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Amelioration of Juglanin against LPS-Induced Activation of NLRP3 Inflammasome in Chondrocytes Mediated by SIRT1

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Abstract

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.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China

    Tingting Wang

  2. Department of Rheumatology and Immunology, The First Hospital of China Medical University, No. 155 Nanjingbei Street, Heping District, Shenyang, 110001, Liaoning, China

    Jiakai Wang, Tao Sun & Yishuo Li

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Tingting Wang and Yishuo Li contributed to the study conception, experimental design, and data analysis; Tingting Wang, Jiakai Wang, and Tao Sun contributed to investigation and data collection; Yishuo Li contributed to the draft writing.

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Correspondence to Yishuo Li.

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Wang, T., Wang, J., Sun, T. et al. Amelioration of Juglanin against LPS-Induced Activation of NLRP3 Inflammasome in Chondrocytes Mediated by SIRT1. Inflammation 44, 1119–1129 (2021). https://doi.org/10.1007/s10753-020-01407-6

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