Zanthoxylum zanthoxyloides Alkaloidal Extract Improves CCl4-Induced Hepatocellular Carcinoma-Like Phenotypes in Rats

Desmond Omane Acheampong; Isaac Kyei Baffour; Victor Yao Atsu Barku; Justice Kwaku Addo; Mainprice Akuoko Essuman; Alex Boye

doi:10.1155/2021/3804379

Zanthoxylum zanthoxyloides Alkaloidal Extract Improves CCl₄-Induced Hepatocellular Carcinoma-Like Phenotypes in Rats

Evid Based Complement Alternat Med. 2021 Jul 21:2021:3804379. doi: 10.1155/2021/3804379. eCollection 2021.

Authors

Desmond Omane Acheampong¹, Isaac Kyei Baffour¹, Victor Yao Atsu Barku², Justice Kwaku Addo², Mainprice Akuoko Essuman³, Alex Boye³

Affiliations

¹ Department of Biomedical Sciences, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.
² Department of Chemistry, School of Physical Sciences, College of Agriculture and Natural Sciences, University of Cape Coast, Cape Coast, Ghana.
³ Department of Medical Laboratory Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.

Abstract

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.