• Journal of Ginseng Research
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• 제22권1호
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• pp.22-31
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• 1998

Antiulcer effects of ginseng saponin, acidic polysaccharide and methanol extract of Panax ginseng in the patients and experimental animals were reported. Postulated action mechanisms of ginseng were histamine-Ht receptor blocking and increasing gastric blood flow In the present study, the effect of ginsenosides, the biologically active glycosides of ginseng, on gastric acid secretion was examined using gastric cells isolated from human and rabbit gastric mucosa. Ginseng saponin, ginsenoside $Rb_1$, $Rb_2$, $Rg_1$ and $Rh_2$ were tested in unstimulated as well as stimulated gastric cells. Histamine ($10^4$M) and 3-isobutyl-1-methylxanthine ($10^4$M) were used as secretagogues. To investigate the mechanism of ginsenosides on acid secretion, the levels of cAMP and cGMP were monitored in gastric cells. As a result, high concerltration(1mg/ml) of ginseng saponin showed 73-75% of stimulated acid secretion in control gastric cells. However, ginseng saponin had no effect on unstimulated acid secretion and the levels of cGMP and cAMP in gastric cells. Ginsenoside $Rb_1$, $Rb_2$ and $Rh_2$ significantly inhibited stimulated acid secretion. Gastric cGMP levels were increased by all ginsenosides tested while cAMP levels were increased by all ginsenosides in unstimulated state of gastric cells, but increased by ginsenosides ginsenoside $Rg_1$ and $Rh_2$in stimulated state of gastric cells. The results suggest that inhibition of ginseng saponin on gastric acid secretion represents a complex effect of individual ginsenosides, which produce a range of effect on acid secretion. The inhibition site of ginseng saponin on stimulated acid secretion is postulated as post cAMP levels in acid secretary pathway such as protein phosphorylation or proton pump. Nitric oxide may not be involved in the inhibitory effect of ginseng saponin on stimulated acid secretion.

• Biomolecules & Therapeutics
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• 제4권2호
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• pp.111-121
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• 1996

Antiulcer effects of Artemisia herba extract (DA-9601) were evaluated in various types of experimental gastric ulcer induced in rats. And the effects of DA-9601 on mucus, basal and stimulated gastric acid secretion were also investigated in rats. DA-9601 (12.5∼400 mg/kg, p.o.) prevented the formation of gastric ulcers induced by 60% EtOH in 150 mM HC1, restraint water immersion stress, platelet activating factor (PAF), aspirin in 150 mM HCI with Pylorus-ligation and indomethacin. DA-9601 (4∼400 mg/kg, p.o.) significantly accelerated the healing rate of acetic acid-induced gastric ulcer and significantly stimulated mucus secretion in a dose-dependent manner. DA-9601 (20∼200 mg/kg, i.d.), however, did not inhibit basal gastric acid secretion in pylorus ligated rats and DA-9601 (200 mg/kg, i.d.) failed to influence histamine-, pentagastrin- and carbachol- stimulated gastric acid secretion. These results suggest that DA-9601 has inhibitory action on gastric lesion and ulceration through increasing mucus secretion in the stomach of rats without influencing basal and stimulated gastric acid secretion.

• Archives of Pharmacal Research
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• 제12권4호
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• pp.243-248
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• 1989

Effects of B-HT 920 on the vagally stimulated gastric acid secretion were studied in anesthetized and gastric fistula rats. When the gastric acid secretion was increased by stimulation of the vagus nerve, B-HT 920 was partially attenuated by prazosin, $\alpha_1-$adrenoceptor antagonist and virtually abolished by yohimbine, $\alpha_2-$adrenoceptor antagonist. On the other hand, when the gastric acid secretion was increased by the infusion of bethanechol, a muscarinic parasympathetic stimulant, B-HT 920 had no effect on the bethanechol-induced gastric acid secretion. These results suggest that B-HT 920 inhibits vagally induced gastric acid secretion by activation of presynaptic $\alpha-$adrenoceptors located on the vagally stimulated pathways in the gastric wall and this effect of B-HT 920 is more related to $\alpha_2-$adrenoceptors than $\alpha_1-$adrenoceptors.

• 대한약리학회지
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• 제31권1호
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• pp.75-84
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• 1995

NO의 위산분비에 대한 작용을 규명하기 위하여 분리한 토끼위선세포에서 hypoxia/reoxygenation과 acidosis후 위산분비와 NO synthase 활성을 측정하였다. 분리한 위선세포에 30분의 hypoxia와 1시간의 reoxygenation을 주었으며, acidosis를 위하여 배지의 pH를 6.0과 4.0으로 변화시켜 실험하였다. 위산분비는 위선세포 내와 외의 $[^{14}C]-aminopyrine$ 축적비율로 측정하였으며, NO synthase 활성은 NO의 전구물질인 $[^{14}C]L-arginine$으로부터 $[^{14}C]-citrulline$으로의 전환율로 결정하였다. 결과로서 dibutyryl cAMP는 농도 의존적으로 위산분비를 촉진시켰으나 NO synthase 활성엔 영향을 주지 않았다. Hypoxia/reoxygenation은 기초 및 자극 위산분비를 억제하였으며 acidosis에 의해 위산분비억제는 더욱 심화되었다. Constitutive NO synthase 활성 역시 hypoxia/reoxygenation과 acidosis에 의해 억제되었다. 결론적으로 hypoxia/reoxygenation과 acidosis 같은 위점막의 병적상태는 위산분비와 NO 유리를 모두 억제하나, 기초상태의 위선에서 dibutyryl cAMP에 의한 위산분비 촉진에 대한 NO의 직접적인 작용은 확인되지 않았다.

• The Korean Journal of Physiology
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• 제23권1호
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• pp.119-127
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• 1989

This study was undertaken to investigate the effect of medial amygdala on the gastric acid secretion and plasma gastrin concentration in the rats with chronic gastric fistula. After the medial nucleus of amygdala was damaged bilaterally by radiofrequency a. c. through stereotaxically inserted electrodes, the gastric juice was collected in the basal and histamine-stimulated states for 1 hour. The gastric juice was also collected while the medial nucleus of amygdala was stimulated with biphasic square wave in the both states. After the collection of the gastric juice, blood samples were drawn from the abdominal aorta for the radioimmunoassay of plasma gastrin. The results were as follows: 1) The damage of the medial amygdala significantly decreased the gastric juice volume and the acid output in the histamine-stimulated state. 2) The electrical stimulation of the medial amygdala significantly increased the gastric juice volume and the acid output in the histamine-stimulated state, and the acid output in the basal state. 3) The damage of the medial amygdala significantly decreased the plasma gastrin concentration but the electrical stimulation of the medial amygdala did not affect the plasma gastrin concentration. It is therefore suggested that the medial amygdala has a facilitatory influence on the histamine-stimulated gastric acid secretion in rats, and the influence may not be attributed to gastrin release.

• 대한약리학회지
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• 제12권1호
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• pp.57-62
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• 1976

Using modified technique of Schmidt et al, as described previously (Korean J. Pharmacol 9 : 17, 1973), the stomach of female rats were perfused with physiological saline under urethane anesthesia. The acid-secretory response of the perfused stomach to i.v. hypertonic glucose (50%), casein hydrolysate (20%) or saline (6%) solution were studied with or without histamine or methacholine stimulation. A significant decrease of acid secretion from the rat stomach was induced by i.v. hypertonic glucose or saline solution. The histamine-stimulated acid secretion was also decreased by simultaneous administration of the hypertonic glucose or saline. However, methacholine-stimulated acid response was not affected by the hypertonic glucose. Intravenous infusion of 20% casein hydrolysate solution resulted in an increase in acid output from the stomach under histamine stimuli. These results lead to the conclusion that the inhibitory responses of acid secretion due to i.v. hypertonic glucose solution are brought through the effect of histaminergic, not cholnergic mechanism(s) in the gastric secretion.

• 동의신경정신과학회지
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• 제12권2호
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• pp.157-171
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• 2001

Astrocytes are glial cells that play a major role in the inflammation observed in Alzheimer's disease (AD). Upon stimulation from various agents, these cells adopt a reactive phenotype, a morphological hallmark in AD pathology, during which they themselves may produce still more inflammatory cytokines. Substance P (SP) can stimulate secretion of tumor necrosis $factor-\;{\alpha}$ $(TNF-\;{\alpha})$ from astrocytes stimulated with lipopolysaccharide (LPS). Here I report that Sunghyangjungkisan- ga- pogokyoung(Sgp) can modulate cytokines secretion from primary cultures of rat astrocytes. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with LPS and SP. Interleukin-1 (IL-1) has been shown to elevate $TNF-\;{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Treatment of Sgp $(10\;to\;1000\;{\mu}g/ml)$ to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of $TNF-\;{\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Neurodegenerative processes in AD are thought to be driven in part by the deposition of ${\beta}\;-amyloid\;(A\;{\beta})$, a 39- to 43-amino acid peptide product resulting from an alternative cleavage of amyloid precursor protein. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with $A-{\beta}-$and IL-1. These results suggest that Sgp may inhibit $TNF-\;{\alpha}$ secretion by inhibiting IL-1 secretion and that Sgp has an antiinflammatory activity in AD brain

• Journal of Dairy Science and Biotechnology
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• 제29권2호
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• pp.17-23
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• 2011

The focus of this study was to clarify the relation between the nitric oxide (NO) production and cytokine expression including tumor necrosis factor-${\alpha}$ (TNF) and interleukin-6 (IL-6), and also investigated the effect of G-NANA (N-acylneuraminic acid isolates from glycomacropeptide) or S-NANA (Synthetic N-acylneuraminic acid) on LPS stimuli from RAW264.7 cell. The NANA is the predominant sialic acid found in mammalian cells and G-NANA is isolation of GMP (GMP is a valuable bioactive peptide with a varying degree of glycosylation including sialic acid). The lipopolysaccharide (LPS) of Gram-negative bacteria induces the expression of cytokines and potent inducers of inflammatory cytokines such as TNF-${\alpha}$ and IL-6. In this experiment, upon stimulation with increasing concentrations of chitosan, the LPS-stimulated TNF-${\alpha}$ and IL-6 secretion was significantly recovered with in the incubation media of RAW264.7 cells. Consistently, RT-PCR with mRNA and immunoblot analysis with anti-cytokine antiserum including TNF-${\alpha}$ and IL-6 showed that the amount of TNF-${\alpha}$ and IL-6 secretion in the incubation media recovered with the concentration of chitosan. The LPS-stimulated NO secretion was significantly recovered with in the 6 and 12 h incubation media of RAW264.7 cells, too. The recovery effect of G-NANA on IL-6 and NO secretion may be induced via the stimulus of TNF-${\alpha}$ in RAW264.7 cell. These results once again suggest that G-NANA may have the anti-inflammatory effect via the stimulus of TNF-${\alpha}$ in the LPS-stimulated inflammation in RAW264.7 cells.

• Journal of Ginseng Research
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• 제47권4호
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• pp.572-582
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• 2023

Background: Free fatty acid-induced lipotoxicity is considered to play an important role in pancreatic β-cell dysfunction. The effect of ginsenosides on palmitic acid-induced pancreatic beta-cells cell death and failure of glucose-stimulated secretion of insulin (GSIS) was evaluated in this study. Methods: Enzyme-linked immunosorbent assay kit for a rat insulin was used to quantify glucose-stimulated insulin secretion. Protein expression was examined by western blotting analysis. Nuclear condensation was measured by staining with Hoechst 33342 stain. Apoptotic cell death was assessed by staining with Annexin V. Oil Red O staining was used to measure lipid accumulation. Results: We screened ginsenosides to prevent palmitic acid-induced cell death and impairment of GSIS in INS-1 pancreatic β-cells and identified protopanaxadiol (PPD) as a potential therapeutic agent. The protection effect of PPD was likely due to a reduction in apoptosis and lipid accumulation. PPD attenuated the palmitic acid-induced increase in the levels of B-cell lymphoma-2-associated X/B-cell lymphoma 2, poly (ADP-ribose) polymerase and cleaved caspase-3. Moreover, PPD prevented palmitic acid-induced impairment of insulin secretion, which was accompanied by an increase in the activation of phosphatidylinositol 3-kinase, peroxisome proliferator-activated receptor γ, insulin receptor substrate-2, serine-threonine kinase, and pancreatic and duodenal homeobox-1. Conclusion: Our results suggest that the protective effect of PPD on lipotoxicity and lipid accumulation induced by palmitic acid in pancreatic β-cells.

• The Korean Journal of Physiology
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• 제20권2호
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• pp.249-256
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• 1986

The present study was performed to investigate a possible influence of the adrenergic nervous system on pancreatic exocrine secretion stimulated by intraduodenal acid perfusion. Pancreatic secretion was collected in rats anesthetized with urethane after 24 hours fasting. The duodenal lumen was perfused (0.2 ml/min) with HCI solution in a concentration of 0.005, 0.01, 0.02, 0.05 or 0.1 N When the volume of panceratic juice secreted for IS min became constant phentolamine (1 mg/kg), $noradrenaline\;(10\;{\mu}g/kg),\;Propranolol\;(1\;mg/kg),\;and \;isoproterenol\;(1\;{\mu}g/kg)$ were administered through the jugular vein in bolus. The secretory volume and protein output were measured in the pancreatic juice collected for 15 min. 1) HCI, perfused intraduodenally in graded concentrations from 0.005 N to 0.1 N, increased the pancreatic secretory volume and protein output dose-dependently. 2) In the basal state as well as in the stimulated state by the duodenal acid perfusion, phentolamine increased the pancreatic secretory volume and protein output while propranolol inhibited the volume and protein output. 3) In the basal state, noradrenaline did not change the pancreatic secretory volume but increased the protein output while isoproterenol increased both of the secretory volume and the protein output. These results strongly suggest that ${\alpha}-adrenoceptors$ in the rat pancreas exert an inhibitory influence on the pancreatic exocrine secretion including volume and protein output in the basal state as well as in the stimulated state by the intraduodenal acid perfusion while ${\beta}-adrenoceptors$ play a stimulatory role in the pancreatic exocrine secretion. However, in the physiological situation, adrenergic excitation may stimulate the protein output through ${\beta}-adrenoceptors$ without change in the secretory volume in the rat pancreas.