Native Australian fruit polyphenols inhibit COX-2 and iNOS expression in LPS-activated murine macrophages

Purified polyphenolic-rich extracts from four native Australian fruits, Illawarra Plum (Podocarpus elatus Endl., Podocarpaceae), Kakadu Plum (Terminalia ferdinandiana Exell, Combretaceae), Muntries (Kunzea pomifera F. Muell., Myrtaceae) and Native Currant (Acrotriche depressa R.Br., Epacridaceae), were screened for their ability to modulate anti-inflammatory activity in LPS-activated murine macrophages (RAW 264.7). The Kakadu Plum extract inhibited the expression of inducible nitric oxide synthase (iNOS), and importantly was the only fruit in this study that displayed differential inhibition of the expression of cyclooxygenase (COX)-2 but not COX-1. Illawarra Plum (COX-2 and iNOS) and Native Currant (iNOS only) also inhibited inflammatory enzymes, while Muntries exhibited none of these activities under the same conditions. All evaluated extracts inhibited the production of prostaglandin E₂ and nitric oxide, suggesting the involvement of alternative pathways in their regulation for the Muntries extract. Further molecular investigations, showed that Kakadu Plum inhibited the NF-??B pathway, but not the p44/42 mitogen activated protein kinase (MAPK) pathway. Collectively, these results demonstrate potential anti-inflammatory activities of native Australian fruits, in particular Kakadu Plum, in LPS-activated murine macrophages, thus confirming the potential biological activities of these fruits.