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Updated: May 7, 2025
Preparation of Naringenin Solution for In Vivo Application
Published on: August 10, 2021
The therapeutic role of naringenin nanoparticles on hepatocellular carcinoma
Aya G Elwan1, Tarek M Mohamed2, Doha M Beltagy3
1Biochemistry Department, Faculty of Science, Tanta University, Tanta, Egypt. ayaghaly@science.tanta.edu.eg.
Background:
Naringenin, a flavonoid compound found in citrus fruits, possesses valuable anticancer properties. However, its potential application in cancer treatment is limited by poor bioavailability and pharmacokinetics at tumor sites. To address this, Naringenin nanoparticles (NARNPs) were prepared using the emulsion diffusion technique and their anticancer effects were investigated in HepG2 cells.
Methods:
The particle size of NARNPs was determined by transmission electron microscopy and scanning electron microscopy analysis. NARNP is characterized by Fourier transform infrared spectroscopy and X-ray diffraction. Study the cytotoxic effects of various doses of naringenin, NARNPs and DOX on HepG2 and WI38 cell lines after 24 h and 48 h using the MTT assay. Flow cytometric analysis was used to study the apoptotic cells. The study also examined the expression of apoptotic proteins (p53) and autophagy-related genes ATG5, LC3 after treatment with naringenin, NARNPs, doxorubicin, and their combinations in HepG2 cells.
Results:
The particle size of NARNPs was determined by transmission electron microscopy and scanning electron microscopy analysis, showing mean diameters of 54.96 ± 18.6 nm and 31.79 ± 6.8 nm, respectively. Fourier transform infrared spectroscopy confirmed successful conjugation between naringenin and NARNPs. NARNPs were in an amorphous state that was determined by X-ray diffraction. The IC50 values were determined as 22.32 µg/ml for naringenin, 1.6 µg/ml for NARNPs and 0.46 µg/ml for doxorubicin. Flow cytometric analysis showed that NARNPs induced late apoptosis in 56.1% of HepG2 cells and had no cytotoxic effect on WI38 cells with 97% viable cells after 48 h of incubation. NARNPs induced cell cycle arrest in the Go/G1 and G2/M phases in HepG2 cells. The results showed increased expression of ATG5, LC3, and p53 in HepG2 cells treated with IC50 concentrations after 48 h of incubation. NARNPs enhanced the cytotoxic effect of doxorubicin in HepG2 cells but decreased the cytotoxic effect of doxorubicin in WI38 cells.
Conclusions:
The study demonstrated that NARNPs effectively inhibit cell proliferation and induce apoptosis in human hepatocellular carcinoma cells. Importantly, NARNPs showed no cytotoxic effects on normal cells, indicating their potential as a promising therapy for hepatocarcinogenesis. Combining NARNPs with chemotherapy drugs could present a novel approach for treating human cancers.
Insights
Naringenin nanoparticles (NARNPs) effectively target and kill liver cancer cells while sparing normal cells. This nanotechnology enhances naringenin
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Research
Background:
- Naringenin, a citrus flavonoid, exhibits anticancer properties but suffers from poor bioavailability.
- Nanoparticle formulation (NARNPs) aims to improve naringenin delivery and efficacy in cancer treatment.
Purpose of the Study:
- To develop and characterize Naringenin nanoparticles (NARNPs).
- To evaluate the anticancer effects of NARNPs on HepG2 liver cancer cells and normal WI38 cells.
Main Methods:
- Naringenin nanoparticles (NARNPs) were synthesized using emulsion diffusion.
- Particle size, morphology, and chemical properties were analyzed using TEM, SEM, FTIR, and XRD.
- Cytotoxicity was assessed using MTT assays, apoptosis via flow cytometry, and protein/gene expression (p53, ATG5, LC3).
Main Results:
- NARNPs exhibited a mean particle size of 31.79–54.96 nm and amorphous structure.
- NARNPs demonstrated significantly higher cytotoxicity against HepG2 cells (IC50: 1.6 µg/ml) compared to free naringenin (IC50: 22.32 µg/ml).
- NARNPs induced apoptosis, cell cycle arrest, and modulated key protein/gene expression in HepG2 cells, with no toxicity to WI38 cells.
Conclusions:
- Naringenin nanoparticles (NARNPs) show potent anticancer activity against hepatocellular carcinoma cells.
- NARNPs exhibit a favorable safety profile, with no observed toxicity in normal cells.
- NARNPs represent a promising nanotherapeutic strategy for liver cancer and can enhance chemotherapy efficacy.
