Anti‐inflammatory effects of kawakawa ( <i>Piper excelsum</i> ): An integrative mRNA–miRNA approach

Kawakawa (<i>Piper excelsum</i>) 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 (<i>n</i> = 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 <i>IL-8</i> (<i>p</i> = .03), <i>IL-6</i> (<i>p</i> = .01), and <i>PPAR-γ</i> 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.