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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.

Introduction: Increase in the prevalence of type-2 diabetes in Sub-Sahara Africa has created the need for robust treatment and management programs. However, an effective diabetes management program requires a high annual budget that most countries in this region cannot afford. That said, various plants and plant products in this region have either been confirmed and/or ethnopharmacologically used for the management of type-2 diabetes. Aim: To investigate the antidiabetic and insulin secretory effects of an alkaloidal extract derived from Zanthoxylum zanthoxyloides in normoglycemic and experimental diabetic rats. Materials and methods: Alkaloidal extract was prepared from leaves of Zanthoxylum zanthoxyloides (ZZAE). Nicotinamide/streptozotocin-induced type-2 diabetes was modeled in male Sprague Dawley rats weighing between 130 to 150 g. The experimental diabetic rats were grouped into six treatment groups [Model, 20% Tween20, chlorpropamide, and ZZAE (50, 100, and 150 mg/kg)], and one control group. Fasting blood glucose (FBG), and body weight were measured weekly. Rats were sacrificed 2 days after treatment under chloroform anesthesia to collect blood samples and to isolate major organs for biochemical, and histological analyses respectively. Islets of Langerhans were isolated from normoglycemic rats and co-cultured with ZZAE and chlorpropamide (10 μg/mL) to assess the insulin secretory effect of ZZAE.Results: ZZAE improved glucose kinetics curve in normoglycemic (p < 0.001) and experimental diabetic rats (p < 0.05) compared to the model. ZZAE (100 and 150 mg/kg) restored islets population, and improved kidney, and liver, histoarchitecture. ZZAE (150 mg/kg) improved post-treatment serum insulin levels compared to the model group (p < 0.001) and the Chlorpropamide group (p < 0.05). ZZAE also restored glycogen synthesis in skeletal muscles of experimental diabetic rats and stimulated insulin secretion in pancreatic islets of Langerhans isolated from normoglycemic rats. Conclusion: These results showed that ZZAE has active alkaloids that can be explored for diabetes management.

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