Department of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Department of Rheumatology and Immunology, The First Hospital of China Medical University, No. 155 Nanjingbei Street, Heping District, Shenyang, 110001, Liaoning, China.
Inflammation. 2021 Jun;44(3):1119-1129. doi: 10.1007/s10753-020-01407-6. Epub 2021 Jan 4.
Arthritis is characterized by irreversible joint destruction and presents a global health burden. Natural alternatives to synthetic drugs have been gaining popularity for their safety and effectiveness. Juglanin has demonstrated a range of anti-inflammatory effects in various tissues and cell types. However, the pharmacological function of Juglanin in arthritis and chondrocytes has been little studied. ATDC5 cells were treated with 1 μg/mL lipopolysaccharide (LPS) in the presence or absence of juglanin (2.5, 5 μM) for 24 h. The effects of juglanin on cellular nucleotide-binding domain leucin-rich repeat receptor 3 (NLRP3) inflammasome complex and endproduct interleukin 1β (IL-1β) and interleukin (IL-18) were assessed by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot experiments. The oxidative stress was measured by super oxide dismutase (SOD) activity and NADPH oxidase 4 (NOX4) expression. The dependent effect of juglanin on silent information regulator 2 homolog 1 (SIRT1) was evaluated by siRNA knockdown approach. Juglanin significantly reduced cellular oxidative stress by downregulating NOX4 expression production and rescuing the decreased activity of total SOD induced by LPS. Juglanin inhibited the activation of the TxNIP/NLRP3/ASC/caspase-1 axis, and decreased production of IL-1β and IL-18. Moreover, juglanin rescued the LPS-induced decrease in SIRT1 expression. SIRT1 silencing abolished the anti-NLRP3 inflammasome effect of juglanin, indicating that the effects of juglanin are dependent on its amelioration on SIRT1 expression. Juglanin possesses an anti-inflammatory and anti-ROS capacity in chondrocytes, and this study provides available evidence that juglanin may be of use in the treatment of arthritis.
关节炎的特征是关节不可逆性破坏，并构成全球健康负担。天然替代合成药物因其安全性和有效性而受到关注。 Juglanin 在各种组织和细胞类型中表现出多种抗炎作用。然而，Juglanin 在关节炎和软骨细胞中的药理学功能研究甚少。用 1μg/mL 脂多糖（LPS）处理 ATDC5 细胞，存在或不存在 Juglanin（2.5、5μM）24h。通过逆转录-聚合酶链反应（RT-PCR）、酶联免疫吸附测定（ELISA）和 Western blot 实验评估 Juglanin 对细胞核苷酸结合域富含亮氨酸重复受体 3（NLRP3）炎症小体复合物及其终产物白细胞介素 1β（IL-1β）和白细胞介素 18（IL-18）的影响。通过超氧化物歧化酶（SOD）活性和 NADPH 氧化酶 4（NOX4）表达测量氧化应激。通过 siRNA 敲低方法评估 Juglanin 对沉默信息调节因子 2 同源物 1（SIRT1）的依赖作用。Juglanin 通过下调 NOX4 表达产物和挽救 LPS 诱导的总 SOD 活性降低来显著降低细胞氧化应激。Juglanin 抑制了 TxNIP/NLRP3/ASC/caspase-1 轴的激活，并降低了 IL-1β和 IL-18 的产生。此外，Juglanin 挽救了 LPS 诱导的 SIRT1 表达降低。SIRT1 沉默消除了 Juglanin 对 NLRP3 炎症小体的抑制作用，表明 Juglanin 的作用依赖于其对 SIRT1 表达的改善。Juglanin 在软骨细胞中具有抗炎和抗 ROS 能力，本研究提供了可用的证据表明，Juglanin 可能在关节炎治疗中具有应用价值。
