[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.1016/j.jgr.2019.11.001

Gastroprotective effects of the nonsaponin fraction of Korean Red Ginseng through cyclooxygenase-1 upregulation

Lee, Jeong-Oog (Department of Aerospace Information Engineering, Bio-Inspired Aerospace Information Laboratory, Konkuk University)
Kim, Ji Hye (Department of Integrative Biotechnology, Sungkyunkwan University)
Kim, Sunggyu (Research and Business Foundation, Sungkyunkwan University)
Kim, Mi-Yeon (School of Systems Biomedical Science, Soongsil University)
Hong, Yo Han (Department of Integrative Biotechnology, Sungkyunkwan University)
Kim, Han Gyung (Department of Integrative Biotechnology, Sungkyunkwan University)
Cho, Jae Youl (Department of Integrative Biotechnology, Sungkyunkwan University)

Publication Information

Journal of Ginseng Research / v.44, no.4, 2020 , pp. 655-663 More about this Journal

Abstract

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.

Keywords

Cyclooxygenase-1 (COX-1); Gastrointestinal protection; Korean Red Ginseng (KRG); Nonsaponin fraction of KRG (NSF);

Citations & Related Records

Times Cited By KSCI : 14 (Citation Analysis)

Reference
Cited By KSCI

1	G Perrone M, Scilimati A, Simone L, Vitale P. Selective COX-1 inhibition: a therapeutic target to be reconsidered. J Current Medicinal Chemistry 2010;17:3769-805. DOI
2	Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J. A comprehensive review of non-steroidal anti-inflammatory drug use in the elderly. Aging and Disease 2018;9:143-50. DOI
3	Drini M. Peptic ulcer disease and non-steroidal anti-inflammatory drugs. Aust Prescr 2017;40:91-3. DOI
4	Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron J, Bombardier C, Cannon C, Farkouh M, FitzGerald G. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Elsevier; 2013.
5	Ryan GB, Majno G. Acute inflammation. A review. Am J Pathol 1977;86:183-276.
6	Fang WF, Broughton A, Jacobson ED. Indomethacin-induced intestinal inflammation. Am J Dig Dis 1977;22:749-60. DOI
7	Neutel CI, Appel WC. The effect of alcohol abuse on the risk of NSAID-related gastrointestinal events. Ann Epidemiol 2000;10:246-50. DOI
8	Koutlas NT, Rusin S, Perjar I, Hollyfield J, Woosley JT, Shaheen NJ, Dellon ES. Impact of smoking, alcohol consumption, and nsaid use on risk for and phenotypes of eosinophilic esophagitis. Gastroenterology 2017;152. S857-S857.
9	Scott PA, Kingsley GH, Scott DL. Non-steroidal anti-inflammatory drugs and cardiac failure: meta-analyses of observational studies and randomised controlled trials. Eur J Heart Fail 2008;10:1102-7. DOI
10	Matsui H, Shimokawa O, Kaneko T, Nagano Y, Rai K, Hyodo I. The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. J Clin Biochem Nutr 2011;48:107-11. DOI
11	Zheng YF, Xie JH, Xu YF, Liang YZ, Mo ZZ, Jiang WW, Chen XY, Liu YH, Yu XD, Huang P, et al. Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats. Chem Biol Interact 2014;222:27-36. DOI
12	Bae EA, Han MJ, Baek NI, Kim DH. In vitro anti-helicobacterpylori activity of panaxytriol isolated from ginseng. JAopr 2001;24:297.
13	Baek KS, Yi YS, Son YJ, Yoo S, Sung NY, Kim Y, Hong S, Aravinthan A, Kim JH, Cho JY. In vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components. J Ginseng Res 2016;40:437-44. DOI
14	Park SH, Choi E, Kim S, Kim DS, Kim JH, Chang S, Choi JS, Park KJ, Roh KB, Lee J, et al. Oxidative stress-protective and anti-melanogenic effects of loliolide and ethanol extract from fresh water green algae, prasiola japonica. Int J Mol Sci 2018;19:2825. DOI
15	Park JG, Kim SC, Kim YH, Yang WS, Kim Y, Hong S, Kim KH, Yoo BC, Kim SH, Kim JH, et al. Anti-inflammatory and antinociceptive activities of anthraquinone- 2-carboxylic acid. Mediators Inflamm 2016;2016:1903849.
16	Baumgartner HK, Starodub OT, Joehl JS, Tackett L, Montrose MH. Cyclooxygenase 1 is required for pH control at the mouse gastric surface. Gut 2004;53:1751-7. DOI
17	Tanaka A, Hatazawa R, Takahira Y, Izumi N, Filaretova L, Takeuchi K. Preconditioning stress prevents cold restraint stress-induced gastric lesions in rats: roles of COX-1, COX-2, and PLA(2). Dig Dis Sci 2007;52:478-87. DOI
18	Liu YH, Zhang ZB, Zheng YF, Chen HM, Yu XT, Chen XY, Zhang X, Xie JH, Su ZQ, Feng XX, et al. Gastroprotective effect of andrographolide sodium bisulfite against indomethacin-induced gastric ulceration in rats. Int Immunopharmacol 2015;26:384-91. DOI
19	Yang Y, Yin B, Lv L, Wang Z, He J, Chen Z, Wen X, Zhang Y, Sun W, Li Y, et al. Gastroprotective effect of aucubin against ethanol-induced gastric mucosal injury in mice. Life Sci 2017;189:44-51. DOI
20	Morsy M, Ashour O, Amin E, Rofaeil R. Gastroprotective effects of telmisartan on experimentally-induced gastric ulcers in rats. Pharmazie 2009;64:590-4.
21	Chassaing B, Aitken JD, Malleshappa M, Vijay-Kumar M. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol 2014;104. Unit 1525.
22	Podolsky DK. Inflammatory bowel disease. New England Journal of Medicine 1991;325:1008-16. DOI
23	Antonisamy P, Kannan P, Aravinthan A, Duraipandiyan V, Arasu MV, Ignacimuthu S, Al-Dhabi NA, Kim JH. Gastroprotective activity of violacein isolated from Chromobacterium violaceum on indomethacin-induced gastric lesions in rats: investigation of potential mechanisms of action. Sci World J 2014;2014:616432.
24	Gretzer B, Maricic N, Respondek M, Schuligoi R, Peskar BM. Effects of specific inhibition of cyclo-oxygenase-1 and cyclo-oxygenase-2 in the rat stomach with normal mucosa and after acid challenge. Br J Pharmacol 2001;132:1565-73. DOI
25	Wallace JL. Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself? Physiol Rev 2008;88:1547-65. DOI
26	Medzhitov R, Janeway Jr CA. Decoding the patterns of self and nonself by the innate immune system. Science 2002;296:298-300. DOI
27	Karre K, Ljunggren HG, Piontek G, Kiessling RJN. Selective rejection of He2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 1986;319:675. DOI
28	de Mattos BR, Garcia MP, Nogueira JB, Paiatto LN, Albuquerque CG, Souza CL, Fernandes LG, Tamashiro WM, Simioni PU. Inflammatory bowel disease: an overview of immune mechanisms and biological treatments. Mediators Inflamm 2015;2015:493012. DOI
29	Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003;423:356-61. DOI
30	Qomaladewi NP, Kim MY, Cho JY. Autophagy and its regulation by ginseng components. J Ginseng Res 2019;43:349-53. DOI
31	Kim E, Yi YS, Son YJ, Han SY, Kim DH, Nam G, Hossain MA, Kim JH, Park J, Cho JY. BIOGF1K, a compound K-rich fraction of ginseng, plays an antiinflammatory role by targeting an activator protein-1 signaling pathway in RAW264.7 macrophage-like cells. J Ginseng Res 2018;42:233-7. DOI
32	Lee DH, Cho HJ, Kang HY, Rhee MH, Park HJ. Total saponin from Korean red ginseng inhibits thromboxane A2 production associated microsomal enzyme activity in platelets. J. Ginseng Research 2012;36:40. DOI
33	Ahn H, Han BC, Kim J, Kang SG, Kim PH, Jang KH, So SH, Lee SH, Lee GS. Nonsaponin fraction of Korean Red Ginseng attenuates cytokine production via inhibition of TLR4 expression. J Ginseng Res 2019;43:291-9. DOI
34	Okuda H. Biological activities non-saponin fractions in Korean red ginseng. In: Proc.'99 KoreaneJapan ginseng symposium. Korea: The Korean Society of Ginseng Seoul; 1999. p. 59-69.
35	Park K-Y, Kwon DY, Lee KW, Park S. Korean functional foods: composition, processing and health benefits. CRC Press; 2018.
36	Nag SA, Qin J, Wang W, Wang M-H, Wang H, Zhang R. Ginsenosides as anticancer agents: in vitro and in vivo activities, structure-activity relationships, and molecular mechanisms of action. Front Pharmacol 2012;3:25. DOI
37	Han SY, Kim J, Kim E, Kim SH, Seo DB, Kim JH, Shin SS, Cho JY. AKT-targeted anti-inflammatory activity of Panax ginseng calyx ethanolic extract. J Ginseng Res 2018;42:496-503. DOI
38	Lee JO, Choi E, Shin KK, Hong YH, Kim HG, Jeong D, Hossain MA, Kim HS, Yi YS, Kim D, et al. Compound K, a ginsenoside metabolite, plays an antiinflammatory role in macrophages by targeting the AKT1-mediated signaling pathway. J Ginseng Res 2019;43:154-60. DOI
39	Kulmacz RJ, Lands WE. Stoichiometry and kinetics of the interaction of prostaglandin H synthase with anti-inflammatory agents. J Biol Chem 1985;260:12572-8. DOI
40	Oh HA, Kim DE, Choi HJ, Kim NJ, Kim DH. Anti-fatigue effects of 20 (S)-protopanaxadiol and 20 (S)-protopanaxatriol in mice. Biol Pharm Bull 2015;38:1415-9. DOI
41	Han B, Park M, Woo L, Woo W, Han Y. Antioxidant components of Korean ginseng. Korean Biochem J 1979;12:33.
42	Ahn SI, Kim SK, Yang BW, Lee ES, Kang CS, Hahm YT. Analysis of ginsenosides and non-saponin components of red ginseng from landraces and new varieties. Kor J Hortic Sci Technol 2016;34:790-8.
43	Kang S, Min H. Ginseng, the 'immunity boost': the effects of panax ginseng on immune system. J Ginseng Res 2012;36:354-68. DOI
44	Byeon SE, Lee J, Kim JH, Yang WS, Kwak Y-S, Kim SY, Choung ES, Rhee MH, Cho JY. Molecular mechanism of macrophage activation by red ginseng acidic polysaccharide from Korean red ginseng. JMoi 2012:2012.
45	Baek KS, Hong YD, Kim Y, Sung NY, Yang S, Lee KM, Park JY, Park JS, Rho HS, Shin SS, et al. Anti-inflammatory activity of AP-SF, a ginsenoside-enriched fraction, from Korean ginseng. J Ginseng Res 2015;39:155-61. DOI
46	Hwang HS, Han KJ, Ryu YH, Yang EJ, Kim YS, Jeong SY, Lee YS, Lee MS, Koo ST, Choi SM. Protective effects of electroacupuncture on acetylsalicylic acidinduced acute gastritis in rats. World J Gastroenterol 2009;15:973-7. DOI
47	Pulli B, Ali M, Forghani R, Schob S, Hsieh KL, Wojtkiewicz G, Linnoila JJ, Chen JW. Measuring myeloperoxidase activity in biological samples. PLoS One 2013;8:e67976. DOI
48	Yang WS, Lee J, Kim TW, Kim JH, Lee S, Rhee MH, Hong S, Cho JY. Src/ $NF-{\kappa}B$ -targeted inhibition of LPS-induced macrophage activation and dextran 662 J Ginseng Res 2020;44:655-663 sodium sulphate-induced colitis by Archidendron clypearia methanol extract. Journal of Ethnopharmacology 2012;142:287-93. DOI
49	Suleyman H, Demircan B, Karagoz Y. Anti-inflammatory and side effects of cyclo-oxygenase inhibitors. Pharmacological Reports 2007;59:247.
50	Jackson LM, Wu KC, Mahida YR, Jenkins D, Hawkey CJ. Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated human gastric mucosa. Gut 2000;47:762-70. DOI
51	Lucas S. The pharmacology of indomethacin. Headache 2016;56:436-46. DOI
52	Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res 2003;110:255-8. DOI
53	Malfertheiner P, Chan FK, McColl KE. Peptic ulcer disease. Lancet 2009;374:1449-61. DOI
54	Kurata JH. Ulcer epidemiology: an overview and proposed research framework. Gastroenterology 1989;96:569-80. DOI

24	(2020) Molecules The Anti-Cancer Effect of Linusorb B3 from Flaxseed Oil through the Promotion of Apoptosis, Inhibition of Actin Polymerization, and Suppression of Src Activity in Glioblastoma Cells / 25 (24) , 5881
6	(2020) The American journal of Chinese medicine <I>Matricaria chamomilla</I> (Chamomile) Ameliorates Muscle Atrophy in Mice by Targeting Protein Catalytic Pathways, Myogenesis, and Mitochondrial Dysfunction / 49 (6) , 1493
	(2021) Evidence-based Complementary and Alternative Medicine : eCAM Antioxidative and Skin Protective Effects of Canarium subulatum Methanol Extract on Keratinocytes / 2021 , 1
6	(2021) Molecules Olea europaea Suppresses Inflammation by Targeting TAK1-Mediated MAP Kinase Activation / 26 (6) , 1540
9	(2020) Molecules Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway / 26 (9) , 2529
10	(2020) Molecules TAK1/AP-1-Targeted Anti-Inflammatory Effects of Barringtonia augusta Methanol Extract / 26 (10) , 3053
16	(2020) International journal of molecular sciences Kahweol Exerts Skin Moisturizing Activities by Upregulating STAT1 Activity / 22 (16) , 8864
17	(2021) Molecules Protective Effect of Potentilla glabra in UVB-Induced Photoaging Process / 26 (17) , 5408
19	(2021) Molecules Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1 / 26 (19) , 6073
20	(2020) Molecules Anti-Gastritis and Anti-Lung Injury Effects of Pine Tree Ethanol Extract Targeting Both NF-κB and AP-1 Pathways / 26 (20) , 6275
21	(2020) Molecules Caragana rosea Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways / 26 (21) , 6660
11	(2020) Plants Anti-Inflammatory Effects of Huberia peruviana Cogn. Methanol Extract by Inhibiting Src Activity in the NF-κB Pathway / 10 (11) , 2335