• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.835-842
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• 2016

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays a crucial role in cancer occurrence by promoting cell proliferation and inhibiting apoptosis. In the present study, we evaluated the effect of a PI3K inhibitor, LY294002, on the chemosensitivity of gastric cancer cells to cordycepin, a predominant functional component of the fungus Cordyceps militaris, in AGS human gastric cancer cells and investigated possible underlying cellular mechanisms. Our results revealed that cordycepin inhibited viability of AGS cells in a concentration-dependent manner and induced apoptosis, as determined by apoptotic cell morphologies and fluorescence-activated cell sorting analysis associated with attenuated activation of the PI3K/Akt signaling pathway. Treatment with cordycepin in combination with a subtoxic concentration of LY294002 enhanced cordycepin-induced cytotoxicity and apoptotic potentials in AGS cells. Sensitization of LY294002 to cordycepin-induced apoptosis was accompanied by activation of caspases (caspases-3, -8, and -9) and was concomitant with poly(ADP-ribose) polymerase cleavage. Moreover, LY294002 up-regulated pro-apoptotic Bax and enhanced truncation of Bid in cordycepin-treated AGS cells, which was connected with increased loss of mitochondrial membrane potential and release of cytochrome c from mitochondria to the cytosol. Taken together, these results indicate that inhibition of the PI3K/Akt signaling pathway could augment cordycepin-induced apoptosis in human gastric cancer cells by up-regulating caspase activity through mitochondrial dysfunction.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.655-663
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• 2020

Background: Korean Red Ginseng is known to exhibit immune-enhancing and anti-inflammatory properties. The immune-enhancing effects of the nonsaponin fraction (NSF) of Korean Red Ginseng have been studied in many reports. However, the gastroprotective effect of this fraction is not fully understood. In this study, we demonstrate the activities of NSF for gastrointestinal protection and its related critical factor. Methods: The in vitro and in vivo regulatory functions of NSF on cyclooxygenase-1 (COX-1) messenger RNA and protein levels were examined by reverse transcription polymerase chain reaction and immunoblotting analyses. Gastroprotective effects of NSF were investigated by histological score, gastric juice pH, and myeloperoxidase activity on indomethacin-induced, cold stress-induced, and acetylsalicylic acid-induced gastritis and dextran sulfate sodium-induced colitis in in vivo mouse models. Results: NSF did not show cytotoxicity, and it increased COX-1 messenger RNA expression and protein levels in RAW264.7 cells. This upregulation was also observed in colitis and gastritis in vivo models. In addition, NSF treatment in mice ameliorated the symptoms of gastrointestinal inflammation, including histological score, colon length, gastric juice pH, gastric wall thickness, and myeloperoxidase activity. Conclusion: These results suggest that NSF has gastroprotective effects on gastritis and colitis in in vivo mouse models through COX-1 upregulation.

• Korean Journal of Pharmacognosy
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• v.33 no.2 s.129
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• pp.151-155
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• 2002

Previously, we have reported that the butanol fraction of the head of Panax ginseng had significant gastroprotective activity on gastritis and gastric ulcer models of rats. Considering the safety of the fraction for development of new anti-ulcerative agent or food supplement, general pharmacological study was carried on. The fraction was revealed that have no influence on spontaneous activity, phenobarbital-induced sleeping time, rotarod test, body temperature, gastro-intestinal motility, respiration and blood pressure. The fraction showed weak analgesic action in writhing syndrome and did not show any sign of acute toxicity in mice.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5189-5193
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• 2016

Objective: Dorema glabrum Fisch. & C.A. Mey is a perennial plant that has several curative properties. Anti-proliferative activity of seeds of this plant has been demonstrated in a mouse fibrosarcoma cell line. The aim of the present study was to evaluate cytotoxicity of D. glabrum root extracts in a human gastric adenocarcinoma (AGS) cell line and explore mechanisms of apoptosis induction, cell cycle arrest and altered gene expression in cancer cells. Materials and Methods: The MTT assay was used to evaluate IC50 values, EB/AO staining to analyze the mode of cell death, and flow cytometry to assess the cell cycle. Quantitative real-time polymerase chain reaction (qRT-PCR) amplification was performed with apoptosis and cell cycle-related gene primers, for cyclin D1, c-myc, survivin, VEGF, Bcl-2, Bax, and caspase-3 to determine alteration of gene expression. Results: Our results showed that n-hexane and chloroform extracts had greatest toxic effects on gastric cancer cells with IC50 values of $6.4{\mu}g/ml$ and $4.6{\mu}g/ml$, respectively, after 72 h. Cell cycle analysis revealed that the population of treated cells in the G1 phase was increased in comparison to controls. Cellular morphological changes indicated induction of apoptosis. In addition, mRNA expression levels of Bax and caspase-3 were increased, and of bcl-2 survivin, VEGF, c-myc and cyclin D1 were decreased. Conclusion: Our study results suggest that D. glabrum has cytotoxic effects on AGS cells, characterized by enhanced apoptosis, reduced cell viability and arrest of cell cycling.

• Korean Journal of Pharmacognosy
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• v.53 no.3
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• pp.153-161
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• 2022

Cotoneaster mongolicus Pojark. (CM), in the family Rosaceae is an endemic plant to the Mongolian region (its name: Moнroл чapraй). In Mongolia, Cotoneaster species as a crude drug is mainly used for inflammatory diseases, diarrhea, and stomach indigestion. In this study, we evaluated the gastro-protective activity underlying mechanism of CM. For in vivo experiments, mice were divided into 5 groups; normal mice (Normal), gastritis mice (Control), gastritis mice treated with sucralfate 10 mg/kg (SC), gastritis mice treated with CM 100 mg/kg (CML), gastritis mice treated with CM 200 mg/kg (CMH). Gastritis was provoked by HCl/ethanol (60% ethanol in 150 mM HCl). After oral administration of each drug, HCl/ethanol was orally administered 90 mins later to induce gastritis. CM alleviated the damage to the gastric mucosa caused. As a result of confirming the expression of protein in gastric tissue through western blot, CM significantly reduced the expression of NF-κB activated due to gastritis. Also, it significantly modulated the Nrf2-Keap1 pathway. These results indicate that CM not only inhibits the nuclear metastasis of NF-𝛋B but also modulates the Nrf2-Keap1 pathway to relieve inflammation of the gastric mucosa.

• Molecules and Cells
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• v.39 no.3
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• pp.217-228
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• 2016

To generate a biobetter that has improved therapeutic activity, we constructed scFv libraries via random mutagenesis of several residues of CDR-H3 and -L3 of hu4D5. The scFv clones were isolated from the phage display libraries by stringent panning, and their antiproliferative activity against HER2-positive cancer cells was evaluated as a primary selection criterion. Consequently, we selected AH06 as a biobetter antibody that had a 7.2-fold increase in anti-proliferative activity ($IC_{50}$: 0.81 nM) against the gastric cancer cell line NCI-N87 and a 7.4-fold increase in binding affinity ($K_D$: 60 pM) to HER2 compared to hu4D5. The binding energy calculation and molecular modeling suggest that the substitution of residues of CDR-H3 to W98, F100c, A101 and L102 could stabilize binding of the antibody to HER2 and there could be direct hydrophobic interactions between the aromatic ring of W98 and the aliphatic group of I613 within HER2 domain IV as well as the heavy and light chain hydrophobic interactions by residues F100c, A101 and L102 of CDR-H3. Therefore, we speculate that two such interactions were exerted by the residues W98 and F100c. A101 and L102 may have a synergistic effect on the increase in the binding affinity to HER2. AH06 specifically binds to domain IV of HER2, and it decreased the phosphorylation level of HER2 and AKT. Above all, it highly increased the overall level of p27 compared to hu4D5 in the gastric cancer cell line NCIN82, suggesting that AH06 could potentially be a more efficient therapeutic agent than hu4D5.

• Korean Journal of Pharmacognosy
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• v.52 no.4
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• pp.257-266
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• 2021

This study evaluated several in vitro activities including the preliminary assessment of the anti-cancer, anti-inflammatory, and anti-diabetic effects of tree sprout extracts. Chlorogenic, caffeic, and p-coumaric acid contents in tree sprouts were analyzed using high-performance liquid chromatography and an ultraviolet detector. Among the studied tree sprout extracts, the ethanol (EtOH) extract of Rhus verniciflua exhibited the most potent anti-cancer effect by suppressing the cell viability of a human gastric adenocarcinoma cell line, with an IC₅₀ of 7.06 ㎍/mL. The EtOH extract of Morus alba (MAB) inhibited the secretion of nitric oxide (NO) at a concentration of 100 ㎍/mL, with an IC₅₀ of 83.44 ㎍/mL. Moreover, the EtOH extract of Securinega suffruticosa inhibited NO secretion with the lowest IC₅₀ of 54.42 ㎍/mL. The EtOH extract of Fraxinus mandschurica was the only extract with effective α-glucosidase inhibitory activity. The total content of chlorogenic, caffeic, and p-coumaric acids was the highest in MAB (14.63 mg/g ext.). In conclusion, the beneficial activities of the tree sprout extracts with high phenolic acid content were generally high. Our results provide a theoretical basis for the development of health-promoting supplements and functional foods.

• KSBB Journal
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• v.26 no.5
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• pp.433-438
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• 2011

These studies were conducted to investigate the alcohol degradation effects of the extract of herbal composition (DTS20) containing Viscum album L., Lycium chinense L., Inonotus obliquus and Acanthopanax senticosus H., on the alcohol administered mice. To investigate anti-hangover effect, alcohol and alcohol dehydrogensae (ADH) concentration of blood were measured after oral administration of ethanol. The administration of DTS20 (200-500 mg/kg) had beneficial actions toward alcohol degradation in acute alcohol treated mice model. The oral administration of DTS20 showed decreased gastric mucous membrane damage produced in ethanol treated mice. In addition, intraperitoneal administration of DTS20 showed anti-inflammatory effects in inhibition tests of vascular permeability produced by acetic acid. DTS20 also reduced the concentration of nitric oxide (NO), tumor necrosis factor (TNF)-${\alpha}$ in macrophages that were activated by LPS. These results demonstrate that DTS20 possesses potential to stimulate the alcohol degradation and inhibit the inflammatory effects in mice.

• Journal of Sasang Constitutional Medicine
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• v.9 no.2
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• pp.227-243
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• 1997

The experimental study used in this paper was done to examine the clinical effects of Taeumchowetang for the gastric ulcer and the function of gastrointestinal tract using rats and mice which were administered orally the water extraction from Taeumchowetang. Then, the counter-action of the water extraction on the isolated ileum and gastric fundus, the inhibitory effects of pylorus-ligated ulcer and indomethacin-induced ulcer, the associations with gastric juice secretion, total acidity, pepsin output, the transportability in the small and large intestine, were studied with administering acetylcholine chloride and barium chloride. In addition, it was investigated whether the central nervous system related to pain control and sleeping time was influenced by Taeumchowetang. The following results have been obtained; 1. As resulting from injection of acetylcholine chloride and barium chloride into the isolated ileum of rats and mice, Taeumchowetang led to have an inhibitory effect on the muscle contraction of the ileum. Then, acetylcholine chloride was measured as lower effect than barium chloride 2. For the inhibitory effect on contraction for the gastric fundus strip in rats by either acetylcholine chloride or barium chloride, the one showed low inhibitory effect, on the other hand the other showed density-dependent effect. 3. The water extraction was given on the pylorus ligated ulcer with using two different administration groups of 1,300mg/kg and 2,600mg/kg, each result was measured as 22.9% and 36.5% for an ulcerous inhibitory effect (p<0.05). 4. According to the two administration groups, the preventive effect was tabulated 18.1% and 29.3% for indomethacin-induced ulcer (p<0.05, P<0.01). 5. For associations with gastric juice secretion, total acidity, pepsin output in the administration group 2,600mg/kg, Taeumchowetang was recognized as having an inhibitory effects related to suppressive actions involving gastric juice secretion(p<0.05), and free acidity(p<0.01), but there was no significant association with total acidity and pepsin output. 6. To know the transportability in the intestine, BaSO4 solution was used. The transportability of the small intestine in the administration group 2,600mg/kg was 22.2% which was statistically significant compared with the large intestine's transportability(P<0.01). 7. In the administration group 1,300mg/kg and 2,600mg/kg, analgesic effect with against acetic acid was measured as being 16.8% and 24.4% which was shown as statistically siginificant(p<0.01). 8. No statistically significant association between Taeumchowetang and sleeping time was found in both 1,300mg/kg and 2,600mg/kg by administering phenobarbital-Na. According to the results of this study, Taeumchowetang has agreed with the effects of literature review. Further more in this study, Taeumchowetang also has preventive effects on pylorus-ligated ulcer. Hence, Teaumchowetang can be significant effect such as both anti ulcer agent and increasing gastric activity for the patients who suffer from gastric ulcer.

• The Korea Journal of Herbology
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• v.34 no.6
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• pp.57-62
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• 2019

Objective : Gastritis is a major complication of gastrointestinal disease. Lonicera japonica is used in folk medicine to treat different diseases such as exopathogenic wind-heat, epidemic febrile diseases, sores, carbuncles and some infectious diseases. Therefore, this study examined the effects of Lonicera japonica water extract (LJE) on HCl/ethano-linduced acute gastric ulceration and anti-oxidants properties. Methods : LC-ESI-IT-TOF MS was employed for rapid identification of major compound from LJE. The antioxidant activities were evaluated through total polyphenol and flavonoid contents and radical scavenging assays and superoxide dismutase (SOD)-like activity. SD rats were randomly divided into five different groups including the normal group, ulcer group, positive group (20 kg/mg of omeprazole, ip), and experimental groups (100 kg/mg and 500 kg/mg of LJE, ip). Results : 4,5-Dicaffeoyl quinic acid, loganic acid, secologanic acid, sweroside, loganin, vogeloside were identified based on the detection of the molecular ion with those of literature data. The LJE was possessed free radical scavenging activities such as DPPH (IC₅₀=189.7 ㎍/㎖), ABTS (IC₅₀=164.5 ㎍/㎖), and SOD-like activity (IC₅₀=405.02 ㎍/㎖). Macroscopic and histological analyses showed LJE treated group were significantly reduced to an extent that it allowed leukocytes penetration of the gastric walls compared with the ulcer group. In addition, an ulcer inhibition rate and prostaglandin E₂ levels were increased in rats treated with LJE. Conclusion : The present study has demonstrated the antioxidantive and gastroprotective effect of LJE, these findings suggested that LJE has the potential for use in treatment of gastric disorders.