4.8 Article

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

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2100880118

Keywords

traditional medicine; chemical biology; genomics; metabolomics; iron homeostasis

Funding

  1. Victoria University of Wellington (VUW)
  2. Health Research Council of New Zealand
  3. SROS

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The leaf homogenate of Psychotria insularum is commonly used in Samoan traditional medicine for treating various inflammatory conditions, with rutin and nicotiflorin identified as bioactive components with iron-chelating properties. Chemical genomic analyses in baker's yeast helped elucidate the iron homeostasis mechanism, and bioactivity-guided fractionation led to the discovery of the flavonol glycosides. Further research demonstrated their ability to modulate cytokine responses in immune cells, providing insight into the traditional medicine and advancing ethnobotanical methodology.
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.

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