title: Liquiritigenin, a licorice flavonoid, helps mice resist disseminated candidiasis due to Candida albicans by Th1 immune response, whereas liquiritin, its glycoside form, does not.
abstract: Licorice (the root of Glycyrrhizae plant) has been used as an oriental herbal medicine for thousands of years. The licorice flavonoid components are reported to possess immunomodulatory activities. In this present study, we investigated the immunomodulatory effects of liquiritigenin (LG) and liquiritin (LQ), licorice flavonoid components, against disseminated candidiasis due to Candida albicans, a dimorphic fungus, that causes severe disease via hematogenous dissemination and local diseases such as vaginitis and thrush. Results showed that direct interaction of LG or LQ with C. albicans yeast cells resulted in no growth-inhibition, in vitro. When tested in a murine model of disseminated candidiasis, mice given LQ intraperitoneally before intravenous challenge with live C. albicans yeast cells had similar mean survival times (MST) as untreated mice groups. On the contrary, mice given LG in the same manner as LQ above had longer MST than the untreated mice groups (P < 0.05). In one experiment, 3 out of 5 LG-treated mice survived during the entire period of the 55-day observation. Furthermore, the 3 survivors were cured -- shown by a lack of CFU (colony forming unit) in the kidneys. This protection was nulled when mice were pretreated with anti-CD4+ antibody before LG-treatment and challenge with the yeast. However, the protection was transferable by the CD4+ T cells isolated from LG-treated mice not infected with the yeast. In addition, mice given CD4+ T cells that were pre-treated with LG, in vitro were also protected against disseminated candidiasis. ELISA analysis revealed that in LG-treated mice IFNgamma and IL-2 were dominantly produced compared to IL-4 and IL-10. When LG-given mice were treated with anti-mouse IFNgamma, the protection was again nulled. Combined together, these results indicate that LG protects mice against disseminated candidiasis by the CD4+ Th1 immune response.
authors.affiliation: Department of ImmunoMicrobiology, College of Pharmacy, Dongduk Women's University, Sungbuk-Gu, Seoul, Republic of Korea.
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jue-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Park
authors.forename: Song-Yi
authors.initials: SY
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Eui-Chan
authors.initials: EC
authors.lastname: Jang
authors.forename: Yongmoon
authors.initials: Y
authors.lastname: Han
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D019138:Antibodies, Blocking; D002176:Candida albicans; D002177:Candidiasis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D044950:Flavanones / Q000008:administration & dosage*; D005960:Glucosides / Q000008:administration & dosage*; D006035:Glycyrrhiza; D007111:Immunity, Cellular / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008517:Phytotherapy; D018517:Plant Roots; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000890:Anti-Infective Agents; D019138:Antibodies, Blocking; D016207:Cytokines; D044950:Flavanones; D005960:Glucosides; C512196:liquiritin; C083152:liquiritigenin