Propolis components from stingless bees collected in Gia Lai, Vietnam, and their NRF2 activation

Stingless bee propolis is a promising source of cytoprotective metabolites. However, its chemical and biological properties, as well as its ability to modulate the nuclear factor E2-related factor 2 (NRF2) pathway, a key regulator of antioxidant response element (ARE)-driven cytoprotective gene expression, have not been adequately characterised. Compounds (1-9) were isolated from Vietnamese stingless bee propolis and identified as three xanthones and six sesquiterpenes by NMR and HR-ESI-MS analyses. Xanthone 2 and sesquiterpenes 4-9 are reported for the first time from propolis. Real-time bioluminescence monitoring using the human hepatoblastoma HepG2 reporter cell line stably expressing dual-color luciferases revealed that the ethanolic extracts dose-dependently induced NRF2 activation. Compounds 4 and 5 exhibited comparable NRF2 activation without apparent cytotoxicity. Vietnamese Homotrigona apicalis propolis is a viable source of sesquiterpenes with moderate NRF2 activation potential.