Wang XM, Dai Z, Lu DJ, Bao CQ, Yang NB, Zhou YP. Bicuculline ameliorates metabolic dysfunction-associated steatotic liver disease by inhibiting the nuclear factor-kappa B pathway and reducing lipid accumulation. World J Gastroenterol 2025; 31(17): 105438 [PMID: 40521270 DOI: 10.3748/wjg.v31.i17.105438]
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08628847
Submitted on:
May 03, 2025, 14:36
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Reader Comments:
This article investigates the therapeutic potential of BIC in the context of MASLD, with a particular focus on its effects on lipid metabolism and inflammation. BIC, an alkaloid traditionally recognized as a GABA receptor antagonist, is presented as a novel therapeutic candidate for MASLD. This exploration is particularly intriguing, as the GABAergic pathways are well-documented for their roles within the nervous system; however, the investigation into BIC’s impact on hepatic lipid metabolism and inflammatory processes remains relatively novel and promising. The utilization of zebrafish, HepG2, and AML12 cellular models, alongside mouse models induced by a MCD diet, significantly enhances the validity of the findings. By employing multiple experimental models, the researchers provide robust evidence supporting the efficacy of BIC in alleviating MASLD, which is essential for the translation of these findings into clinical practice. Furthermore, the absence of significant toxicity observed in zebrafish embryos and cellular models, even at relatively high concentrations of BIC, suggests a favorable safety profile for this compound. This aspect is critical, as it bolsters the notion that BIC could potentially be developed into a therapeutic agent devoid of the toxic effects commonly associated with alternative treatments. However, while the study offers compelling evidence from preclinical models, it is imperative to investigate the long-term effects of BIC. Given that MASLD can progress to more severe forms, such as steatohepatitis and fibrosis, long-term studies are necessary to ascertain whether BIC can effectively prevent such progression. Moreover, although the results of the study confirm the absence of significant toxicity associated with the drug, the relationship between its pharmacological mechanisms and GABA warrants further discussion, or at the very least, should be acknowledged in the limitations section.
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