The (2'S,7'S)-O-(2-methylbutanoyl)-columbianetin as a novel allergic rhinitis-control agent.
OBJECTIVE
The (2'S,7'S)-O-(2-methylbutanoyl)-columbianetin (OMC) is a novel secondary metabolite extracted from Corydalis heterocarpa, which has long been used as a folk medicine for various inflammatory diseases in Korea. We examined the effect of OMC on allergic rhinitis (AR).


METHODS
We assessed the therapeutic effects and regulatory mechanisms of OMC on the phorbol 12-myristate 13-acetate plus A23187-stimulated mast cell line, HMC-1 cells and ovalbumin (OVA)-induced AR models.


RESULTS
OMC significantly decreased the releases of histamine and tryptase from stimulated HMC-1 cells. The degranulation process, characterized by morphological extension of the filopodia on the surface and membrane ruffling, was strongly induced in the stimulated-HMC-1 cell, however OMC suppressed the morphological changes in stimulated-HMC-1 cells. OMC reduced the production and mRNA expression of inflammatory cytokines. These inhibitory actions by OMC were dependent on the regulation of mitogen-activated protein kinases, nuclear factor-κB, and caspapase-1 signaling pathways. In the AR animal model, the increased rub scores and AR biomarkers (histamine and IgE) in ovalbumin (OVA)-sensitized mice were significantly reduced by the administration of OMC. Furthermore, eosinophils and mast cell infiltrations in nasal mucosa tissue were also blocked through the regulation of macrophage-inflammatory protein and intercellular adhesion molecule-1 levels.


CONCLUSIONS
OMC showed the possibility to regulate AR in activated mast cells and OVA-induced AR models. Hence, we suggest that OMC is a powerful and feasible new agent to suppress AR.
Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
Sun-Young
SY
Nam
High-Enthalpy Plasma Research Center, Chonbuk National University, Republic of Korea.
Min-Ho
MH
Kim
Division of Marine Environment & Bioscience, Korea Maritime University, Busan, Republic of Korea.
Youngwan
Y
Seo
Biochip Research Center and Inflammatory Disease Research Center, Hoseo University, 165, Sechul-ri, Baebang-myun, Asan, Chungnam 336-795, Republic of Korea.
Youngjin
Y
Choi
Regional Innovation Center and Inflammatory Disease Research Center, Hoseo University, 165, Sechul-ri, Baebang-myun, Asan, Chungnam 336-795, Republic of Korea.
Jae-Bum
JB
Jang
Biochip Research Center and Inflammatory Disease Research Center, Hoseo University, 165, Sechul-ri, Baebang-myun, Asan, Chungnam 336-795, Republic of Korea.
In-Cheol
IC
Kang
Oriental Bio-herb Research Institute, Kangwon National University, Chuncheon 200-701, Republic of Korea.
Myong-Jo
MJ
Kim
School of Biomedical Sciences, Charles Sturt University, Bathurst, NSW 2795, Australia.
Sok Cheon
SC
Pak
Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea. Electronic address: hmkim@khu.ac.kr.
Hyung-Min
HM
Kim
Biochip Research Center and Inflammatory Disease Research Center, Hoseo University, 165, Sechul-ri, Baebang-myun, Asan, Chungnam 336-795, Republic of Korea. Electronic address: hjjeong@hoseo.edu.
Hyun-Ja
HJ
Jeong
D000818:Animals; D061945:Caspase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*
C548753:(2'S,7'S)-O-2-methylbutanoyl-columbianetin; D061945:Caspase Inhibitors; D003374:Coumarins; D016207:Cytokines
(2′S,7′S)-O-(2-methylbutanoyl)-columbianetin; Allergic rhinitis; Caspase-1; Degranulation; Mast cells