The herbal medicine compound falcarindiol from Notopterygii Rhizoma suppresses dendritic cell maturation.
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.
Mitsui
Seika
S
Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
Torii
Kan
K
Fukui
Hajime
H
Tsujimura
Kunio
K
Maeda
Akira
A
Nose
Mitsuhiko
M
Nagatsu
Akito
A
Mizukami
Hajime
H
Morita
Akimichi
A
D000287:Administration, Topical; D000818:Animals; D019661:Apiaceae / Q000737:chemistry*; D001854:Bone Marrow Cells / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects*; D053280:Diynes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007564:Japan; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D021381:Protein Transport
D016207:Cytokines; D053280:Diynes; D004365:Drugs, Chinese Herbal; D005233:Fatty Alcohols; D005456:Fluorescent Dyes; D016328:NF-kappa B; D010936:Plant Extracts; C034379:falcarindiol; D020928:Mitogen-Activated Protein Kinases; D016650:Fluorescein-5-isothiocyanate