Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland.
Doctoral School, Poznan University of Medical Sciences, Bukowska 70, 60-812 Poznan, Poland.
Int J Mol Sci. 2024 Oct 18;25(20):11213. doi: 10.3390/ijms252011213.
Liver inflammation is frequently linked to oxidative stress and dysregulation of bile acid and fatty acid metabolism. This review focuses on the farnesoid X receptor (FXR), a critical regulator of bile acid homeostasis, and its interaction with the nuclear factor erythroid 2-related factor 2 (Nrf2), a key modulator of cellular defense against oxidative stress. The review explores the interplay between FXR and Nrf2 in liver inflammatory diseases, highlighting the potential therapeutic effects of natural FXR agonists. Specifically, compounds such as auraptene, cafestol, curcumin, fargesone A, hesperidin, lycopene, oleanolic acid, resveratrol, rutin, ursolic acid, and withaferin A are reviewed for their ability to modulate both the FXR and Nrf2 pathways. This article discusses their potential to alleviate liver inflammation, oxidative stress, and damage in diseases such as metabolic-associated fatty liver disease (MAFLD), cholestatic liver injury, and viral hepatitis. In addition, we address the molecular mechanisms driving liver inflammation, including oxidative stress, immune responses, and bile acid accumulation, while also summarizing relevant experimental models. This review emphasizes the promising therapeutic potential of targeting both the Nrf2 and FXR pathways using natural compounds, paving the way for future treatments for liver diseases. Finally, the limitations of the clinical application were indicated, and further research directions were proposed.
肝脏炎症通常与氧化应激以及胆汁酸和脂肪酸代谢失调有关。本综述重点关注法尼醇 X 受体 (FXR)，它是胆汁酸动态平衡的关键调节因子，以及其与核因子红细胞 2 相关因子 2 (Nrf2) 的相互作用，Nrf2 是细胞对抗氧化应激的主要调节因子。本综述探讨了 FXR 和 Nrf2 在肝脏炎症性疾病中的相互作用，强调了天然 FXR 激动剂的潜在治疗效果。具体而言，研究了奥瑞因、咖啡醇、姜黄素、法呢酯 A、橙皮苷、番茄红素、齐墩果酸、白藜芦醇、芦丁、熊果酸和吴茱萸次碱等化合物在调节 FXR 和 Nrf2 通路方面的能力。本文讨论了它们在代谢相关脂肪性肝病 (MAFLD)、胆汁淤积性肝损伤和病毒性肝炎等疾病中缓解肝脏炎症、氧化应激和损伤的潜力。此外，我们还探讨了驱动肝脏炎症的分子机制，包括氧化应激、免疫反应和胆汁酸积累，并总结了相关的实验模型。本综述强调了使用天然化合物靶向 Nrf2 和 FXR 通路的有前途的治疗潜力，为肝脏疾病的未来治疗铺平了道路。最后，指出了临床应用的局限性，并提出了进一步的研究方向。
