The present study was designed to evaluate the immunopharmacological effects of Artemisia annua, the isolated compound artemisinin, and its semi-synthetic derivative artemether, administered orally to Nile tilapia (Oreochromis niloticus) during experimental infection with Aeromonas hydrophila. The dosage used was equivalent to 9.6 mg/kg of feed, and the experimental design included both vaccinated and non-vaccinated fish in order to assess the combined effects of immunization and immunomodulatory therapy. Following cultivation and harvesting of A. annua, artemisinin and artemether were extracted by HPLC-RI. Eight experimental groups were established: The experimental design consisted of eight groups: vaccinated and non-vaccinated fish, each either untreated or treated with A. annua, artemisinin, or artemether. Diets supplemented with the plant material or compounds were administered for 15 days prior to vaccination. The vaccination protocol consisted of two intraperitoneal doses of a bacterin prepared from A. hydrophila (8.6 × 10⁸ cells/mL, 0.05 mL per fish) given at a 15-day interval. After vaccination, experimental diets continued for15 days, coinciding with the induction of acute inflammation, which was evaluated at 24, 48, and 72 hours post-inoculation. A comprehensive set of immune and physiological parameters was analyzed to determine the modulatory effects of treatments. These included: accumulation of leukocytes in the inflammatory exudate, leukogram profiles, respiratory burst activity of leukocytes, serum levels of acute-phase proteins, biochemical markers of hepatic and renal function, and antibody titers. The correlations among these variables provided the influence of treatments on both innate and adaptive immune responses. The results demonstrated that A. annua, artemisinin, and artemether all exerted positive immunomodulatory effects in tilapia challenged with A. hydrophila. Among them, artemether produced the most pronounced responses, characterized by enhanced antibody production at earlier time points, stronger modulation of inflammatory processes, and improved regulation of reactive oxygen species (ROS) generation. Importantly, none of the treatments compromised liver or kidney function, underscoring their safety for application in aquaculture systems. Therefore, the study highlights the potential of A. annua-derived compounds, particularly artemether, as safe and effective immunopharmacological agents for enhancing disease resistance in Nile tilapia aquaculture. Their capacity to modulate inflammatory responses, stimulate both innate and adaptive immunity, and maintain physiological homeostasis suggests that they may serve as promising alternatives or complementary tools to conventional prophylactic and therapeutic measures, thereby contributing to sustainable and health-oriented fish farming practices.
Keywords: Cichlids, Pharmacognosy, Vaccine, Bacteriosis, Innate Immunity, Antibodies
Acknowledgments: This study was financed by the São Paulo Research Foundation – FAPESP. process number: 2023/18386-4