Yoonjin Nam

Inhibitory Effects of ECQ on Indomethacin-Induced Gastric Damage in Rats

We investigated inhibitory effects of extract containing quercetin-3-O-β-D-glucuronopyranoside (ECQ) extracted from Rumex Aquaticus Herba on indomethacin-induced gastric damage in Rats. Gastritis was induced in male Sprague-Dawley rats (200~220 g) by oral administration of indomethacin at a dose of 40 mg/kg. One hour before administration of indomethacin, animals were orally pretreated with ECQ at doses of 0.3, 1, 3 or 10 mg/kg. Six hours after indomethacin administration, the rats were sacrificed and the stomach was excised and opened along the greater curvature, and the surface area of gastric lesion was measured using optical microscope. Superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) activities and malondialdehyde (MDA) levels were measured by ELISA. Western blot analysis was performed to detect protein expression of SOD-2. Linear hemorrhagic mucosal lesions were observed in the stomach 6 hours after oral administration of indomethacin. Pretreatment with ECQ significantly reduced the severity of the lesions in a dose-dependent manner. It also inhibited the reductions in SOD and CAT activities and SOD expression by the indomethacin-induced gastric damage. In addition, the pretreatment with ECQ significantly suppressed the elevation of the MPO activity and the MDA levels induced by indomethacin. These results suggest that ECQ has the inhibitory effects via antioxidative action against indomethacin-induced gastritis in rats.

The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells

Serotonin, or 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter found in blood platelets, the gastrointestinal (GI) tract, and the central nervous system (CNS) of animals and humans. The signaling pathways of 5-hydroxytryptamine (5-HT)-induced contractions in cat esophageal smooth muscle cell (ESMC)s have been identified, but the downstream components of the 5-HT signaling pathway remain unclear. DA-9701 is the standardized extract of the Pharbitis nil Choisy seed (Pharbitidis Semen, Convolvulaceae) and the root of Corydalis yahusuo W.T. Wang (Corydalis Tuber, Papaveraceae). DA-9701 is known to have strong gastroprokinetic effects and a good safety profile. In this study, we investigated the 5-HT signaling pathway at the G-protein level, and we explored the mechanisms by which DA-9701 induces smooth muscle contraction. Freshly isolated smooth muscle cells were harvested from the feline esophagus, and cells were permeabilized to measure their length. 5-HT produced esophageal smooth muscle contractions in a dose-dependent manner. Furthermore, 5-HT produced a relatively long-acting contraction. 5-HT binds to the 5-HT2, 5-HT3 and 5-HT4 receptors to induce smooth muscle contraction in feline ESMCs. These receptors, which are located in esophageal smooth muscle, are coupled to Gαq, Gαo and Gαs. These G proteins activate PLC, which leads to Ca2+/calmodulin-dependent MLCK activation, resulting in MLC20 phosphorylation and cell contraction. Conversely, DA-9701 inhibits 5-HT-induced contraction by inhibiting MLC20 phosphorylation.

The effect of Flos Lonicerae Japonicae extract on gastro-intestinal motility function

ETHNOPHARMACOLOGICAL RELEVANCE Flos Lonicerae Japonicae is a well-known herb of traditional Chinese medicine that has been used for heat-clearing, detoxification, anti-inflammation, throat pain and gastro-intestinal (GI) disorder. In order to verify the effect of Flos Lonicerae Japonicae on GI disorder, we investigated the prokinetic effect of GC-7101 on GI motility function. MATERIALS AND METHODS GC-7101 is the standardized extract of Flos Lonicerae Japonicae. The contractile action of GC-7101 on feline esophageal smooth muscle cell (ESMC) was evaluated by measuring dispersed cell length. The isometric tension study was performed to investigate the effect of GC-7101 on feline lower esophageal sphincther (LES). The prokinetic effect of GC-7101 was investigated by gastric emptying (GE) and gastro-intestinal transit (GIT) in rats. RESULTS GC-7101 produced concentration-dependent contractions in ESMCs. Pretreatment with 5-HT3 and 5-HT4 receptor blocker (ondansetron and GR113808) inhibited the contractile responses of the GC-7101-induced ESMCs. In isometric tension study, GC-7101 recovered the HCl-induced decreased tone of LES muscle strips. The treatment of GC-7101 enhanced the carbachol-induced contractile responses and the electric field stimulation (EFS)-induced on-contraction. The oral administration of GC-7101 not only significantly accelerated GE and GIT in normal rats but also recovered the delayed GE and GIT, and its effect was more potent than that of conventional prokinetics (e.g., domperidone, a dopamine-receptor antagonist, and mosapride, a 5-HT4-receptor agonist). CONCLUSION GC-7101 revealed a prokinetic effect through enhancing the contractile responses of ESMCs, tone increases, enhancing the carbarchol- or EFS-induced contractile responses of LES muscle strips, and the acceleration of GE and GIT. We have identified the significant potential of GC-7101 for the development of new prokinetic drugs through this study.

Effect of ECQ on Iodoacetamide-Induced Chronic Gastritis in Rats

This study investigated effect of extract containing quercetin-3-O-β-D-glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation.

Gastroprotective Effect of the Three Glucuronopyranoside Flavonoids in Rats

In this study, we investigated the protective action of glucuronopyranoside flavonoids (QGC, AGC, LGC) on gastritis in rats. QGC, AGC and omeprazole decreased the gastric volume significantly, and each ID50 was 0.75, 0.54 and 8.5 mg/kg, respectively, thus the order of potency was AGC, QGC and omeprazole. They also decreased acid output, and each ID50 was 7.81, 0.58 and 6.71 mg/kg, respectively, thus the order of potency was AGC, omeprazole and QGC. They inhibited gastritis induced by indomethacin, and it recovered significantly by increasing the GSH levels in gastritis. The gastric MPO activity in the gastritis group increased more than in the normal group. QGC, LGC, or AGC administration reduced moderately the MPO activity in a dose-dependent manner. This study demonstrated that AGC, QGC, or LGC showed potent efficacy on the gastritis, by preventing oxidative stress. These results suggest that QGC, AGC, or LGC have gastroprotective effect in rats.

Protective effect of ultrasonication-processed ginseng berry extract on the D-galactosamine/lipopolysaccharide-induced liver injury model in rats

Background Acute hepatic failure is a life-threatening critical condition associated with rapid deterioration of liver function and liver transplantation. Several studies have shown that Panax ginseng Mayer has antidiabetic and hepatoprotective effects. However, the hepatoprotective effect of ginseng berry is still unveiled. In this study, we evaluated the hepatoprotective effects of ultrasonication-processed ginseng berry extract (UGBE) on acute hepatic failure model in rats. Methods Ginseng berry extract (GBE) was ultrasonically processed. The GBE, silymarin, and UGBE were orally administered to male Sprague-Dawley rats for 4 wk. Twenty-four h after the last administration, rats were challenged with D-galactosamine (D-GalN)/lipopolysaccharide (LPS). Results After ultrasonication, the component ratio of ginsenosides Rg2, Rg3, Rh1, Rh4, Rk1, Rk3, and F4 in GBE had been elevated. Administration of UGBE significantly increased the survival rate of D-GalN/LPS-challenged rats. Pretreatment with UGBE significantly decreased serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in D-GalN/LPS-challenged rats in a dose-dependent manner. The levels of enzymatic markers for oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and glutathione) were increased by UGBE treatment in a dose-dependent manner. Tumor necrosis factor alphalevel, inducible nitric oxide synthase activities, and nitric oxide productions were reduced by UGBE treatment. In addition, hemeoxygenase-1 levels in liver were also significantly increased in the UGBE-treated group. The protein expression of toll-like receptor 4 was decreased by UGBE administration. Hematoxylin and eosin staining results also supported the results of this study showing normal appearance of liver histopathology in the UGBE-treated group. Conclusion UGBE showed a great hepatoprotective effect on D-GalN/LPS-challenged rats via the toll-like receptor 4 signaling pathway.

The change of signaling pathway on the electrical stimulated contraction in streptozotocin-induced bladder dysfunction of rats

Bladder dysfunction is a common complication of diabetes mellitus (DM). However, there have been a few studies evaluating bladder smooth muscle contraction in DM in the presence of pharmacological inhibitors. In the present study, we compared the contractility of bladder smooth muscle from normal rats and DM rats. Furthermore, we utilized pharmacological inhibitors to delineate the mechanisms underlying bladder muscle differences between normal and DM rats. DM was established in 14 days after using a single injection of streptozotocin (65 mg/kg, intraperitoneal) in Sprague-Dawley rats. Bladder smooth muscle contraction was induced electrically using electrical field stimulation consisting of pulse trains at an amplitude of 40 V and pulse duration of 1 ms at frequencies of 2–10 Hz. In this study, the pharmacological inhibitors atropine (muscarinic receptor antagonist), U73122 (phospholipase C inhibitor), DPCPX (adenosine A1 receptor antagonist), udenafil (PDE5 inhibitor), prazosin (α1-receptor antagonist), verapamil (calcium channel blocker), and chelerythrine (protein kinase C inhibitor) were used to pretreat bladder smooth muscles. It was found that the contractility of bladder smooth muscles from DM rats was lower than that of normal rats. In addition, there were significant differences in percent change of contractility between normal and DM rats following pretreatment with prazosin, udenafil, verapamil, and U73122. In conclusion, we suggest that the decreased bladder muscle contractility in DM rats was a result of perturbations in PLC/IP3-mediated intracellular Ca2+ release and PDE5 activity.

Humulus japonicus Extracts Protect Against Lipopolysaccharide/d-Galactosamine-Induced Acute Liver Injury in Rats

It has been described that Humulus japonicus has potential antituberculosis and anti-inflammatory effects. The antiaging activity of H. japonicus extract (HJE) was also examined not only in yeast but also in human fibroblast cells. We evaluated the protective effect of HJE on hepatotoxicity in this study. We demonstrated the expression of antioxidative enzyme and cytokines in plasma. The vehicle control group received orally administered normal saline. Acute hepatotoxicity rat model was induced by lipopolysaccharide (LPS) (30 μg/kg) and d-galactosamine (D-GalN) (500 mg/kg) by intraperitoneal injection. The positive control group received orally administered silymarin (10 mg/kg). Three HJE groups received 8, 16, and 32 mg/kg. The blood samples were prepared to evaluate malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) level to examine oxidative stress, and hepatic tissue was assayed for myeloperoxidase (MPO). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-α (TNF-α) activities were also assayed to examine liver cell viability. Pretreatment with HJE decreased levels of AST, ALT, MDA, MPO, and TNF-α and increased levels of SOD and CAT compared with the LPS/D-GalN-treated group. These results suggested that HJE has the potential to reduce oxidative damage and inflammatory reactions in LPS/D-GalN-induced liver injury in the rat model. It can also increase survival rate in LPS/D-GalN-induced hepatotoxicity rat models.

Hepatoprotective effect of ultrasonicated ginseng berry extract on a rat mild bile duct ligation model

Background The Panax ginseng berry extract (GBE) is well known to have an antidiabetic effect. The aim of this study is to evaluate and investigate the protective effect of ultrasonication-processed P. ginseng berry extract (UGBE) compared with GBE on liver fibrosis induced by mild bile duct ligation (MBDL) model in rats. After ultrasonication process, the composition ratio of ginsenoside in GBE was changed. The component ratio of ginsenosides Rh1, Rh4, Rg2, Rg3, Rk1, Rk3, and F4 in the extract was elevated. Methods In this study, the protective effect of the newly developed UGBE was evaluated on hepatotoxicity and neuronal damage in MBDL model. Silymarin (150 mg/kg) was used for positive control. UGBE (100 mg/kg, 250 mg/kg, 500 mg/kg), GBE (250 mg/kg), and silymarin (150 mg/kg) were orally administered for 6 weeks after MBDL surgery. Results The MBDL surgery induced severe hepatotoxicity that leads to liver inflammation in rats. Also, the serum ammonia level was increased by MBDL surgery. However, the liver dysfunction of MBDL surgery–operated rats was attenuated by UGBE treatment via myeloid differentiation factor 88-dependent Toll-like receptor 4 signaling pathways. Conclusion UGBE has a protective effect on liver fibrosis induced by MBDL in rats through inhibition of the TLR4 signaling pathway in liver.

Recent advances in pharmacological research on the management of irritable bowel syndrome

Irritable bowel syndrome (IBS), a common gastrointestinal (GI) disorder, is associated with various factors, including lifestyle, infection, stress, intestinal flora, and related diseases. The pharmacotherapeutic stimulation of receptors and downstream signaling pathways is effective in reducing IBS symptoms; however, it is still associated with adverse effects. Various receptors related to GI motility and visceral hypersensitivity should be considered to enhance the benefit/risk ratio of IBS treatments. This review discusses recent pharmacological advances in IBS management. Several receptors related to GI motility and abdominal pain are investigated in various angles. 5-Hydroxytryptamine (5-HT) is an important neurotransmitter that activates the colonic mucosal 5-HT4 receptor without causing severe cardiovascular adverse effects. The clinical potential of ramosetron for diarrhea-predominant IBS has been suggested because of a lower risk of ischemic colitis than conventional 5-HT3 receptor antagonists. Toll-like receptors (TLRs), especially TLR2 and TLR4, show a significant effect on the post-infection symptoms and lipopolysaccharide-mediated regulation of GI motility. Histamine is a well-known nitrogenous compound that regulates inflammatory responses and visceral hypersensitivity. Histamine 1 receptor-mediated sensitization of the transient receptor potential vanilloid 1 is associated with IBS. Pharmacological approaches based on these signaling pathways could be useful in the development of novel IBS treatments.