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Updated: May 21, 2025
Preparation of Naringenin Solution for In Vivo Application
Published on: August 10, 2021
Naringenin attenuates early hepatocarcinogenesis induced by a MASH model
Linda Vanessa Márquez-Quiroga1, Aline Barboza-López1, Jose Y Suárez-Castillo1
1Laboratorio de Hepatología Experimental, Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Av. Instituto Politécnico Nacional, No 2508 Col. San Pedro Zacatenco, CDMX, C.P. 07360, Mexico.
Introduction And Objectives:
Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role in the progression of metabolic dysfunction-associated steatohepatitis (MASH). Here, we investigated the effects of naringenin (NAR) on early hepatocellular carcinoma (HCC) experimentally induced in a rat MASH model and whether the NLRP3 inflammasome/pyroptosis pathway was involved.
Materials And Methods:
The animals were fed a hepatopathogenic diet for 16 weeks and carbon tetrachloride (400 mg/kg, i.p.) and diethylnitrosamine (40 mg/kg, i.p.) were injected once a week. NAR was administered at 100 mg/kg p.o. The effects of NAR on the MASHHCC protocol were evaluated using biochemical, histological, in silico, and molecular biological approaches.
Results:
NAR significantly mitigated liver damage, as evidenced by the reduction in liver damage markers. It also reduced steatosis and inflammation, as determined by decreased lipid accumulation and sterol regulatory element-binding protein 1C, interleukins 1-beta and 18, and nuclear factor kappa B levels, and also increased peroxisome proliferator-activated receptor gamma levels. NAR inhibits the formation of NLRP3, including the recruitment of caspase-1 and gasdermin D proteins, and reduces the levels of transforming growth factor-beta, alpha-smooth muscle actin, and hepatic collagen 1, thereby diminishing extracellular matrix synthesis. Furthermore, gamma-glutamyl transpeptidase activity, glutathione S-transferase pi 1, and the proliferation marker KI67 were considerably reduced.
Conclusions:
Our findings show that NAR has the potential to inhibit early HCC induced in the context of MASH, thereby suggesting that NAR could be used for MASH treatment in humans.
