ABSTRACT
BACKGROUND/AIMS: 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. METHODOLOGY: 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.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Gastric Mucosa/drug effects , Gastritis/prevention & control , Gastrointestinal Agents/pharmacology , Plant Extracts/pharmacology , Plant Preparations/pharmacology , Stress, Psychological/drug therapy , Animals , Chemotaxis/drug effects , Cytokines/genetics , Cytokines/metabolism , Cytoprotection , Disease Models, Animal , Dose-Response Relationship, Drug , Gastric Mucosa/immunology , Gastric Mucosa/pathology , Gastritis/etiology , Gastritis/genetics , Gastritis/immunology , Gastritis/pathology , Humans , Immersion , Immunohistochemistry , Inflammation Mediators/metabolism , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/immunology , Male , Mast Cells/drug effects , Mast Cells/immunology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Restraint, Physical , Reverse Transcriptase Polymerase Chain Reaction , Stress, Psychological/complications , Stress, Psychological/etiology , Stress, Psychological/genetics , Stress, Psychological/immunology , Stress, Psychological/pathology , U937 CellsABSTRACT
Seungma-galgeun-tang (SGT) has been used for treatment of chronic diseases in the folk medicine recipe. Since nitric oxide (NO) is one of the major inflammatory parameters, we first studied the effects of SGT on NO production in lipopolysaccharide (LPS)-stimulated BV-2 microglia. SGT inhibited the secretion of NO in BV-2 microglia, without affecting cell viability. The protein level of inducible nitric oxide synthase (iNOS) was decreased by SGT and SGT also inhibited production of PGE(2) and expression of Cox-2. Proinflammatory cytokines, such as TNF-alpha, IL-1beta and IL-12, were inhibited by SGT in a dose-dependent manner and SGT blocked the activation of NF-kappaB, which was considered to be a potential transcription factor for the expression of iNOS, COX-2 and proinflammatory cytokines. SGT also blocked the degradation of IkappaB and activation (decrease of cytosolic p65) of NF-kappaB, p65. These results suggest that SGT could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of NF-B activity.