Evaluation of Cypholophus macrocephalus sap as a treatment for infected cutaneous ulcers in Papua New Guinea.

Cypholophus macrocephalus sap is used to treat bacterially infected cutaneous leg ulcers in Papua New Guinea. High resolution LC-MS analysis of the sap revealed it to be rich in sulphated flavonoids. We assessed the effects of the sap on the differentiation and pro-inflammatory anti-microbial responses of M1 macrophages using IL-6 and TNF-α ELISAs and found significant increases in M1 macrophage IL-6 expression with concentrations as low as 243 ng/ml sap. Neutrophil IL-6 and TNF-α expression was also significantly increased but to a lesser degree. Matrix metalloproteinases (MMPs) 1, 2, 8 and 9 which are known to contribute to the toxic nature of wound exudates were inhibited by the sap at 24 µg/ml. The sap was tested with several bacterial species known to colonize cutaneous ulcers in Papua New Guinea but proved not to be active. Cypholophus sap stimulates pro-inflammatory, anti-microbial M1 macrophage and neutrophil responses at very low concentrations, whilst also inhibiting MMPs. The combination of an enhanced innate immune response and inhibition of MMPs in ulcer exudate, may contribute to the eradication of bacteria and healing of these infected ulcers. The sap concentrations used in these assays are readily achievable in an in vivo context.