Azadirachta indica extract alleviates the progression of cholangiocarcinoma in liver fluke-infected hamsters

• Neem leaf extract (NLE) were increased survival rates, lowered liver/body weight ratio, reduced bile duct proliferation, inflammation, and tumor formation. • Neem leaf extract (NLE) were decreased Carbohydrate antigen 19–9 (CA19–9) expression. • Neem extracts downregulated oxidant-generating genes and proinflammatory cytokines, while upregulating the antioxidant gene. • Neem extract exhibits chemopreventive potential against CCA by suppressing NF-κB. Cholangiocarcinoma (CCA) caused by chronic infection with the liver fluke Opisthorchis viverrini ( O. viverrini ), a common and prevalent cancer in Southeast Asia, including Northeast Thailand has limited preventive options. Neem ( Azadirachta indica ) leaf extract possesses anti-inflammatory, hepatoprotective, and anticancer activities through apoptosis induction, inhibition of tumor cell proliferation, and angiogenesis suppression in various cancer types, but its hepatoprotective effects during CCA progression are unknown. To investigate the chemopreventive effect of neem leaf extract on CCA progression and liver injury. Hamsters were administered with a combination of O. viverrini infection and NDMA and treated with neem leaf extract (100 mg/kgbw) for 2, 4 and 6 months. Neem leaf extract group were increased survival rates, lowered liver/body weight ratio, reduced bile duct proliferation, inflammation, and tumor formation. Immunohistochemistry showed decreased Carbohydrate antigen 19–9 (CA19–9) expression in neem leaf treated. Neem extracts downregulated oxidant-generating genes and proinflammatory cytokines, while upregulating the antioxidant gene [nuclear erythroid 2-related factor 2 (Nrf2)]. Neem extract exhibits chemopreventive potential against CCA by suppressing NF-κB.