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。钩吻素（Bicuculline，简称BIC），是抗MASLD处方“八札汤”的关键活性成分之一，已被我们研究团队初步证实，在治疗MASLD方面具有显著潜力。

目的： 本研究旨在通过调节脂质代谢和抑制NF-κB途径的肝炎来确定BIC在治疗MASLD方面的有效性，并将其作为潜在的治疗候选药物加以识别。

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

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抗MASLD的效果与其抑制NF-κB途径有关，该途径在减轻炎症和脂质沉积方面起关键作用。

结论： 本研究首次证明了BIC通过NF-κB信号通路特异性地缓解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： 钩吻素；肝脂肪变性；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。