Functional genomics and metabolomics advance the ethnobotany of the #Samoan traditional medicine “matalafi”

Medicinal plants with extensive ethnobotanical histories, particularly those from Asia, have contributed to the approval of natural compounds as pharmaceutical drugs. In contrast, Samoan traditional medicine is relatively understudied. Working with traditional healers via an ethical, data sovereignty–driven collaboration led by indigenous Samoan researchers, we elucidate the chemical biology of the poorly understood but often-used Samoan traditional medicine “matalafi,” the homogenate of Psychotria insularum leaves commonly used to treat inflammation-associated illnesses. Our approach unifies genomics, metabolomics, analytical biochemistry, immunology, and traditional knowledge to delineate the mode of action of the traditional medicine rather than by the more common reductionist approach of first purifying the bioactive principles, which can be used to better understand the ethnobotany of traditional medicine.

The leaf homogenate of Psychotria insularum is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism Saccharomyces cerevisiae (baker’s yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use. Bioactivity-guided fractionation of the homogenate identified two flavonol glycosides, rutin and nicotiflorin, each binding iron in an ion-dependent molecular networking metabolomics analysis. Translating results to mammalian immune cells and traditional application, the iron chelator activity of the P. insularum homogenate or rutin decreased proinflammatory and enhanced anti-inflammatory cytokine responses in immune cells.

Together, the synergistic power of combining traditional knowledge with chemical genomics, metabolomics, and bioassay-guided fractionation provided molecular insight into a relatively understudied Samoan traditional medicine and developed methodology to advance ethnobotany.