Alkaloidal extract from Carica papaya seeds ameliorates CCl4-induced hepatocellular carcinoma in rats

Abstract

Background Hepatocellular carcinoma (HCC) is the third cause of cancer-related mortality globally. However, available treatments are expensive and are associated with adverse effects or poor treatment outcomes in advanced disease. Meanwhile, plants like Carica papaya have demonstrated various biological activities that further studies may lead to the identification of newer and safer treatment options for HCC. Aim To evaluate the anticancer activity of an alkaloidal extract derived from Carica papaya seeds using rodent models of HCC. Experimental procedure Carica Papaya fruits were collected and authenticated. The seeds were isolated and air-dried. Alkaloidal extract was prepared from a 70% ethanol soxhlet crude extract and referred to as Carica papaya alkaloidal extract (CPAE). HCC was induced in 68 out of 84 healthy male Sprague Dawley rats by intraperitoneal injection of carbon tetrachloride (CCl 4 ) for 16 weeks. These rats were put into five groups of 10; Carica papaya alkaloidal extract [(CPAE) (50, 100, and 200 mg/kg), Lenvatinib (4 mg/kg)], 1% dimethyl sulphoxide (DMSO), and 2 untreated groups (control and model). A prophylaxis study was performed with 10 rats by co-administration of CPAE (200 mg/kg) and CCl 4 six hours apart for 16 weeks. Rats were sacrificed after a twelve-week treatment program under anesthesia for histological, hematological, and biochemical analyses. Results and conclusion CPAE (100 and 200 mg/kg) significantly restored weight loss (48.44 and 51.75% respectively), reduced tumor multiplicity, and dose-dependently reversed liver histomorphological changes induced by CCl 4 compared to the model group. The CPAE (100 and 200 mg/kg) further reduced bleeding time, improved prothrombin time and restored platelet count (p < 0.01) compared to the model. The CPAE (200 mg/kg) again significantly (p < 0.0001) reduced serum alpha-fetoprotein levels compared to the model group and prevented the establishment of HCC in rats when concerrently administered with CCl 4 in 16 weeks prophylactic study.

Bioactivity and metabolite profile of papaya (Carica papaya) seed extract

“…Based on several studies showed that papaya seed extract is effective in preventing skin inflammation caused by bacteria and parasite growth, and together with other ingredients such as chitosan may provide a better effect as an antibacterial compound (Gnanamangai et al 2022). Alkaloid extracts from papaya seeds can be used as therapeutic agents for hepatocellular carcinoma by the mechanism of increasing the histoarchitecture of liver tissue (Barffour et al 2021). The other property which is widely studied of papaya seeds is anti-cancer activity.…”