Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a prominent and pervasive global health challenge. Bicuculline (BIC), which is a key active component of the anti-MASLD prescription "Eight Zhes Decoction", has been preliminarily shown by our research team to have significant potential in treating MASLD.

Aim: To determine BIC's efficacy in treating MASLD by regulating lipid metabolism and suppressing hepatic inflammation via nuclear factor-kappa B (NF-κB) pathway, identifying it as a therapeutic candidate.

Methods: This study explored the potential of BIC in preventing and treating MASLD using zebrafish, cellular (HepG2 and AML12), and mouse models.

Results: Our results indicate that BIC significantly reduces lipid accumulation and inflammation both in vivo and in vitro. Transcriptomic analysis suggested that the anti-MASLD effects of BIC are linked to the inhibition of the NF-κB pathway, which plays a critical role in mitigating inflammation and lipid deposition.

Conclusion: This study is the first to demonstrate that BIC specifically alleviates lipid accumulation and hepatic steatosis in MASLD models via the NF-κB signaling pathway. Overall, BIC has emerged as a promising candidate for treating MASLD.

Keywords: Bicuculline; Hepatic steatosis; Lipid accumulation; Lipid metabolism; Metabolic dysfunction-associated steatotic liver disease; Nuclear factor-kappa B.

©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.

背景: 代谢功能障碍相关脂肪性肝病（MASLD）已成为一个突出且普遍的全球健康挑战。白屈菜红碱（BIC），是抗MASLD处方“八札汤”的关键活性成分，已被我们的研究团队初步证明在治疗MASLD方面具有显著潜力。

目的: 确定BIC通过调节脂质代谢和抑制NF-κB通路介导的肝脏炎症来治疗MASLD的有效性，并将其作为潜在的治疗候选药物。

方法: 本研究使用斑马鱼、细胞（HepG2 和 AML12）以及小鼠模型探讨了BIC在预防和治疗MASLD方面的潜力。

结果: 我们的结果显示，BIC显著减少了体内和体外的脂质积累和炎症。转录组分析表明，BIC的抗MASLD效果与其抑制NF-κB通路有关，该通路在缓解炎症和脂质沉积中起关键作用。

结论: 本研究首次证明了BIC通过NF-κB信号通路特异性地减轻MASLD模型中的脂质积累和肝脂肪变性。总体而言，BIC已成为治疗MASLD的有希望的候选药物。

关键词: 白屈菜红碱；肝脏脂肪变性；脂质累积；脂质代谢；代谢功能障碍相关脂肪性肝病；核因子-κB。