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 leaves and stems of Azadirachta indica, Psiduim guajava, Newbouldia laevis and Agerantum conyzoides collected from southeastern Nigeria using standard methods. Solid state fermentation of the isolated fungi were carried out on rice media for 21 days at 22 °C 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 method while in vitro activity against Plasmodium falciparum was determined using WHO standardized microtest system. Immunomodulatory activity of the extracts was evaluated by cyclophosphamide induced myelosuppression. Active extracts were further subjected to Delayed-Type Hypersensitivity Response (DTHR) and Haemagglutination Inhibition Assay using SRBCs as antigens. The extracts were subjected to HPLC-DAD analysis for the detection of bioactive components. The extracts showed varying degrees of antiplasmodial activity. Growth of P. berghei was significantly (p < 0.001) inhibited, curative effect ranges 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 cyclophosphamide-induced reduction in total WBC, % neutrophil, lymphocyte and monocyte level(p < 0.05). There was significant inhibition of 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, phenylacetic acid, rocaglamid and epicatechin which have been reported to have antiplasmodial and immunomodulatory activities. Extracts of endophytic fungi isolated from these Nigeria medicinal plants possess antiplasmodial and immunomodulatory activities which portends a novel approach for malaria therapy.