Evaluation of Antiplasmodial and Immunomodulatory Activities of Extracts of Endophytic Fungi Isolated from four Nigerian Medicinal Plants

Endophytic fungi are the most promising source for new drugs to combat the problem of antimicrobial resistance. Twelve fungal endophytes were isolated from the leaves and stems of Azadirachta indica, Newbouldia laevis, Psidium guajava and Agerantum conyzoides using standard methods. Solid state fermentation of the isolated fungi was carried out on rice media for 21 days at 22^oC and the fungal secondary metabolites were extracted using ethyl acetate. The extracts were tested for antiplasmodial activity in vivo against Plasmodium berghei (Anka strain) using Peter and Reyley's curative test methods while in vitro activity against Plasmosium falciparum was determined using standardized WHO microtest system. Immunomodulatory activity of the extract was evaluated by cyclophosphamide unduce myelosuppresion. Active extracts were further subjected to Delayed Type Hypersensitivity Response (DTHR) and Heamaglutination Inhibition Assay using SRBCs and antigens. The extracts showed varying degree of antiplasmodial activities. Growth of P.berghei was significanlty (P < 0.001) inhibited, curative effect range from 59.09 – 100%. Schizont maturation of P.falciparum isolates was inhibited and the highest level of inhibition was observed at 1 mg/ml (P < 0.05). Seven (58.33%) of the fungal extracts showed significant counteracting effect to the cyclophosphamide-induced reduction in total WBC, % neutrophil, lymphocyte and monocyte (p < 0.05). There was a significant inhibition of the DTHR and heamagglutination induced by SRBC in rats up to 78.49 and 69.23% respectively. Correlation was positive and statistically significant between malaria and Immunomodulatory activities.observed (P = 0.036, r = 0.786). HPLC-DAD analysis revealed the presence of ferulic acid, luteolin, peperine, rocaglamid, epicatechin and phenylacetic acid which have been reported to have antiplasmodial and immunomodulatory activities. Extracts of endophytic fungi isolated from these Nigerian Medicinal plants possess antiplasmodial and immunomodulatory activities which portends a novel approach for malaria therapy.