PMID- 20215408 OWN - NLM STAT- MEDLINE DCOM- 20100611 LR - 20131121 IS - 1521-0103 (Electronic) IS - 0022-3565 (Linking) VI - 333 IP - 3 DP - 2010 Jun TI - The herbal medicine compound falcarindiol from Notopterygii Rhizoma suppresses dendritic cell maturation. PG - 954-60 LID - 10.1124/jpet.109.162305 [doi] AB - Dendritic cells (DCs) are important for regulating the immune response. We report an herbal medicine compound called falcarindiol that affects DC function. Ethanol extracts of 99 crude drugs that are the main components of 210 traditional Japanese medicines (Kampo medicine) approved by the Ministry of Health, Labor and Welfare in Japan were prepared and screened using the murine epidermal-derived Langerhans cell line XS106. Notopterygii Rhizoma strongly suppressed major histocompatibility complex (MHC) class II expression in XS106 cells. Activity-guided fractionation led to the isolation and identification of falcarindiol as a principal active compound in Notopterygii Rhizoma. Falcarindiol (1-5 microM) dose-dependently suppressed MHC II expression in XS106 cells. Fresh-isolated bone marrow-derived DCs were examined for the production of MHC II, CD80, CD86, interleukin (IL)-12p70, and IL-10. Treatment of bone marrow-derived DCs with 5 muM falcarindiol significantly inhibited lipopolysaccharide-induced phenotype activation and cytokine secretion and inhibited MHC II expression by CD40 ligation, but not phorbol 12-myristate 13-acetate + ionomycin or IL-12. Falcarindiol inhibited DC maturation by blocking the canonical pathway of nuclear factor-kappaB and phosphorylated p38. Topical application of 0.002 and 0.01% falcarindiol before sensitization dose-dependently suppressed delayed-type hypersensitivity to ovalbumin (p < 0.01). Falcarindiol induces immunosuppressive effects in vitro and in vivo and might be a novel therapy for autoimmune or allergic diseases. FAU - Mitsui, Seika AU - Mitsui S AD - Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan. FAU - Torii, Kan AU - Torii K FAU - Fukui, Hajime AU - Fukui H FAU - Tsujimura, Kunio AU - Tsujimura K FAU - Maeda, Akira AU - Maeda A FAU - Nose, Mitsuhiko AU - Nose M FAU - Nagatsu, Akito AU - Nagatsu A FAU - Mizukami, Hajime AU - Mizukami H FAU - Morita, Akimichi AU - Morita A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100309 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Cytokines) RN - 0 (Diynes) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Fatty Alcohols) RN - 0 (Fluorescent Dyes) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 55297-87-5 (falcarindiol) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - I223NX31W9 (Fluorescein-5-isothiocyanate) SB - IM MH - Administration, Topical MH - Animals MH - Apiaceae/*chemistry MH - Bone Marrow Cells/drug effects MH - Cell Line MH - Cytokines/biosynthesis MH - Dendritic Cells/*drug effects MH - Diynes/administration & dosage/isolation & purification/*pharmacology MH - Drugs, Chinese Herbal MH - Fatty Alcohols/administration & dosage/isolation & purification/*pharmacology MH - Female MH - Flow Cytometry MH - Fluorescein-5-isothiocyanate MH - Fluorescent Dyes MH - Hypersensitivity, Delayed/prevention & control MH - Japan MH - Magnetic Resonance Spectroscopy MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinases/metabolism MH - NF-kappa B/metabolism MH - Plant Extracts/chemistry/pharmacology MH - Protein Transport EDAT- 2010/03/11 06:00 MHDA- 2010/06/12 06:00 CRDT- 2010/03/11 06:00 PHST- 2010/03/11 06:00 [entrez] PHST- 2010/03/11 06:00 [pubmed] PHST- 2010/06/12 06:00 [medline] AID - jpet.109.162305 [pii] AID - 10.1124/jpet.109.162305 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2010 Jun;333(3):954-60. doi: 10.1124/jpet.109.162305. Epub 2010 Mar 9.