title: Biomarker-guided screening of Juzen-taiho-to, an oriental herbal formulation for immunostimulation.
abstract: Juzen-taiho-to is an immunostimulatory herbal formulation that is clinically used in East Asia for cancer patients undergoing chemotherapy and radiation. The formulation stimulates various leukocytes, including T, B, and NK cells and macrophages. Although Juzen-taiho-to is known to contain numerous compounds with various pharmacological activities, it is not clear which compounds are responsible for the stimulation of individual cell types. Here, we conducted what we call "biomarker-guided screening" to purify compounds responsible for the macrophages stimulatory activity. To this end, gene expression was analyzed by a DNA array for macrophages treated with Juzen-taiho-to and DMSO (vehicle control), which identified intercellular adhesion molecule 1 as a biomarker of macrophage stimulation by Juzen-taiho-to. A quantitative reverse transcription polymerase chain reaction assay of intercellular adhesion molecule 1 was then used to guide the purification of active compounds. The screening resulted in the purification of a glycolipid mixture, containing β-glucosylceramides. The glycolipid mixture potently stimulated intercellular adhesion molecule 1 expression in primary dendritic cells as well as in primary CD14+ (macrophages) cells. The identification of this glycolipid mixture opens up an opportunity for further studies to understand how plant-derived glycolipids stimulate macrophages and dendritic cells in a safe and effective manner as demonstrated by Juzen-taiho-to.
authors.affiliation: Department of Chemistry, Hunter College of CUNY, New York, NY, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Takaoka
authors.affiliation: Department of Chemistry, Hunter College of CUNY, New York, NY, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Iacovidou
authors.affiliation: Department of Chemistry, Hunter College of CUNY, New York, NY, USA.
authors.forename: Tal H
authors.initials: TH
authors.lastname: Hasson
authors.affiliation: Department of Chemistry, Hunter College of CUNY, New York, NY, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Montenegro
authors.affiliation: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Li
authors.affiliation: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA.
authors.forename: Moriya
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Chemistry, Hunter College of CUNY, New York, NY, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawamura
mesh_terms: D000276:Adjuvants, Immunologic / Q000032:analysis / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005963:Glucosylceramides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D019684:Magnoliopsida / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D005963:Glucosylceramides; C063587:juzentaihoto; D018799:Intercellular Adhesion Molecule-1