In this study, we investigated the inhibitory activities on gastritis and gastric ulcer using liriodendrin which is a constituent isolated from Kalopanax pictus. To elucidate its abilities to prevent gastric injury, we measured the quantity of prostaglandin E2 (PGE2) as the protective factor, and we assessed inhibition of activities related to excessive gastric acid be notorious for aggressive factor and inhibition of Helicobacter pylori (H. pylori) colonization known as a cause of chronic gastritis, gastric ulcer, and gastric cancer. Liriodendrin exhibited higher PGE2 level than rebamipide used as a positive control group at the dose of 500 microM. It was also exhibited acid-neutralizing capacity (10.3%) and H+/K+-ATPase inhibition of 42.6% (500 microM). In pylorus-ligated rats, liriodendrin showed lower volume of gastric juice (4.38 +/- 2.14 ml), slightly higher pH (1.53 +/- 0.41), and smaller total acid output (0.47 +/- 0.3 mEq/4 hrs) than the control group. Furthermore liriodendrin inhibited colonization of H. pylori effectively. In vivo test, liriodendrin significantly inhibited both of HCl/EtOH-induced gastritis (46.9 %) and indomethacin-induced gastric ulcer (46.1%). From these results, we suggest that liriodendrin could be utilized for the treatment and/or protection of gastritis and gastric ulcer.
Animals ; Colon ; Dinoprostone ; Gastric Acid ; Gastric Juice ; Gastritis ; Helicobacter pylori ; Hydrogen-Ion Concentration ; Kalopanax* ; Rats ; Stomach Neoplasms ; Stomach Ulcer

BACKGROUND: The stem bark of Kalopanax pictus (KP) has been used in traditional medicine to treat rheumatoidal arthritis, neurotic pain and diabetes mellitus in China and Korea. In this study, the mechanism responsible for anti-inflammatory effects of KP was investigated. METHODS: We examined the effects of KP on NO production, nitric oxide synthase (iNOS) and HO-1 expression, NF-kappaB, Nrf2 and MAPK activation in mouse peritoneal macrophages. RESULTS: The aqueous extract of KP inhibited LPS-induced NO secretion as well as inducible iNOS expression, without affecting cell viability. KP suppressed LPS-induced NF-kappaB activation, phosphorylation and degradation of IkappaB-alpha, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Furthermore, KP induced HO-1 expression and Nrf2 nuclear translocation. CONCLUSION: These results suggest that KP has the inhibitory effects on LPS-induced NO production in macrophages through NF-kappaB suppression and HO-1 induction.
Animals ; Arthritis ; Cell Survival ; China ; Diabetes Mellitus ; Heme ; Heme Oxygenase-1 ; I-kappa B Proteins ; JNK Mitogen-Activated Protein Kinases ; Kalopanax ; Korea ; Macrophages ; Medicine, Traditional ; Mice ; NF-kappa B ; Nitric Oxide Synthase ; Phosphorylation ; Phosphotransferases

Microglial activation plays an important role in the development and progression of various neurological disorders such as cerebral ischemia, multiple sclerosis, and Alzheimer's disease. Thus, controlling microglial activation can serve as a promising therapeutic strategy for such brain diseases. In the present study, we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-alpha expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-inflammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-kappaB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-inflammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinflammatory cytokine gene expression via modulating NF-kappaB/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-inflammatory effects of kalopanaxsaponin A in LPS-stimulated microglia.
Alzheimer Disease ; Brain Diseases ; Brain Ischemia ; Cyclooxygenase 2 ; DNA ; Gene Expression ; Interleukins ; Kalopanax ; MAP Kinase Signaling System ; Microglia* ; Multiple Sclerosis ; Nervous System Diseases ; NF-kappa B ; Nitric Oxide Synthase Type II ; Phosphorylation ; Phosphotransferases ; Saponins ; Transcription Factor AP-1 ; Tumor Necrosis Factor-alpha ; Up-Regulation