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Updated: May 16, 2026

Preparation of Naringenin Solution for In Vivo Application
Published on: August 10, 2021
Attenuation of NDEA-induced hepatocarcinogenesis by naringenin in rats
Perumal Subramanian1, Duraikannu Arul
1Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India. psub@rediffmail.com
Abstract:
Chemoprevention is one of the most promising and realistic approaches in the prevention of cancer. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on hepatocellular carcinoma. Naringenin is one such naturally occurring flavonoid widely found in citrus fruits. In this study, we examined the molecular mechanisms by which naringenin inhibited NDEA-induced hepatocellular carcinoma in rats by analysing the expression patterns of proliferating cell nuclear antigen, Bcl-2, NF-κB, VEGF and MMP-2/9. Enhanced cell proliferation and apoptotic evasion in NDEA-induced hepatocarcinogenesis was associated with imbalance in pro-apoptotic and anti-apoptotic proteins together with upregulation of proliferating cell nuclear antigen (PCNA) and downregulation of caspase-3. Administration of pretreatment and posttreatment of naringenin decreased the expression of PCNA and Bcl-2 and increased the expression of Bax and caspase-3, indicating antiproliferative and apoptotic effects, respectively. Administration of NDEA increased the tumour expression of NF-κB, COX-2, VEGF, MMP-2 and MMP-9 that was correlated with more aggressive lesions and tumour growth. Downregulation of NF-κB, VEGF and MMPs by naringenin seen in the present study were correlated with the inhibition of liver tumour induced by NDEA. Our results suggest that naringenin could act as a legitimate agent by inhibiting cancer processes.
Insights
Naringenin, a citrus flavonoid, shows promise in preventing liver cancer by reducing cell proliferation and promoting apoptosis. It effectively inhibits tumor growth by targeting key molecular pathways involved in hepatocellular carcinoma development.
Area of Science:
- Oncology
- Natural Product Chemistry
- Molecular Biology
Background:
- Chemoprevention using bioactive compounds from fruits and vegetables is a key strategy against cancer.
- Hepatocellular carcinoma (HCC) is a significant global health concern.
- Naringenin, a flavonoid abundant in citrus fruits, has demonstrated potential anti-cancer properties.
Purpose of the Study:
- To investigate the molecular mechanisms by which naringenin inhibits N-diethylnitrosamine (NDEA)-induced hepatocellular carcinoma in a rat model.
- To analyze the effects of naringenin on specific molecular markers associated with cancer proliferation, apoptosis, and angiogenesis.
Main Methods:
- Rats were induced with NDEA to develop hepatocellular carcinoma.
- Naringenin was administered as both a pretreatment and posttreatment.
- Expression levels of proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, caspase-3, NF-κB, COX-2, VEGF, MMP-2, and MMP-9 were analyzed.
Main Results:
- NDEA-induced HCC showed increased PCNA and Bcl-2, and decreased caspase-3, indicating enhanced proliferation and apoptosis evasion.
- Naringenin treatment reduced PCNA and Bcl-2 expression while increasing Bax and caspase-3, demonstrating antiproliferative and pro-apoptotic effects.
- Naringenin administration downregulated NF-κB, VEGF, MMP-2, and MMP-9, correlating with the inhibition of tumor growth and aggressive lesion development.
Conclusions:
- Naringenin exhibits significant antiproliferative and apoptotic effects against NDEA-induced liver cancer in rats.
- Naringenin effectively inhibits key molecular pathways including NF-κB, VEGF, and MMPs, crucial for tumor growth and angiogenesis.
- Naringenin demonstrates potential as a chemopreventive agent for hepatocellular carcinoma.

