Therapeutic effect of kakkonto in a mouse model of food allergy with gastrointestinal symptoms.
BACKGROUND
The number of patients with food allergy has increased dramatically over the last several decades. However, there is no effective drug for food allergies. In the present study, we evaluated the effects of kakkonto, a traditional Japanese herbal medicine, in a mouse model of food allergy with gastrointestinal symptoms.


METHODS
BALB/c mice were systemically sensitized twice with ovalbumin (OVA) and then were repeatedly given OVA by oral intubation (OVA mice). Kakkonto was administered orally before the OVA challenges.


RESULTS
The OVA mice developed allergic diarrhea (91.8 +/- 3.8% after 6 OVA challenges), and myeloperoxidase (MPO) activity was dramatically elevated in the colons of the OVA mice. Kakkonto significantly suppressed the occurrence of allergic diarrhea and MPO activity in the OVA mice. Furthermore, the number of mucosal mast cells was greatly increased in the proximal colons of the OVA mice, and this was also suppressed by kakkonto. Interestingly, mRNA expression of helper T cell type 1 (Th1) cytokines (IFN-gamma) and Th2 cytokines (IL-4, IL-5 and IL-10) were significantly upregulated in the proximal colons of the OVA mice, an effect which was also reduced by kakkonto. Transcriptome analysis detected increased mRNA expression of suppressor of cytokine signaling-3 in the proximal colons of OVA mice, which was decreased by kakkonto administration.


CONCLUSIONS
Kakkonto has immunosuppressive effects and interferes with the infiltration of mucosal mast cells in the colons of mice with induced food allergy, leading to improvement of allergic symptoms. Kakkonto has potential as a therapeutic drug for treatment of allergic symptoms induced by the disruption of intestinal mucosal immunity.
Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, Toyama, Japan. ty@inm.u-toyama.ac.jp
Takeshi
T
Yamamoto
Kanae
K
Fujiwara
Minako
M
Yoshida
Natsuko
N
Kageyama-Yahara
Hirofumi
H
Kuramoto
Naotoshi
N
Shibahara
Makoto
M
Kadowaki
D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000235:genetics; D053818:Chymases / Q000097:blood / Q000235:genetics; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005512:Food Hypersensitivity / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007378:Interleukins / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
D018925:Chemokines; D004365:Drugs, Chinese Herbal; D007378:Interleukins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C090831:kakkon-to; D007073:Immunoglobulin E; D010047:Ovalbumin; D009195:Peroxidase; D053818:Chymases; C509230:Mcpt1 protein, mouse