title: Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines.
abstract: Anti-inflammatory effects have been reported in Perilla frutescens leaf extract (PE), which is a plant of the genus belonging to the Lamiaceae family. We examined the effect of PE on dextran sulfate sodium (DSS)-induced colitis. Preliminarily, PE was safely administered for 7 wk without any adverse effects. In the preventive protocol, mice were fed 1.5% DSS solution dissolved in distilled water (control group) or 0.54% PE solution (PE group) ad libitum for 7 days. In the therapeutic protocol, distilled water or 0.54% PE solution was given for 10 days just after administration of 1.5% DSS for 5 days. PE intake significantly improved body weight loss. The serum cytokine profile demonstrated that TNF-α, IL-17A, and IL-10 were significantly lower in the PE group than in the control group. In the therapeutic protocol, mice in the PE group showed significantly higher body weight and lower histological colitis scores compared with mice in the control group on day 15. The serum cytokine profile demonstrated that TGF-β was significantly higher in the PE group than in the control group. In distal colon mRNA expression, TNF-α, and IL-17A were significantly downregulated. In vitro analyses of biologically active ingredients, such as luteolin, apigenin, and rosmarinic acid, in PE were performed. Luteolin suppressed production of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-17A. Apigenin also suppressed secretion of IL-17A and increased the anti-inflammatory cytokine IL-10. Rosmarinic acid increased the regulatory T cell population. We conclude that PE might be useful in treatment and prevention of DSS-induced colitis.
authors.affiliation: Department of Complementary & Alternative Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan; and h-urushima@cam.med.osaka-u.ac.jp.
authors.forename: Hayato
authors.initials: H
authors.lastname: Urushima
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Complementary & Alternative Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan; and.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Complementary & Alternative Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan; and.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Complementary & Alternative Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan; and Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ito
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood*; D008810:Mice, Inbred C57BL; D031344:Perilla frutescens / Q000737:chemistry; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005765:Gastrointestinal Agents; D018836:Inflammation Mediators; D010936:Plant Extracts; D012333:RNA, Messenger; D016264:Dextran Sulfate
keywords: Perilla frutescens; T helper 17; interleukin-17A; regulatory T cells; tumor necrosis factor-α