Herbal Triad Therapy: Antiplasmodial, Immunomodulatory and Antioxidant Effects in Plasmodium berghei-Infected Mice

Background: Malaria is responsible for significant morbidity and mortality, especially in sub-Saharan Africa. Malaria can lead to complications involving vital organs such as the liver and spleen, intensifying the need for new therapeutic strategies. Historically, medicinal plants have played a crucial role in managing infectious diseases. The World Health Organisation recognises that over 80% of the global population relies on traditional medicine for healthcare needs. Aim: The study aimed to evaluate the antiplasmodial, immunomodulatory, and antioxidant effects of combined aqueous extracts of Carica papaya, Ananas comosus, and Buxus microphylla in Plasmodium berghei-infected mice. Methodology: A randomised controlled animal experimental study was conducted at the Animal House, Gregory University, Uturu, Nigeria, from March 2024 to June 2024. Sixteen (16) male Wistar mice (20–30 g) were randomly assigned to four groups: normal control, negative control (infected, untreated), standard drug (lumefantrine-treated), and plant extract combination group. Fresh plant materials were collected and authenticated by a botanist. Aqueous extracts of Carica papaya, Ananas comosus, and Buxus microphylla were prepared and administered orally. Mice were inoculated intraperitoneally with Plasmodium berghei on day 0 and treated for four consecutive days. Parasitemia, haematological indices, cytokines (IL-6, TNF-α, IFN-γ, IL-10), antioxidant enzymes (SOD, CAT, GPX, MDA, GSH), and spleen histology were assessed. Data were analysed using one-way ANOVA and Tukey’s post-hoc test at P = .05. Results: The extract combination significantly reduced parasitemia (30.28 ± 1.45%) and parasite density (778,196 ± 78,246 parasites/μL) compared to the negative control (88.48 ± 2.43%; 2,212,000 ± 127,800 parasites/μL). Haematological indices improved, including RBC (2.57 ± 0.25 × 10⁶/μL), haemoglobin (7.27 ± 0.29 g/dL), and platelets (282.33 ± 12.99 × 10³/μL). Pro-inflammatory cytokines IL-6 (17.32 ± 0.28 pg/mL) and TNF-α (86.04 ± 5.70 pg/mL) decreased, with stable IFN-γ (90.00 ± 3.62 pg/mL) and modest IL-10 increase (2.83 ± 0.00 pg/mL). Antioxidant activities improved with increased CAT (38.54 ± 0.48 U/L), reduced MDA (0.89 ± 0.02 µM), and moderate GPX (30.26 ± 3.59 U/L), while SOD and GSH rose slightly. Conclusion: Combined plant extracts demonstrated significant antiplasmodial, antioxidant, and immunomodulatory effects, supporting their potential as complementary malaria therapies. The effects reflect a multifaceted therapeutic potential, emphasising the value of integrating phytomedicine into malaria control strategies.