Choon Sik Jeong

Anti-inflammatory mechanisms of apigenin: inhibition of cyclooxygenase-2 expression, adhesion of monocytes to human umbilical vein endothelial cells, and expression of cellular adhesion molecules.

The aim of this study was to clarify the anti-inflammatory mechanism of apigenin. Apigenin inhibited the collagenase activity involved in rheumatoid arthritis (RA) and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a dose dependent manner in RAW 264.7 macrophage cells. Pretreatment with apigenin also attenuated LPS-induced cyclooxygenase-2 (COX-2) expression. In addition, apigenin profoundly reduced the tumor necrosis factor-a (TNF-a)-induced adhesion of monocytes to HUVEC monolayer. Apigenin significantly suppressed the TNF-a-stimulated upregulation of vascular cellular adhesion mole-cule-1 (VCAM-1)-, intracellular adhesion molecule-1 (ICAM-1)-, and E-selectin-mRNA to the basal levels. Taken together, these results suggest that apigenin has significant anti-inflammatory activity that involves blocking NO-mediated COX-2 expression and monocyte adherence. These results further suggest that apigenin may be useful for therapeutic management of inflammatory diseases.

Mechanism of apoptosis induced by apigenin in HepG2 human hepatoma cells: involvement of reactive oxygen species generated by NADPH oxidase.

Although plant-derived flavonoids have been reported to have anti-cancer activities, the exact mechanism of these actions is not completely understood. In this study we investigated the role for reactive oxygen species (ROS) as a mediator of the apoptosis induced by apigenin, a widespread flavonoid in plant, in HepG2 human hepatoma cells. Apigenin reduced cell viability, and induced apoptotic cell death in a dose-dependent manner. In addition, it evoked a dose-related elevation of intracellular ROS level. Treatment with various inhibitors of the NADPH oxidase (diphenylene iodonium, apocynin, neöpterine) significantly blunted both the generation of ROS and induction of apoptosis induced by apigenin. These results suggest that ROS generated through the activation of the NADPH oxidase may play an essential role in the apoptosis induced by apigenin in HepG2 cells. These results further suggest that apigenin may be valuable for the therapeutic management of human hepatomas.

Protective effects of neohesperidin and poncirin isolated from the fruits of Poncirus trifoliata on potential gastric disease.

The effects of Poncirus trifoliata (P. trifoliata) (Ponciri Fructus, PF) extract and its constituents such as neohesperidin and poncirin on gastritis in rats and human gastric cancer cells were investigated. The PF 70% ethanol extracts (1 g) showed approximately 11.38% of acid‐neutralizing capacities and cytotoxicity (IC50 = 85.39 µg/mL) against human AGS gastric cancer cells. In addition, neohesperidin exhibited antioxidant activity (IC50 = 22.31 µg/mL) in the 1,1‐diphenyl‐2‐picryldydrazyl (DPPH) radical‐scavenging assay. Neohesperidin (50 mg/kg) and poncirin (100 mg/kg) significantly inhibited 55.0% and 60.0% of HCl/ethanol‐induced gastric lesions, respectively, and increased the mucus content. In pylorus ligated rats, neohesperidin (50 mg/kg) significantly decreased the volume of gastric secretion and gastric acid output, and increased the pH. From these results, it could be suggested that neohesperidin and poncirin isolated from PF may be useful for the treatment and/or protection of gastritis. Copyright

Isolation and tandem mass fragmentations of an anti-inflammatory compound from Aralia elata

One-step isolation of a saponin from Aralia elata was undertaken using high-speed countercurrent chromatography coupled with evaporative light scattering detection. A triterpenoid saponin, elatoside F, was purified with 96.8% purity using a two-phase-system comprising chloroform-methanol-water-isopropanol. The yield was 35.0 mg from 348.2 mg of the enriched saponin fraction. In vitro anti-inflammatory study demonstrated that elatoside F inhibited lipopolysaccharide-induced nitric oxide production, as well as nuclear factor κB activation, in a dose-dependent manner. Two types of mass ionization technique were compared on elatoside F to investigate characteristic fragmentation patterns. MALDI-TOF tandem mass spectrometric fragmentation patterns of sodiated ions provided structural information on glycosidic cleavages and on extensive cross-ring cleavages. Electrospray ionization multiple-stage tandem mass fragmentation of both sodiated and lithiated ions could provide information on glycosidic cleavages. All observed tandem mass fragmentation spectra provided valuable elatoside F structural information when unknown samples from crude extracts are under screening by mass spectrometry.

Effect of butanol fraction of Panax ginseng head on gastric lesion and ulcer.

From our previous result thatPanax ginseng head extract had inhibition of gastric damages, the extract was fractionated. Among the hexane, chloroform, butanol and water fractions, butanol fraction showed the most potent inhibition of HCI ethanol-induced gastric lesion, aspirin-induced gastric ulcer, acetic acid-induced ulcer and Shay ulcer. Butanol fraction showed significant increase in mucin secretion, and inhibited malondialdehyde (MDA) and H+/ K+ATPase activity in the stomach. This results indicate that the effectiveness of the fraction on gastric damages might be related to inhibition of acid secretion, increment of mucin secretion and antioxidant property.

Effects of constituents of amomum xanthioides on gastritis in rats and on growth of gastric cancer cells

In this study we investigated the effects of constituents of Amomum xanthioides (AX) on gastritis in rats and on the growth of human gastric cancer cells. The ethanol extract of Amomum xanthioides significantly inhibited HCl ° ethanol-induced gastric lesions and the growth of Helicobacter pylori (H. pylori). The ethanol extract of AX was further fractionated with hexane, chloroform, butanol and H2O. Among these fractions, oral treatment with the butanol fraction at a dose of 350 mg/kg was the most effective at preventing HCl ° ethanol-induced gastric lesions. In pylorus ligated rats, the butanol fraction also decreased the volume of gastric secretion and gastric acid output. We isolated six subfractions of the butanol fraction using open column chromatography. Subfraction 4 (150 mg/kg) significantly inhibited HCl ° ethanol-induced gastric lesions and gastric secretion in pylorus ligated rats. Using GC-MS we identified the constituents of subfraction 4 to be five aliphatic compounds, 1-hexadecene, 1-nonadecene, cycloeicosane, 1-octadecene and cyclotetracosane. In addition, subfraction 4 reduced cell viability in a dose-dependent manner in human gastric cancer cells (AGS, KATOIII and SNU638). It also increased intracellular Ca2+ concentration in SNU638 cells, an effect that was significantly inhibited by dantrolene, a Ca2+ release blocker. Moreover, dantrolene significantly inhibited subfraction 4-induced cytotoxicity. Taken together, these results suggest that subfraction 4 of the butanol extract of AX has an anti-gastritic effect in rats and is cytotoxic to human gastric cancer cells. The mechanism of its anti-gastritic action may be associated with the inhibition of secretion of gastric acid and anti-H. pylori action. Its cytotoxicity against human gastric cancer cells may be, at least in part, mediated by intracellular Ca2+ dyshomeostasis. From these results, we suggest that AX may be useful for the treatment of gastritis and gastric cancer.

Suppressive effects on the biosynthesis of inflammatory mediators by Aralia elata extract fractions in macrophage cells.

The aim of this study is to elucidate the anti-inflammatory effects of Aralia elata extract fractions (AEEFs). A. elata-ethyl acetate fraction (AEEF) had the strongest antioxidant activity. A. elata-chloroform fraction (AECF) and A. elata-butanol fraction (AEBF) inhibited potently LPS-induced nitrite production from RAW 264.7 macrophage cells. The inhibition of nitric oxide (NO) production by AEEFs was partially due to chemical scavenge of NO and the suppression of inducible NOS (iNOS) transcription level in LPS-induced macrophage cells. In addition, AEEFs inhibited significantly the biosynthesis of Prostaglandin E(2) (PGE(2)), and cyclooxygenase-2, which regulates the synthesis of PGE(2), was attenuated partially by the treatment of AEEFs in LPS-induced macrophage cells. Also, A. elata-methanolic extract (AEME) suppressed remarkably IL-1β and IL-6 level to the basal (more than 99% inhibition) in concentration-dependant manners. Its anti-inflammatory actions might be related with inhibition of NF-κB activation in LPS-stimulated macrophage cells. It is concluded that AEEFs may be useful as a functional food material and an alternative medicine for the relief and retardation of immunological inflammatory responses.

Protective Effect of Liriodendrin Isolated from Kalopanax pictus against Gastric Injury

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 μM. It was also exhibited acid-neutralizing capacity (10.3%) and H+/K+-ATPase inhibition of 42.6% (500 μM). 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.

Protective Effects of Genipin on Gastrointestinal Disorders

Genipin, an aglycone of geniposide, is a major component of gardeniae fructus, and has been used to treat jaundice, various inflammatory disorders, and liver disease, and has also been used as a natural cross-linking agent. The authors conducted several experiments to evaluate the protective effects of genipin on gastrointestinal disorders, such as, gastritis and gastric ulcers. Genipin showed inhibitory effects against HCl·ethanol-induced acute gastritis and indomethacin-induced gastric ulcers in rats and increased prostaglandin E2 (PGE2) in AGS gastric cancer cell. Genipin had significant effects on aggressive factors, acid-neutralization, and gastric secretion, and inhibited H+/K+-ATPase (a proton pump), which secretes gastric acid. The results obtained indicate that genipin has significant gastroprotective effects and might be useful for treating and preventing gastric lesions.

Gastroprotective Activities of Sennoside A and Sennoside B via the Up-Regulation of Prostaglandin E2 and the Inhibition of H(+)/K(+)-ATPase.

Sennoside A (erythro) and sennoside B (threo) are dianthrone glycosides and diastereomers. We investigated their abilities to prevent the gastric lesions associated with diseases, such as, gastritis and gastric ulcer. To elucidate their gastroprotective effects, the inhibitions of HCl•EtOH-induced gastritis and indomethacin-induced gastric ulcers were assessed in rats. It was observed that both sennoside A and sennoside B increased prostaglandin E2 (PGE2) levels and inhibited H+/K+-ATPase (proton pump). In a rat model, both compounds reduced gastric juice, total acidity and increased pH, indicating that proton pump inhibition reduces gastric acid secretion. Furthermore, sennoside A and B increased PGE2 in a concentration-dependent manner. In a gastric emptying and intestinal transporting rate experiment, both sennoside A and sennoside B accelerated motility. Our results thus suggest that sennoside A and sennoside B possess significant gastroprotective activities and they might be useful for the treatment of gastric disease.