State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Orthopaedic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Phytother Res. 2019 Apr;33(4):1055-1064. doi: 10.1002/ptr.6299. Epub 2019 Jan 30.
Tectorigenin has received attention due to its antiproliferation, anti-inflammatory, and antioxidant activities. In this study, we investigated the effects of tectorigenin on lipopolysaccharide (LPS)/D-galactosamine(D-GalN)-induced fulminant hepatic failure (FHF) in mice and LPS-stimulated macrophages (RAW 264.7 cells). Pretreatment with tectorigenin significantly reduced the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histological injury, apoptosis, and the mortality of FHF mice, by suppressing the production of inflammatory cytokines such as TNF-α and IL-6. Tectorigenin also suppressed the activation of the inflammatory response in LPS-stimulated RAW 264.7 cells. Tectorigenin-induced protection is mediated through its mitigation of TLR4 expression, inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathway activation, and promotion of autophagy in FHF mice and LPS-stimulated RAW 264.7 cells. Therefore, tectorigenin has therapeutic potential for FHF in mice via the regulation of TLR4/MAPK and TLR4/NF-κB pathways and autophagy.
由于具有抗增殖、抗炎和抗氧化活性，葛根素受到了关注。本研究探讨了葛根素对脂多糖（LPS）/D-半乳糖胺（D-GalN）诱导的暴发性肝衰竭（FHF）小鼠和 LPS 刺激的巨噬细胞（RAW 264.7 细胞）的影响。葛根素预处理可通过抑制 TNF-α和 IL-6 等炎症细胞因子的产生，显著降低 FHF 小鼠的血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平、组织损伤、凋亡和死亡率，抑制炎症反应的激活。葛根素还抑制了 LPS 刺激的 RAW 264.7 细胞中炎症反应的激活。葛根素诱导的保护作用是通过减轻 TLR4 表达、抑制丝裂原活化蛋白激酶（MAPK）和核因子-κB（NF-κB）通路的激活以及促进 FHF 小鼠和 LPS 刺激的 RAW 264.7 细胞中的自噬来介导的。因此，葛根素通过调节 TLR4/MAPK 和 TLR4/NF-κB 通路和自噬，具有治疗 FHF 的潜力。
