New phytopharmaceutical agent CJ-20001 modulates stress-induced inflammatory infiltration into gastric mucosa.
OBJECTIVE
CJ-20001 is a phytopharmaceutical agent and currently being investigated in a Phase II trial for the treatment of acute and chronic gastritis patients in Korea. In this study we addressed the protective effects of CJ-20001 against water immersion restraint stress (WIRS)-induced gastric injury in rats and studied the underlying mechanisms.


METHODS
To evaluate the protective effect of CJ-20001 on stress-induced gastric lesions, rats were exposed to water immersion restraint stress. Inflammatory infiltration into gastric mucosa was examined by immunohistochemistry and in vitro invasion assay. Expression of proinflammatory cytokines was detected with reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Pretreatment with CJ-20001 dose-dependently attenuated the WIRS-induced gastric lesions as demonstrated by gross pathology and histology. WIRS increased infiltration of mast cells and macrophages into the gastric mucosa and submucosal layer, whereas the inflammatory infiltration was markedly inhibited by CJ-20001 administration. An in vitro cell invasion assay showed that treatment with CJ-20001 decreased the migration of macrophages. CJ-20001 suppressed the expression of proinflammatory cytokines, IL-18, IP-10 and GRO/KC, in lipopolysaccharides (LPS)-treated macrophages.


CONCLUSIONS
These data suggest that novel phytopharmaceutical agent CJ-20001 has the potent anti-inflammatory properties through inhibition of inflammatory infiltration in psycho-physiological stress-induced gastric injury.
Ajou University School of Medicine, Suwon, Korea. marie8346@cj.net
Marie
M
Yeo
Dong-Kyu
DK
Kim
Sung Won
SW
Cho
Song-Jin
SJ
Lee
Il-Hwan
IH
Cho
Geun-Seog
GS
Song
Byoung-Seok
BS
Moon
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005756:Gastritis / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D007101:Immersion; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020298:U937 Cells
D000893:Anti-Inflammatory Agents; C573115:CJ-20001; D016207:Cytokines; D005765:Gastrointestinal Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; D028321:Plant Preparations; D012333:RNA, Messenger