Protective Role of Ajmalicine Against Benzo(a)pyrene-induced Lung Cancer Through Regulation of Inflammatory and Oxidative Pathways

Background: Lung cancer is a foremost global health challenge and remains the leading cause of cancer-related mortality worldwide. Despite advancements in early diagnosis and treatment, most cases are detected at advanced stages, which severely compromises survival rates. Current chemotherapeutic agents are often limited by toxicity and resistance, highlighting the urgent need for safer and more effective preventive strategies. Objectives: The present study evaluated the chemopreventive potential of ajmalicine, an indole alkaloid, against benzo(a) pyrene (B(a)P)-induced lung carcinogenesis in rats. Materials and Methods: Lung carcinogenesis was induced by oral administration of B(a)P for 4 consecutive weeks. Ajmalicine (20 mg/kg) was administered orally 1 week before and throughout the 16-week experimental period. Posttreatment, antioxidant status, xenobiotic detoxification enzymes, inflammatory cytokines, and caspase-3/9 activities were measured using standard commercial kits. Histopathological examination of lung tissues was performed to confirm the protective role of ajmalicine. Results: Ajmalicine treatment significantly enhanced antioxidant markers while reducing xenobiotic detoxification enzyme activity in B(a)P-exposed rats. Furthermore, ajmalicine attenuated pro-inflammatory cytokines and increased caspase-3/9 activity, suggesting the induction of apoptosis. Histopathological findings corroborated its protective role by demonstrating improved lung tissue architecture. Conclusion: These findings reveal, for the first time, that ajmalicine exhibits strong chemopreventive effects against B(a) P-induced lung carcinogenesis by modulating oxidative stress, inflammation, and apoptosis. Ajmalicine may represent a promising natural candidate for preventing carcinogen-induced lung cancer.