Induction of mast cell degranulation by triterpenoidal saponins obtained from Cimicifugae rhizoma.
Cimicifugae rhizoma has been widely used as a traditional herbal medicine to treat inflammation and menopausal symptoms. In this study, we found that some of the triterpenoidal saponins purified from the ethanol extract of Cimicifugae rhizoma dramatically induced histamine release. The structure-related induction of mast cell degranulation by them and the mechanism of action were determined. β-Hexosaminidase release in HMC-1 cells was increased in a concentration-dependent manner, with maximal 6.5- and 8.5-fold increases, by 200 μg/mL 24-epi-7,8-didehydrocimigenol-3-O-xyloside (comp 1) and cimigenol 3-O-beta-d-xyloside (comp 4) compared with those treated with phorbol 12-myristate 13-acetate and A23187 (PMACI), respectively. However, β-hexosaminidase release was not changed by 7,8-dihydrocimigenol (comp 3), or 23-OAc-shengmanol-3-O-xyloside (comp 7). These triterpenoidal saponins changed neither the intracellular Ca(2+ )level nor the activation of PKC, both of which play essential roles in histamine release. However, cromolyn and ketotifen, membrane stabilizers, effectively inhibited the β-hexosaminidase release induced by comp 1 or comp 4 by 39 and 45%, respectively. Collectively, xylose on the cimigenol-related backbone among triterpene glycosides isolated from Cimicifugae rhizoma may play an important role in activating mast cells and induction of degranulation partly via membrane destabilization of mast cells.
a School of Life Sciences and Biotechnology, Korea University , Seoul , Republic of Korea ;
Ji-Yoon
JY
Choi
b Department of Food and Nutrition , Andong National University , Andong , Republic of Korea ;
Su Jin
SJ
Jeon
b Department of Food and Nutrition , Andong National University , Andong , Republic of Korea ;
Kun Ho
KH
Son
c College of Pharmacy, Korea University , Sejong , Republic of Korea.
Young In
YI
Park
a School of Life Sciences and Biotechnology, Korea University , Seoul , Republic of Korea ;
Mi-Sook
MS
Dong
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects* / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D031885:Cimicifuga / Q000737:chemistry*; D006801:Humans; D008407:Mast Cells / Q000276:immunology*; D051381:Rats; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
D012503:Saponins; D014315:Triterpenes
Cimicifugae rhizoma; HMC-1 cells; mast cell degranulation; membrane destabilization; triterpenoidal saponins