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Inducing Acute Liver Injury in Rats via Carbon Tetrachloride CCl4 Exposure Through an Orogastric Tube
Published on: April 28, 2020
Zanthoxylum zanthoxyloides Alkaloidal Extract Improves CCl4-Induced Hepatocellular Carcinoma-Like Phenotypes in Rats
Desmond Omane Acheampong1, Isaac Kyei Baffour1, Victor Yao Atsu Barku2
1Department of Biomedical Sciences, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.
Background:
Despite the enrollment of new small molecules such as Sorafenib for the treatment of hepatocellular carcinoma (HCC), HCC still remains a significant contributor to cancer-related mortality and morbidity globally. Zanthoxylum zanthoxyloides is long suspected of possessing anticancer bioactive compounds that may hold the prospect of adjunctive therapy against inflammation-related cancers such as HCC.
Objective:
This study assessed the effects of an alkaloidal extract of the leaves of Zanthoxylum zanthoxyloides on CCl4/olive oil (1 : 1 v/v)-induced HCC-like phenotypes in rats.
Materials And Methods:
Zanthoxylum zanthoxyloides alkaloidal extract (ZZAE) was prepared using Soxhlet and liquid-liquid extraction methods. Subsequently, ZZAE was characterized phytochemically. In the curative method, experimental HCC was established in adult (8-10 weeks old) male Sprague-Dawley rats weighing 150-300 g by twice-daily administration of CCl4/olive oil (1 : 1 v/v) (2 mL/kg ip). After confirmation of experimental HCC in rats, the rats were randomly reassigned into seven (7) groups of seven (7) rats each and treated daily for 12 weeks as follows: control (normal saline, 5 ml/kg po), model (CCl4, 5 ml/kg, ip), ZZAE (50, 100, and 200 mg/kg po), carvedilol (6.25 mg/kg po), and 20% Tween20 (1 mL/rat, po). To assess whether ZZAE has a prophylactic (preventive) effect, rats were first treated with ZZAE and later exposed to CCl4 reconstituted in olive oil.
Results:
ZZAE (100 and 200 mg/kg) and carvedilol decreased tumor incidence compared to that of control. Compared to control, ZZAE (100 and 200 mg/kg) significantly (P < 0.05) improved serum GGT. Compared to control, ZZAE improved hepatohistological distortions induced by CCl4/olive oil and also improved liver/body weight ratio. Compared to water, ZZAE arrested mitosis in the Allium cepa assay.
Conclusion:
ZZAE ameliorated CCl4/olive oil-induced HCC-like phenotype in rats and demonstrated general hepatoprotective effects by improving liver and kidney function markers. This finding rationalizes the need for further studies on ZZAE as a potential source of bioactive anti-HCC compounds.
Insights
The alkaloidal extract of Zanthoxylum zanthoxyloides (ZZAE) showed promise in reducing hepatocellular carcinoma (HCC) development in rats. ZZAE demonstrated hepatoprotective effects, suggesting its potential as a natural therapeutic agent against HCC.
Area of Science:
- Phytochemistry
- Hepatology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) remains a global health challenge despite advancements in treatment.
- Zanthoxylum zanthoxyloides is a potential source of anticancer compounds for adjunctive therapy.
Purpose of the Study:
- To evaluate the effects of Zanthoxylum zanthoxyloides alkaloidal extract (ZZAE) on HCC-like phenotypes induced by carbon tetrachloride (CCl4) in rats.
- To explore the potential of ZZAE as a natural therapeutic agent for HCC.
Main Methods:
- Preparation and phytochemical characterization of ZZAE.
- Induction of HCC-like phenotypes in Sprague-Dawley rats using CCl4/olive oil.
- Treatment of rats with ZZAE, carvedilol, or saline over 12 weeks.
- Assessment of tumor incidence, liver function markers, and hepatohistology.
Main Results:
- ZZAE (100 and 200 mg/kg) and carvedilol reduced tumor incidence in rats.
- ZZAE significantly improved serum GGT levels and hepatohistological distortions.
- ZZAE demonstrated hepatoprotective effects and arrested mitosis in the Allium cepa assay.
Conclusions:
- ZZAE ameliorated CCl4/olive oil-induced HCC-like phenotypes in rats.
- ZZAE exhibited general hepatoprotective effects, improving liver and kidney function markers.
- Further research into ZZAE as a source of anti-HCC compounds is warranted.
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