Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Mediators Inflamm. 2021 Nov 8;2021:1805147. doi: 10.1155/2021/1805147. eCollection 2021.
(Mtb) remains a significant threat to global health as it induces granuloma and systemic inflammatory responses during active tuberculosis. Mtb can induce macrophage pyroptosis, leading to the release of IL-1 and tissue damage, promoting its spread. Here, we established an in vitro Mtb-infected macrophage model to seek an effective antipyroptosis agent. Baicalin, isolated from Radix Scutellariae, was found to reduce pyroptosis in Mtb-infected macrophages. Baicalin could inhibit activation of the PERK/eIF2 pathway and thus downregulates TXNIP expression and subsequently reduces activation of the NLRP3 inflammasome, resulting in reduced pyroptosis in Mtb-infected macrophages. In conclusion, baicalin reduced pyroptosis by inhibiting the PERK/TXNIP/NLRP3 axis and might thus be a new adjuvant host-directed therapy (HDT) drug.
(结核分枝杆菌)仍然是全球健康的重大威胁,因为它在活动性肺结核期间会引起肉芽肿和全身炎症反应。结核分枝杆菌可以诱导巨噬细胞焦亡,导致 IL-1 的释放和组织损伤,从而促进其传播。在这里,我们建立了一个体外结核分枝杆菌感染的巨噬细胞模型,以寻找有效的抗焦亡剂。黄芩素从黄芩中分离出来,可减少结核分枝杆菌感染的巨噬细胞焦亡。黄芩素可以抑制 PERK/eIF2 通路的激活,从而下调 TXNIP 的表达,进而降低 NLRP3 炎性小体的激活,从而减少结核分枝杆菌感染的巨噬细胞焦亡。总之,黄芩素通过抑制 PERK/TXNIP/NLRP3 轴减少焦亡,因此可能成为一种新的宿主定向治疗(HDT)药物。