Functional genomics of immuno-modulatory activities of medicinal plant extracts/phytocompounds in human dendritic cells/monocytes

Echinacea spp. extracts and the derived phytocompounds have been used as botanical drugs or nutraceuticals for immuno-modulatory functions [1]. Dendritic cells (DCs) play an important role in both innate and adaptive immunities. Recently, we investigated differential gene expression profiles in human immature DCs (iDCs) in response to treatment with a butanol fraction extracted from Echinacea purpurea, denoted [BF/S+L/Ep]. DNA microarray results showed significant up regulation of specific genes for cytokines (IL-8, IL-1β, and IL-18) and chemokines (CXCL 2, CCL 5, and CCL 2) within 4h after treatment. Bioinformatics analysis revealed a key-signaling network involving immune-modulatory molecules leading to the activation of a downstream adenylate cyclase 8. Proteomic analysis showed increased expression of antioxidant and cytoskeletal proteins after this treatment [1,2]. Human monocytes (THP-1) were also tested under LPS stimulation with [BF/S+L/Ep], along with three anti-inflammatory phytocompounds (emodium, shikonin and cytopiloyne). Initially (within 0.5h), shikonin [3] and emodin significantly inhibited the expression of approximately 50 genes, most notably cytokines TNF-α, IL-1 and IL-4, chemokines CCL4 and CCL8, and inflammatory modulators NFATC3 and PTGS2. Cytopiloyne and BF/S+L/Ep did not inhibit early expression of these 50 genes, but inhibited the late-stage expression (˜12 hours) for many of them, particularly IL-4, NFATC3 and PTGS2, and the cell migration and chemokine molecules CDH1 and ITGA2. The ERK 1/2 activation pathway was identified as the putative target of BF/S+L/Ep and cytopiloyne. These studies provide useful information for future development of phytocompounds/extracts as defined health supplements or herbal medicines.

Acknowledgements: Agriculture Biotechnology Research Center, Academia Sinica, Taipei, Taiwan. National Science Council , Taiwan.

References: [1] Wang, C.Y. et al. (2008) BMC Genomics. 9:479.

[2] Wang, C.Y. et al. (2006) Genomics 88:801-808.

[3] Staniforth, V. et al. (2004) J. Biol. Chem. 279:5877–5885.