Browse > Article
http://dx.doi.org/10.1016/j.jgr.2018.04.001

Evaluation of the gastroprotective effects of 20 (S)-ginsenoside Rg3 on gastric ulcer models in mice  

Zhang, Kai (Research Center of Natural Drug, School of Pharmaceutical Sciences, Jilin University)
Liu, Ying (Department of General Surgery, The Second Hospital of Jilin University)
Wang, Cuizhu (Research Center of Natural Drug, School of Pharmaceutical Sciences, Jilin University)
Li, Jiannan (Department of General Surgery, The Second Hospital of Jilin University)
Xiong, Lingxin (Research Center of Natural Drug, School of Pharmaceutical Sciences, Jilin University)
Wang, Zhenzhou (Research Center of Natural Drug, School of Pharmaceutical Sciences, Jilin University)
Liu, Jinping (Research Center of Natural Drug, School of Pharmaceutical Sciences, Jilin University)
Li, Pingya (Research Center of Natural Drug, School of Pharmaceutical Sciences, Jilin University)
Publication Information
Journal of Ginseng Research / v.43, no.4, 2019 , pp. 550-561 More about this Journal
Abstract
Background: Gastric ulcer (GU) is a common gastrointestinal disease that can be induced by many factors. Finding an effective treatment method that contains fewer side effects is important. 20 (S)-ginsenoside Rg3 is a kind of protopanaxadiol and has shown superior antiinflammatory and antioxidant effects in many studies, especially cancer studies. In this study, we examined the treatment efficacy of 20 (S)-ginsenoside Rg3 on GU. Methods: Three kinds of GU models, including an alcohol GU model, a pylorus-ligated GU model, and an acetic acid GU model, were used. Mouse endothelin-1 (ET-1) and nitric oxide (NO) levels in blood and epidermal growth factor (EGF), superoxide dismutase, and NO levels in gastric mucosa were evaluated. Hematoxylin and eosin staining of gastric mucosa and immunohistochemical staining of ET-1, inducible nitric oxide synthase (NOS2), and epidermal growth factor receptors were studied. Ulcer index (UI) scores and UI ratios were also analyzed to demonstrate the GU conditions in different groups. Furthermore, Glide XP from $Schr{\ddot{o}}dinger$ was used for molecular docking to clarify the interactions between 20 (S)-ginsenoside Rg3 and EGF and NOS2. Results: 20 (S)-ginsenoside Rg3 significantly decreased the UI scores and UI ratios in all the three GU models, and it demonstrated antiulcer effects by decreasing the ET-1 and NOS2 levels and increasing the NO, superoxide dismutase, EGF, and epidermal growth factor receptor levels. In addition, high-dose 20 (S)-ginsenoside Rg3 showed satisfactory gastric mucosa protection effects. Conclusion: 20 (S)-ginsenoside Rg3 can inhibit the formation of GU and may be a potential therapeutic agent for GU.
Keywords
Antiinflammation; Antioxidant; 20 (S)-ginsenoside Rg3; Gastric ulcer; Ulcer index;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Ishikawa T, Seto M, Banno H, Kawakita Y, Oorui M, Taniguchi T, Ohta Y, Tamura T, Nakayama A, Miki H, et al. Design and synthesis of novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors bearing a Pyrrolo 3,2-d pyrimidine Scaffold. J Med Chem 2011;54(23):8030-50.   DOI
2 Zhang N-Q, Wang C-Z, Wang Z-Z, Li Z, Sai J-Y, Meng Y, Wang F, Li P-Y, Liu J-P. Anti-myocardial ischaemic effect of pseudoginsenoside F11 by inhibiting expression of beta1-adrenoceptor in rats with coronary artery ligation. J Funct Foods 2017;36:224-32.   DOI
3 Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, Repasky MP, Knoll EH, Shelley M, Perry JK, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 2004;47(7):1739-49.   DOI
4 Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, Sanschagrin PC, Mainz DT. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 2006;49(21):6177-96.   DOI
5 Halgren TA, Murphy RB, Friesner RA, Beard HS, Frye LL, Pollard WT, Banks JL. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem 2004;47(7):1750-9.   DOI
6 Xiong L, Qi Z, Zheng B, Li Z, Wang F, Liu J, Li P. Inhibitory effect of triterpenoids from panax ginseng on coagulation factor X. Molecules (Basel, Switzerland) 2017;22(4).
7 Garcin ED, Arvai AS, Rosenfeld RJ, Kroeger MD, Crane BR, Andersson G, Andrews G, Hamley PJ, Mallinder PR, Nicholls DJ, et al. Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase. Nat Chem Biol 2008;4(11):700-7.   DOI
8 Chang X, Luo F, Jiang W, Zhu L, Gao J, He H, Wei T, Gong S, Yan T. Protective activity of salidroside against ethanol-induced gastric ulcer via the MAPK/NFkappa B pathway in vivo and in vitro. Int Immunopharmacol 2015;28(1):604-15.   DOI
9 Li S-L, Zhao J-R, Ren X-Y, Xie J-P, Ma Q-Z, Rong Q-H. Increased expression of matrix metalloproteinase-9 associated with gastric ulcer recurrence. World J Gastroenterol 2013;19(28):4590-5.   DOI
10 Sakatoku Y, Fukaya M, Fujieda H, Kamei Y, Hirata A, Itatsu K, Nagino M. Tracheoesophageal fistula after total resection of gastric conduit for gastroaortic fistula due to gastric ulcer. Surg Case Rep 2017;3.
11 Li X, Wang L, Li G, Zheng X, Duan C. Expression of miR-204 and MMP-9 in Helicobacter pylori-associated gastric ulcer. Int J Clin Exp Med 2016;9(5):7928-36.
12 Biswas K, Bandyopadhyay U, Chattopadhyay I, Varadaraj A, Ali E, Banerjee RK. A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical. J Biolog Chem 2003;278(13):10993-1001.   DOI
13 Al Batran R, Al-Bayaty F, Al-Obaidi MMJ, Abdualkader AM, Hadi HA, Ali HM, Abdulla MA. In vivo antioxidant and antiulcer activity of Parkia speciosa ethanolic leaf extract against ethanol-induced gastric ulcer in rats. Plos One 2013;8(5).
14 Cheng L, Sun X, Hu C, Jin R, Sun B, Shi Y, Cui W, Zhang Y. In vivo early intervention and the therapeutic effects of 20(S)-ginsenoside Rg3 on hypertrophic scar formation. Plos One 2014;9(12).
15 Lee I-S, Uh I, Kim K-S, Kim K-H, Park J, Kim Y, Jung J-H, Jung H-J, Jang H-J. Antiinflammatory effects of ginsenoside Rg3 via NF-kappaB pathway in A549 cells and human asthmatic lung tissue. J Immunol Res 2016;2016. 7521601-7521601.
16 Nishida T, Tsuji S, Kimura A, Tsujii M, Ishii S, Yoshio T, Shinzaki S, Egawa S, Irie T, Yasumaru M, et al. Endothelin-1, an ulcer inducer, promotes gastric ulcer healing via mobilizing gastric myofibroblasts and stimulates production of stroma-derived factors. Am J Physiol Gastrointest Liver Physiol 2006;290(5):G1041-50.   DOI
17 Kang H, Hwang Y-G, Lee T-G, Jin C-R, Cho CH, Jeong H-Y, Kim D-O. Use of gold nanoparticle fertilizer enhances the ginsenoside contents and anti-inflammatory effects of red ginseng. J Microbiol Biotechnol 2016;26(10):1668-74.   DOI
18 Park JY, Choi P, Kim T, Ko H, Kim H-K, Kang KS, Ham J. Protective effects of processed ginseng and its active ginsenosides on cisplatin-induced nephrotoxicity: in vitro and in vivo studies. JAgric Food Chem 2015;63(25):5964-9.   DOI
19 Du Y, Zhao W, Lu L, Zheng J, Hu X, Yu Z, Zhu L. Study on the antiulcer effects of Veronicastrum axillare on gastric ulcer in rats induced by ethanol based on tumor necrosis factor-alpha (TNF-alpha) and endothelin-1 (ET-1). Asian Pacific J Trop Biomed 2013;3(12):925-30.   DOI
20 Iaquinto G, Giardullo N, Taccone W, Leandro G, Pasquale L, De Luca L, Szabo S. Role of endogenous endothelin-1 in ethanol-induced gastric mucosal damage in humans. Dig Dis Sci 2003;48(4):663-9.   DOI
21 Kim D-K, Kweon K-J, Kim P, Kim H-J, Kim S-S, Sohn N-W, Maeng S, Shin J-W. Ginsenoside Rg3 improves recovery from spinal cord injury in rats via suppression of neuronal apoptosis. Pro-inflamm Mediat Microglial Activ Mol 2017;22(1).
22 Shen Y, Sun J, Niu C, Yu D, Chen Z, Cong W, Geng F. Mechanistic evaluation of gastroprotective effects of Kangfuxin on ethanol-induced gastric ulcer in mice. Chemico-biolog Interact 2017;273:115-24.   DOI
23 Marotta F, Tajiri H, Safran P, Fesce E, Ideo G. Ethanol-related gastric mucosal damage: evidence of a free radical-mediated mechanism and beneficial effect of oral supplementation with bionormalizer, a novel natural antioxidant. Digestion 1999;60(6):538-43.   DOI
24 Goswami SK, Rand AA, Wan D, Yang J, Inceoglu B, Thomas M, Morisseau C, Yang G-Y, Hammock BD. Ethanol-related gastric mucosal damage: evidence of a free radical-mediated mechanism and beneficial effect of oral supplementation with bionormalizer, a novel natural antioxidant. Digestion 1999;60(6):538-43.   DOI
25 Kangwan N, Park J-M, Kim E-H, Hahm KB. Quality of healing of gastric ulcers: natural products beyond acid suppression. World J Gastrointest Pathophysiol 2014;5(1):40-7.   DOI
26 Lee CH, Kim J-H. A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J Ginseng Res 2014;38(3):161-6.   DOI
27 Chen QS. Pharmacological studies on notoginseng saponins isolated from the fibrous root of Panax notoginseng. Zhong Yao Tong Bao (Beijing, China : 1981) 1987;12(3):45-7.
28 Lee MR, Yun BS, Sung CK. Comparative study of white and steamed black Panax ginseng, P. quinquefolium, and P. Notoginseng on cholinesterase inhibitory and antioxidative activity. J Ginseng Res 2012;36(1):93-101.   DOI
29 Zhang L-P, Jiang Y-C, Yu X-F, Xu H-I, Li M, Zhao X-Z, Sui D-Y. Ginsenoside Rg3 improves cardiac function after myocardial ischemia/reperfusion via attenuating apoptosis and inflammation. Evid Based Complement Altern Med 2016.
30 He B, Chen P, Yang J, Yun Y, Zhang X, Yang R, Shen Z. Neuroprotective effect of 20(R)-ginsenoside Rg(3) against transient focal cerebral ischemia in rats. Neurosci Lett 2012;526(2):106-11.   DOI
31 Li G, Zhang X-X, Lin L, Liu X-N, Ma C-J, Li J, Wang C-B. Preparation of ginsenoside Rg3 and protection against $H_{2}O_{2}$-Induced oxidative stress in human neuroblastoma SK-N-SH cells. J Chem 2014.
32 Xia G-Y, Yao T, Zhang B-Y, Li Y, Kang N, Cao S-J, Ding L-Q, Chen L-X, Qiu F. Withapubesides A-D: natural inducible nitric oxide synthase (iNOS) inhibitors from Physalis pubescens. Organic Biomol Chem 2017;15(47):10016-23.   DOI
33 Singh S, Khajuria A, Taneja SC, Khajuria RK, Singh J, Johri RK, Qazi GN. The gastric ulcer protective effect of boswellic acids, a leukotriene inhibitor from Boswellia serrata, in rats. Phytomedicine 2008;15(6-7):408-15.   DOI