柚皮素因其显着的特性而被广泛认可，包括抗炎、抗癌和免疫调节活性。然而，其对类风湿性关节炎（RA）的具体影响及其潜在机制仍有待探索。本研究旨在探讨柚皮素治疗胶原诱导性关节炎（CIA）的疗效及药理机制。采用DBA/1小鼠建立CIA模型，口服不同剂量的柚皮素，评估其对RA的影响。 。该研究还涉及脂多糖（LPS）诱导的 RAW264.7 细胞，以进一步评估柚皮素的作用。进行机制研究以阐明柚皮素作用所涉及的信号通路。柚皮素显着减轻 DBA/1 CIA 小鼠的足部炎症，并降低血清中促炎细胞因子的水平。它还增强了 CIA 模型的抗氧化能力。 LPS 诱导的 RAW264.7 细胞的体外研究表明，柚皮素可减弱促炎细胞因子和活性氧 (ROS) 水平。机制研究证实柚皮素激活自噬并增加自噬通量。通过沉默 Atg5 或使用氯喹抑制自噬溶酶体来阻断自噬，可有效抵消柚皮素对促炎细胞因子的影响。进一步的探索发现柚皮素激活AMPK/ULK1信号通路，抑制AMPK可逆转自噬的启动并减少柚皮素诱导的促炎细胞因子的分泌。本研究揭示了柚皮素可能用于治疗RA的新机制。它通过减少炎症、调节细胞因子水平和增强抗氧化能力，证明了柚皮素在 CIA 模型中的治疗功效。此外，通过 AMPK/ULK1 信号通路激活自噬似乎在柚皮素的抗炎作用中发挥着关键作用。这些发现提出了开发基于柚皮素的抗风湿药物的潜在策略。© 2023 作者。约翰·威利出版的《免疫、炎症和疾病》

Naringenin is widely recognized for its notable attributes, including anti-inflammatory, anti-cancer, and immunomodulatory activities. However, its specific implications for rheumatoid arthritis (RA) and the underlying mechanisms remain to be explored. This study aimed to investigate the therapeutic efficacy and pharmacological mechanism of Naringenin in the treatment of collagen-induced arthritis (CIA).A CIA model was established in DBA/1 mice, and various doses of Naringenin were administered orally to assess its impact on RA. The study also involved lipopolysaccharides (LPS)-induced RAW264.7 cells to further evaluate the effects of Naringenin. Mechanistic studies were conducted to elucidate the signaling pathways involved in Naringenin's actions.Naringenin significantly alleviated foot inflammation in DBA/1 CIA mice and attenuated the levels of pro-inflammatory cytokines in serum. It also enhanced antioxidant capacity in the CIA model. In vitro studies with LPS-induced RAW264.7 cells demonstrated that Naringenin attenuated pro-inflammatory cytokines and reactive oxygen species (ROS) levels. Mechanistic studies confirmed that Naringenin activated autophagy and increased autophagic flux. Blocking autophagy, either by silencing Atg5 or inhibiting autophagolysosome using chloroquine, effectively counteracted the impact of Naringenin on pro-inflammatory cytokines. Further exploration revealed that Naringenin activated the AMPK/ULK1 signaling pathway, and inhibition of AMPK reversed the initiation of autophagy and reduced pro-inflammatory cytokine secretion induced by Naringenin.This study unveils a novel mechanism by which Naringenin may be used to treat RA. It demonstrates the therapeutic efficacy of Naringenin in a CIA model by reducing inflammation, modulating cytokine levels, and enhancing antioxidant capacity. Moreover, the activation of autophagy through the AMPK/ULK1 signaling pathway appears to play a critical role in Naringenin's anti-inflammatory effects. These findings suggest potential strategies for the development of anti-rheumatic medications based on Naringenin.© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.