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

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.

Citrus limon (L.) Osbeck Fruit Peel Extract Attenuates Carbon Tetrachloride-Induced Hepatocarcinogenesis in Sprague-Dawley Rats

“…Trichloromethyl peroxyl radical induces lipid peroxidation and oxidative stress as a result of the generation of endogenous lipid radicals from unsaturated fatty acids within membranes of hepatic cells [ 24 ]. When the liver damage due to the generation of endogenous lipid radicals proceeds without treatment, it sets in motion a number of pathological transformations leading to the establishment of HCC-like phenotypes in rats [ 26 ]. Thus, to assess the prophylactic hepatoprotective and anti-HCC effects of LPE, three functional hallmarks of the liver, namely, metabolic, biosynthetic, and detoxification were monitored using endpoints such as survival rate, body weight changes, gross liver anatomy, liver histology, biochemical parameters ( α -fetoprotein, C-reactive protein, albumin, total protein, prothrombin time, AST, ALT, ALP, GGT, and bilirubin), and hematological assessments.…”

A Proposed Association between Improving Energy Metabolism of HepG2 Cells by Plant Extracts and Increasing Their Sensitivity to Doxorubicin

“…Natural products have been widely reported for their cytotoxic effects by acting as antioxidants, anti-proliferative, and/or apoptotic agents [ 46 ]. A recent study explored the novel role of phytochemicals in overcoming resistance to chemotherapy and sensitizing cancer cells to different anticancer drugs [ 47 ].…”

Wound Healing Properties and Antimicrobial Effects of Parkia clappertoniana Keay Fruit Husk Extract in a Rat Excisional Wound Model

“…Mechanistically, it was observed that PCFHE exerts bacteriostatic effects against the test microorganisms over a period of 6-24 hours ( Figure 7 ). The bioactivity of medicinal plants has always been attributed to their phytochemical composition and functional group enrichment [ 39 ].…”