Anti-inflammatory effects of kawakawa (Piper excelsum): An integrative mRNA-miRNA approach

Kawakawa (Piper excelsum) is an endemic medicinal plant widely consumed by Māori in New Zealand. Presence of diverse biologically active phytochemicals in kawakawa may underpin its putative therapeutic anti-inflammatory properties. However, no human studies on its anti-inflammatory effects are yet undertaken. Blood samples from a randomized controlled dietary intervention exploring the impact of kawakawa compared to control on postprandial microRNAs (miRNA) abundances and their respective gene and protein targets in a cohort of healthy human volunteers (n = 26; Age; 33.6 ± 1.9 year and BMI; 22.5 ± 0.4 kg/m²) were analyzed. Postprandial levels of nine miRNAs showed differential abundances; hsa-miR-17-5p, -21-5p, -320a-5p, let-7g-5p, -16-5p, -122-5p, and -144-3p was upregulated while as hsa-miR-221-3p and -223-3p was downregulated in response to kawakawa compared to control. In silico analysis indicated enrichment of miRNAs in multiple inflammation-related pathways, including apoptosis, cytokine signaling, MAPK signaling, and MTOR pathways. Furthermore, gene expression of IL-8 (p = .03), IL-6 (p = .01), and PPAR-γ were significantly reduced following kawakawa intake compared to control. While as plasma IL-6 showed a significant increase over 120 min in the kawakawa arm. These results highlight kawakawa to exert anti-inflammatory effects by modulating the expression of miRNAs and their target genes and proteins in the inflammatory signaling pathways.