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Gastroprotective effect of araloside A on ethanol- and aspirin-induced gastric ulcer in mice: involvement of H+/K+-ATPase and mitochondrial-mediated signaling pathway

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Abstract

The aim of this study was to elucidate the gastroprotective activity and possible mechanism of involvement of araloside A (ARA) against ethanol- and aspirin-induced gastric ulcer in mice. The experimental mice were randomly divided into control, model, omeprazole (20 mg/kg, orally) and ARA (10, 20 and 40 mg/kg, orally). Gastric ulcer in mice was induced by intragastric administration of 80% ethanol (10 mL/kg) containing 15 mg/mL aspirin 4 h after drug administration on day 7. The results indicated that ARA could significantly raise gastric juice volume and acidity; ameliorate gastric mucosal blood flow, gastric binding mucus volume, ulcer index and ulcer inhibition rate; suppress H+/K+-ATPase activity, which was confirmed by computer-aided docking simulations; inhibit the release of mitochondrial cytochrome c into the cytoplasm; inhibit caspase-9 and caspase-3 activities and down-regulate mRNA expression levels; down-regulate the mRNA and protein expressions of apoptosis protease-activating factor-1 and protein expression of cleaved poly(ADP ribose) polymerase-1; and up-regulate Bcl-2 mRNA and protein expressions and down-regulate Bax mRNA and protein expressions, thus elevating the Bcl-2/Bax ratio in a dose-dependent manner. Histopathological observations further provided supportive evidence for the aforementioned results. The results demonstrated that ARA exerted beneficial gastroprotective effects on alcohol- and aspirin-induced gastric ulcer in mice, which was related to suppressing H+/K+-ATPase activity as well as pro-apoptotic protein expression, and promoting anti-apoptotic protein expression, thus alleviating gastric mucosal injury and cell death.

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References

  1. Zhang QY, Huang NY, Wang JZ, Luo HJ, He HB, Ding MR, Deng WQ, Zou K (2013) The H+/K+-ATPase inhibitory activities of Trametenolic acid B from Trametes lactinea (Berk.) Pat, and its effects on gastric cancer cells. Fitoterapia 89:210–217

    Article  CAS  PubMed  Google Scholar 

  2. Shin JM, Vagin O, Munson K, Kidd M, Modlin IM, Sachs G (2008) Molecular mechanisms in therapy of acid-related diseases. Cell Mol Life Sci 65:264–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shin JM, Munson K, Vagin O, Sachs G (2009) The gastric H+/K+-ATPase: structure, function, and inhibition. Pflugers Arch 457:609–622

    Article  CAS  PubMed  Google Scholar 

  4. Weidemüller C, Hauser K (2009) Ion transport and energy transduction of P-type ATPases: implications from electrostatic calculations. Biochim Biophys Acta 1787:721–729

    Article  CAS  PubMed  Google Scholar 

  5. Chakraborty S, Stalin S, Das N, Choudhury ST, Ghosh S, Swarnakar S (2012) The use of nano-quercetin to arrest mitochondrial damage and MMP-9 upregulation during prevention of gastric inflammation induced by ethanol in rat. Biomaterials 33:2991–3001

    Article  CAS  PubMed  Google Scholar 

  6. Lee GJ, Chae SJ, Jeong JH, Lee SR, Ha SJ, Pak YK, Kim W, Park HK (2011) Characterization of mitochondria isolated from normal and ischemic hearts in rats utilizing atomic force microscopy. Micron 42:299–304

    Article  CAS  PubMed  Google Scholar 

  7. Lee MJ, Chen HM, Tzang BS, Lin CW, Wang CJ, Liu JY, Kao SH (2011) Ocimum gratissimum aqueous extract protects H9c2 myocardiac cells from H(2)O(2)-induced cell apoptosis through Akt signalling. Evid Based Complement Alternat Med. https://doi.org/10.1155/2011/578060

    Article  PubMed  PubMed Central  Google Scholar 

  8. Orsucci D, Mancuso M, Siciliano G (2008) Mitochondria, oxidative stress and PARP-1 network: a new target for neuroprotective effects of tetracyclines? J Physiol 586:2427–2428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tjandrawinata RR, Nailufar F, Arifin PF (2013) Hydrogen potassium adenosine triphosphatase activity inhibition and downregulation of its expression by bioactive fraction DLBS2411 from Cinnamomum burmannii in gastric parietal cells. Int J Gen Med 6:807–815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yang ZF, Tang HF, Jia YY, Xi MM, Wen AD (2008) The effect of total saponin of Aralia Taibaiensison Glycemia Lipidan antioxidation in hyperglyce mice. Pharm J Chin PLA 24:110–113

    CAS  Google Scholar 

  11. Yook CS (1981) Medicinal plants of Korea. Jinmyung Publishing Co., Ltd, Seoul

    Google Scholar 

  12. Namba T (1980) The encyclopedia of Wakan-Yaku with color pictures, vol Vol II. Hoikusha Publishing Co., Ltd, Osaka

    Google Scholar 

  13. Munwha Broadcast Corporation (ed.) (1987) Korean folk medicinal therapeutics. Keumbak Publishing. Co., Ltd, Seoul

  14. Lee EB, Kim OJ, Kang SS, Jeong C (2005) Araloside A, an antiulcer constituent from the root bark of Aralia elata. Biol Pharm Bull 28:523–526

    Article  CAS  PubMed  Google Scholar 

  15. He HB, Zhang YF, Li XM, Li XQ, Qin HL, Liu CX, Tang HB, Wang JZ, Zou K (2017) Effect of triterpene from Chaenomeles speciose (Sweet) Nakai on gastric acid secretion and gastric mucosal barrier function in indomethacin induced mice. Biotic Resour 39:211–216

    Google Scholar 

  16. Martín MJ, Marhuenda E, Pérez-Guerrero C, Franco JM (1994) Antiulcer effect of naringin on gastric lesions induced by ethanol in rats. Pharmacology 49:144–150

    Article  PubMed  Google Scholar 

  17. Shinoda T, Ogawa H, Cornelius F, Toyoshima C (2009) Crystal structure of the sodium-potassium pump at 2.4 A resolution. Nature 459:446–450

    Article  CAS  PubMed  Google Scholar 

  18. Berman HM, Westbrook J, Feng Z (2000) The protein data bank. Anhui Med Pharma J 28:235–242

    CAS  Google Scholar 

  19. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234:779–815

    Article  CAS  PubMed  Google Scholar 

  21. Schrödinger LLC (2010) www.schrodinger.com (New York). Accessed 30 Dec 2017

  22. Vaguine AA, Richelle J, Wodak SJ (1999) SFCHECK: a unified set of procedures for evaluating the quality of macromolecular structure-factor data and their agreement with the atomic model. Acta Crystallogr D Biol Crystallogr 55:191–205

    Article  CAS  PubMed  Google Scholar 

  23. DeLano WL (2004) The PyMOL molecular graphics system. DeLano Scientific, San Carlos

    Google Scholar 

  24. Wang S, He HB, Xiao SZ, Wang JZ, Bai CH, Wei N, Zou K (2014) Comparison of cardioprotective effects of labeled and unlabeled oleanoic acids with new BOPIM dye on primary neonatal rat cardiomyocytes following hypoxia/reoxygenation injury. Pharmacol Rep 66:677–685

    Article  CAS  PubMed  Google Scholar 

  25. Sohn YA, Hwang SA, Lee SY, Hwang IY, Kim SW, Kim SY, Moon A, Lee YS, Kim YH, Kang KJ, Jeong CS (2015) Protective effect of liriodendrin isolated from Kalopanax pictus against gastric injury. Biomol Ther (Seoul) 23:53–59

    Article  CAS  Google Scholar 

  26. Bhattacharya S, Banerjee D, Bauri AK, Chattopadhyay S, Bandyopadhyay SK (2007) Healing property of the Piper betel phenol, allylpyrocatechol against indomethacin-induced stomach ulceration and mechanism of action. World J Gastroenterol 13:3705–3713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lv RX, Du LL, Lu CW, Wu JH, Ding MC, Wang C, Mao NF, Shi ZC (2017) Allicin protects against H2O2- induced apoptosis of PC12 cells via the mitochondrial pathway. Exp Ther Med 14:2053–2059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Huang SL, He HB, Zou K, Bai CH, Xue YH, Wang JZ, Chen JF (2014) Protective effect of tomatine against hydrogen peroxide-induced neurotoxicity in neuroblastoma (SH-SY5Y) cells. J Pharm Pharmacol 66:844–854

    Article  CAS  PubMed  Google Scholar 

  29. Zhao HG, Zhou SL, Lin YY, Dai HF, Huang FY (2017) Toxicarioside N induces apoptosis in human gastric cancer SGC-7901 cell by activating the p38MAPK pathway. Arch Pharm Res. https://doi.org/10.1007/s12272-017-0956-4

    Article  PubMed  Google Scholar 

  30. Namulema J, Nansunga M, Kato CD, Kalange M, Olaleye SB (2018) Thyroid hormones increase stomach goblet cell numbers and mucin expression during indomethacin induced ulcer healing in Wistar rats. Thyroid Res 11:1–8

    Article  CAS  Google Scholar 

  31. Lamers CB, Biemond I, Masclee AA, Veenendaal RA (1996) Therapy and prevention of gastric ulcer. Yale J Biol Med 69:265–270

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Higuchi K, Watanabe T, Tanigawa T, Tominaga K, Fujiwara Y, Arakawa T (2010) Sofalcone, a gastroprotective drug, promotes gastric ulcer healing following eradication therapy for Helicobacter pylori: a randomized controlled comparative trial with cimetidine, an H2-receptor antagonist. J Gastroenterol Hepatol Suppl 1:S155–S160

    Article  CAS  Google Scholar 

  33. Walker J, Hell J, Liszt KI, Dresel M, Pignitter M, Hofmann T, Somoza V (2012) Identification of beer bitter acids regulating mechanisms of gastric acid secretion. J Agric Food Chem 60:1405–1412

    Article  CAS  PubMed  Google Scholar 

  34. Lewin MJ (1999) Cellular mechanisms and inhibitors of gastric acid secretion. Drugs Today (Barc) 35:743–752

    Article  CAS  Google Scholar 

  35. Bienia A, Sodolski W, Luchowska E (2002) The effect of chronic alcohol abuse on gastric and duodenal mucosa. Ann Univ Mariae Curie Sklodowska Med 57:570–582

    PubMed  Google Scholar 

  36. O’Connor HJ, Dixon MF, Wyatt JI, Axon AT, Dewar EP, Johnston D (1987) Campylobacter pylori and peptic ulcer disease. Lancet 2:633–634

    Article  PubMed  Google Scholar 

  37. Tsai HF, Hsu PN (2017) Modulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by Helicobacter pylori in immune pathogenesis of gastric mucosal damage. J Microbiol Immunol Infect 50:4–9

    Article  CAS  PubMed  Google Scholar 

  38. Luo X, Kraus WL (2012) On PAR with PARP: cellular stress signaling through poly (ADP-ribose) and PARP-1. Genes Dev 26:417–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Krishnakumar R, Kraus WL (2010) The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol Cell 39:8–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cregan SP, Dawson VL, Slack RS (2004) Role of AIF in caspase-dependent and caspase- independent cell death. Oncogene 23:2785–2796

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (No: 81202905, 31370373).

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Authors and Affiliations

  1. Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, 8 University Avenue, Yichang, 443002, China

    Haibo He, Xiaomei Li, Haili Yu, Yumin He, Xiaoqin Li, Junzhi Wang, Huajun Luo & Kun Zou

  2. Division of Pharmacognosy, Department of Medicinal Resources, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Shu Zhu & Katsuko Komatsu

  3. Shaanxi Key Laboratory of Traditional Chinese Medicine Foundation and New Drug Research, Shaanxi University of Chinese Medicine, Shiji Road, Xianyang, 712046, China

    Dongyan Guo

  4. Seventh People’s Hospital of Wenzhou, 552 Shanxi East Road, Wenzhou, 325005, China

    Daoxiang Xu

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  1. Haibo He
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Correspondence to Dongyan Guo or Junzhi Wang.

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He, H., Li, X., Yu, H. et al. Gastroprotective effect of araloside A on ethanol- and aspirin-induced gastric ulcer in mice: involvement of H+/K+-ATPase and mitochondrial-mediated signaling pathway. J Nat Med 73, 339–352 (2019). https://doi.org/10.1007/s11418-018-1256-0

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  • DOI: https://doi.org/10.1007/s11418-018-1256-0

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