title: Paeonia japonica, Houttuynia cordata, and Aster scaber water extracts induce nitric oxide and cytokine production by lipopolysaccharide-activated macrophages.
abstract: Natural products are increasingly recognized as potential targets for drug discovery and development. We previously reported that Paeonia japonica, Houttuynia cordata, and Aster scaber enhanced macrophage activation both in vitro and in vivo. In the present study we investigated the immunomodulating effects of these plants on lipopolysacharide (LPS)-stimulated macrophages. An aqueous extract of each plant was administered to female BALB/c mice every other day for 4 weeks. Peritoneal macrophages were then collected and incubated to examine the immunoreactivity of macrophages against LPS at different time points. The expression levels of inducible nitric oxide (NO) synthetase (iNOS), cyclooxygenase (COX)-2, and inhibitory factor kappaB alpha (IkappaBalpha) proteins and the production of NO metabolite (nitrite), prostaglandin (PG) E(2), and the pro-inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha were determined in the activated macrophages treated with extracts from each plant individually or combined. High levels of pro-inflammatory cytokines were produced by A. scaber-, P. japonica-, and H. cordata-treated macrophages following 24 hours of LPS stimulation. P. japonica, H. cordata, and A. scaber treatment also induced the production of nitrate by LPS-treated macrophages. Induction of iNOS mRNA and protein was also different in each group. PGE(2) secretion was up-regulated by all extract-treated macrophages at early time points; however, no significant differences were observed between the groups by 8 hours post-LPS stimulation. Treatment with A. scaber extract resulted in the highest levels of IkappaBalpha degradation. Our findings illustrate that the natural plant products P. japonica, H. cordata, and A. scaber may enhance immune function by modulating ex vivo pro-inflammatory cytokine and NO production as well as the expression of iNOS and COX-2.
authors.affiliation: College of Human Ecology, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Chang-Shin
authors.initials: CS
authors.lastname: Park
authors.forename: Yunsook
authors.initials: Y
authors.lastname: Lim
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D031173:Aster Plant / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D052859:Houttuynia / Q000737:chemistry; D020672:I-kappa B Proteins / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D029596:Paeonia / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D004365:Drugs, Chinese Herbal; C442781:Houttuynia cordata extract; D020672:I-kappa B Proteins; D007155:Immunologic Factors; D008070:Lipopolysaccharides; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D010936:Plant Extracts; D011458:Prostaglandins E; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2