB1和HMGB表达的抑制剂。Inflachromene可以抑制HMGB1的释放和NF-κB信号通路，发挥抗炎和神经保护作用。Inflachromene主要用于治疗癫痫 [1-4]。
在VSMC细胞中，Inflachromene（5、10、15和20μM，24h）显著抑制血管紧张素II诱导的平滑肌细胞增殖 [5]。在HEK293T细胞中，Inflachromene（25和50μM，6h）以剂量和时间依赖性方式显著降低内源性Beclin 1蛋白水平，而ATG5-ATG12结合物、ATG7和ATG16L1的水平则没有变化 [6]。Inflachromene（10μM，6d）在常用的胎儿肺成纤维细胞（IMR90）模型中快速均匀地诱导细胞衰老，同时抑制SASP的产生及其旁分泌作用 [7]。
在C57BL/6小鼠中，Inflachromene（5和10mg/kg，ip，14d）可减弱小鼠颈动脉导线损伤引起的新生内膜形成 [5]。在PTZ诱发的癫痫模型中，Inflachromene（3和10mg/kg，ip，1次）以剂量依赖性方式减轻戊四氮诱发的癫痫严重程度 [8]。在脓毒症相关脑病（SAE）小鼠模型中，Inflachromene（10mg/kg，ip，9d）通过抑制HMGB1介导的小胶质细胞活化，减轻突触损伤和神经元功能障碍，改善SAE小鼠的认知障碍 [9]。在四氯化碳（CCl4）诱导的肝纤维化小鼠模型中，Inflachromene（10mg/kg，ip，28d）降低HMGB2的表达和功能，保护小鼠免于肝纤维化 [10]。