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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.
Insights
Naringenin (NAR) shows potential in treating metabolic dysfunction-associated steatohepatitis (MASH) and inhibiting early liver cancer (HCC) by reducing inflammation and extracellular matrix synthesis via the NLRP3 inflammasome pathway.
Area of Science:
- Hepatology
- Oncology
- Immunology
Background:
- Metabolic dysfunction-associated steatohepatitis (MASH) is a growing health concern linked to hepatocellular carcinoma (HCC).
- The Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in MASH progression and HCC development.
- Early intervention strategies for MASH-induced HCC are crucial.
Purpose of the Study:
- To investigate the therapeutic effects of naringenin (NAR) on early HCC in a rat MASH model.
- To elucidate the role of the NLRP3 inflammasome/pyroptosis pathway in NAR's action against MASH-associated HCC.
Main Methods:
- A rat model of MASH-induced HCC was established using a hepatopathogenic diet, carbon tetrachloride, and diethylnitrosamine.
- Naringenin (NAR) was administered orally.
- Evaluations included biochemical assays, histological analysis, in silico modeling, and molecular biological techniques.
Main Results:
- NAR significantly reduced liver damage markers, steatosis, and inflammation.
- NAR inhibited NLRP3 inflammasome activation, including caspase-1 and gasdermin D.
- NAR decreased markers of extracellular matrix synthesis and cell proliferation (e.g., TGF-β, α-SMA, collagen I, KI67).
Conclusions:
- Naringenin (NAR) demonstrates potential in inhibiting early HCC development in the context of MASH.
- NAR may exert its protective effects by modulating the NLRP3 inflammasome pathway.
- NAR could be a potential therapeutic agent for MASH treatment and prevention of associated HCC.
