title: Anti-allergic mechanisms of Japanese herbal medicine, yokukansan on mast cells.
abstract: We previously reported that the addition of orally administered yokukansan (YKS), a traditional Japanese herbal medicine, to the standard regimen using histamine H1-receptor inhibitors was effective in controlling refractory chronic urticaria, but the mechanism remained unknown. YKS has also been reported to be effective on inhibiting the development of atopic dermatitis-like skin lesions in NC/Nga mice. As known, the release of various chemical mediators including histamine from degranulated mast cells is strongly related to the mechanism of these diseases. Thus the purpose of this study was to examine the mechanisms behind the medicinal effects of YKS on mast cells using an in vitro system and rat basophil leukemia (RBL-2H3) cells. The degree of degranulation was measured by β-hexosaminidase secretion assay and intracellular calcium influx assay. ELISA for cytokines (TNF-α and IL-4) was also conducted using cell culture media. Furthermore, we investigated the effects of YKS on the expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokine production (IL-8) in human dermal microvascular endothelial cells using gene-transcriptional- and immunohisotoligical analysis. We found that YKS inhibited secretion of β-hexosaminidase, intracellular calcium increase, production of TNF-α and ICAM-1 expression, and that several YKS ingredients may be the key effectors. In conclusion, YKS may suppress several mast cell functions such as degranulation and calcium increase that eventually inhibits the release of proinflammatory cytokines. Furthermore, YKS suppresses ICAM-1 expression on human microvascular endothelial cells. These findings may promote our understanding of the beneficial effects of YKS on mast cell-associated allergic diseases.
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamura
authors.forename: Shiori
authors.initials: S
authors.lastname: Kato
authors.forename: Takahiro A
authors.initials: TA
authors.lastname: Kato
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Mizoguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Monji
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Kanba
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D015549:Basophil Degranulation Test; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018926:Anti-Allergic Agents; D004365:Drugs, Chinese Herbal; D014409:Tumor Necrosis Factor-alpha; C524644:Yi-Gan San; D018799:Intercellular Adhesion Molecule-1; D002118:Calcium
keywords: allergy; herbal medicine; mast cells; urticaria; yokukansan