Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Inhibitory Effects of Chios Mastic Gum on Gastric Acid Secretion by Histamine-Related Pathway in a Rat Model and Primary Parietal Cells

위염 동물모델과 위 벽세포에서 히스타민 경로를 통한 매스틱검(Chios Mastic Gum)의 위산 분비 억제효과 및 기전 연구

  • Received : 2014.08.12
  • Accepted : 2014.08.14
  • Published : 2014.10.31
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Abstract

The object of this study was to investigate the inhibitory effects of chios mastic gum (MG) on gastric acid secretion in an ethanol-induced SD rat model and primary parietal cells. Rats were randomly divided into four groups: Vehicle (normal group), Control (treated with ethanol), MG50 (treated with ethanol and mastic gum at 50 mg/kg b.w), MG100 (treated with ethanol and mastic gum at 100 mg/kg b.w). Groups treated with both MG50 and MG100 showed attenuation of gastric mucosal injury, sub-epithelial loss, hemorrhaging, and gastric juice secretion. We also examined the acidity of gastric juice during gastric injury. Oral administration of both MG50 and MG100 significantly decreased acidity of gastric juice by % and %, respectively. To examine the stimulatory factors related to gastric acid secretion, mRNA expression levels of H2r, M3r, CCK2r, and $H^+/K^+$ ATPase were measured by real-time PCR. Compared with a vehicle group, mRNA expression levels of H2r, CCK2r, and $H^+/K^+$ ATPase clearly increased in the control group. However, levels of H2r, CCK2r, and $H^+/K^+$ ATPase slightly but significantly decreased in MG-treated groups compared with control. Blood level of histamine significantly decreased in MG-treated groups, which indicates the involvement of MG on in histamine-related acid secretion. To identify the mode of action of MG in regulating histamine-related pathways, intracellular level of cAMP and mRNA levels of H2r, M3r, CCK2r, and $H^+/K^+$ ATPase were measured in primary parietal cells. While mRNA levels of M3r and CCK2r remained unchanged, levels of H2r and $H^+/K^+$ ATPase significantly decreased upon MG treatment. Subsequently, intracellular levels of cAMP decreased. These results suggest that mastic gum has the ability to inhibit gastric acid secretion by regulating a histamine-related pathway.

본 연구는 위 벽세포 in vitro 실험모델과 알코올로 위를 자극한 in vivo 실험모델을 이용하여 매스틱 검의 위산 분비 억제 및 위장 점막 보호 효과를 확인하고자 하였다. 위 조직의 병리학적인 관찰을 통하여 효과를 관찰한 결과 알코올로 위를 자극한 군에서 위 점막 조직의 손상과 표면 상피세포의 손실을 관찰할 수 있었으나, 매스틱 검 50 및 100 mg/kg 투여한 군에서 모두 control 그룹과 비교했을 때 손상이 회복되었음을 확인할 수 있었다. 위액 분비량 및 위액 산도를 비교한 결과에서도 알코올의 자극으로 인하여 증가한 위액 분비량과 위액 산도를 매스틱 검이 유의적으로 감소시켰음을 확인할 수 있었다. 혈장 histamine 농도와 그로 인해 영향을 받은 H2r 발현량 변화로 위산 분비 관련 인자를 확인한 결과에서도 매스틱 검을 투여한 그룹에서 유의적으로 그 농도가 감소한 것을 확인하였다. 또한 위 벽세포에서 위산 분비 증가와 관련된 수용체인 CCK2r과 $H^+/K^+$ APTase 발현 변화도 역시 매스틱 검의 투여가 효과적으로 발현을 억제한 것으로 나타났다. 이러한 동물실험 결과를 바탕으로 세포 수준에서의 기전 규명을 위한 연구를 추가적으로 진행하였으며, 세포 내 cAMP 농도, $H^+/K^+$ APTase 및 H2r의 발현 변화를 관찰한 결과 매스틱 검의 처리가 효과적으로 이들의 발현을 감소시켰음을 확인하였다. 따라서 매스틱 검의 위산 분비 억제 및 점막 보호 활성 효과는 형태학적 및 병리학적 관찰, histamine 분비 억제, 수용체 발현 억제효과 등으로 확인한 결과, histamine을 통한 위산 분비 경로를 조절함으로써 위산 분비 및 위장 점막 손상에 대해 보호 효과를 나타내었으며 이는 이전 실험 결과들과 동일한 농도에서 효과가 나타났음을 확인하였다.

Keywords

References

  1. Kay HH, Grindle KM, Magness RR. 2000. Ethanol exposure induces oxidative stress and impairs nitric oxide availability in the human placental villi: a possible mechanism of toxicity. Am J Obstet Gynecol 182: 682-688. https://doi.org/10.1067/mob.2000.104201
  2. Bilici D, Suleyman H, Banoglu ZN, Kiziltunc A, Avci B, Ciftcioglu A, Bilici S. 2002. Melatonin prevents ethanol-induced gastric mucosal damage possibly due to its antioxidant effect. Dig Dis Sci 47: 856-861. https://doi.org/10.1023/A:1014764705864
  3. Covacci A, Telford JL, Del Giudice G, Parsonnet J, Rappuoli R. 1999. Helicobacter pylori virulence and genetic geography. Science 284: 1328-1333. https://doi.org/10.1126/science.284.5418.1328
  4. Kim JH, Kim HY, Kim NY, Kim SW, Kim JG, Kim JJ, Roe IH, Seo JK, Sim JG, Ahn H, Yoon BC, Lee SW, Lee YC, Chung IS, Jung HY, Hong WS, Choi KW. 2001. Seroepidemiological study of Helicobacter pylori infection in asymptomatic people in South Korea. J Gastroenterol Hepatol 16: 969-975. https://doi.org/10.1046/j.1440-1746.2001.02568.x
  5. Kim MS, Kim N, Kim SE, Jo HJ, Shin CM, Lee SH, Park YS, Hwang JH, Kim JW, Jeong SH, Lee DH, Kim JM, Jung HC. 2013. Long-term follow-up Helicobacter pylori reinfection rate and its associated factors in Korea. Helicobacter 18: 135-142. https://doi.org/10.1111/hel.12018
  6. Bujanda L. 2000. The effects of alcohol consumption upon the gastrointestinal tract. Am J Gastroenterol 95: 3374-3382. https://doi.org/10.1111/j.1572-0241.2000.03347.x
  7. Szabo S, Trier JS, Brown A, Schnoor J. 1985. Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology 88: 228-236. https://doi.org/10.1016/S0016-5085(85)80176-1
  8. Liu ES, Cho CH. 2000. Relationship between ethanol-induced gastritis and gastric ulcer formation in rats. Digestion 62: 232-239. https://doi.org/10.1159/000007821
  9. Chew CS. 1991. Intracellular mechanisms in control of acid secretion. Curr Opin Gastroenterol 7: 856-862. https://doi.org/10.1097/00001574-199112000-00004
  10. Mardh S, Song YH, Carlsson C, Bjorkman T. 1987. Mechanisms of stimulation of acid production in parietal cells isolated from the pig gastric mucosa. Acta Physiol Scand 131: 589-598. https://doi.org/10.1111/j.1748-1716.1987.tb08280.x
  11. Chew C. 1993. Peptidergic regulation of gastric acid secretion. In Gastrointestinal Regulatory Peptides. Springer, Berlin, Heidelberg, Germany. p 199-252.
  12. Helander HF, Keeling DJ. 1993. Cell biology of gastric acid secretion. Baillieres Clin Gastroenterol 7: 1-21. https://doi.org/10.1016/0950-3528(93)90029-R
  13. Uedo N, Takeuchi Y, Yamada T, Ishihara R, Ogiyama H, Yamamoto S, Kato M, Tatsumi K, Masuda E, Tamai C, Yamamoto S, Higashino K, Iishi H, Tatsuta M. 2007. Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer: a prospective randomized controlled trial. Am J Gastroenterol 102: 1610-1616. https://doi.org/10.1111/j.1572-0241.2007.01197.x
  14. Benhammou N, Bekkara FA, Panovska TK. 2008. Antioxidant and antimicrobial activities of the Pistacia lentiscus and Pistacia atlantica extracts. Afr J Pharm Pharmacol 2: 22-28.
  15. Giaginis C, Theocharis S. 2011. Current evidence on the anticancer potential of chios mastic gum. Nutr Cancer 63: 1174-1184. https://doi.org/10.1080/01635581.2011.607546
  16. Kaliora AC, Stathopoulou MG, Triantafillidis JK, Dedoussis GV, Andrikopoulos NK. 2007. Alterations in the function of circulating mononuclear cells derived from patients with Crohn's disease treated with mastic. World J Gastroenterol 13: 6031-6036. https://doi.org/10.3748/wjg.13.6031
  17. Mahmoudi M, Ebrahimzadeh MA, Nabavi SF, Hafezi S, Nabavi SM, Eslami SH. 2010. Antiinflammatory and antioxidant activities of gum mastic. Eur Rev Med Pharmacol Sci 14: 765-769.
  18. Takahashi K, Fukazawa M, Motohira H, Ochiai K, Nishikawa H, Miyata T. 2003. A pilot study on antiplaque effects of mastic chewing gum in the oral cavity. J Periodontol 74: 501-505. https://doi.org/10.1902/jop.2003.74.4.501
  19. Triantafyllou A, Chaviaras N, Sergentanis TN, Protopapa E, Tsaknis J. 2007. Chios mastic gum modulates serum biochemical parameters in a human population. J Ethnopharmacol 111: 43-49. https://doi.org/10.1016/j.jep.2006.10.031
  20. Triantafyllou A, Bikineyeva A, Dikalova A, Nazarewicz R, Lerakis S, Dikalov S. 2011. Anti-inflammatory activity of chios mastic gum is associated with inhibition of TNF-alpha induced oxidative stress. Nutr J 10: 64. https://doi.org/10.1186/1475-2891-10-64
  21. Kottakis F, Kouzi-Koliakou K, Pendas S, Kountouras J, Choli-Papadopoulou T. 2009. Effects of mastic gum Pistacia lentiscus var. Chia on innate cellular immune effectors. Eur J Gastroenterol Hepatol 21: 143-149. https://doi.org/10.1097/MEG.0b013e32831c50c9
  22. Al-Said MS, Ageel AM, Parmar NS, Tariq M. 1986. Evaluation of mastic, a crude drug obtained from Pistacia lentiscus for gastric and duodenal anti-ulcer activity. J Ethnopharmacol 15: 271-278. https://doi.org/10.1016/0378-8741(86)90165-0
  23. Al-Habbal MJ, Al-Habbal Z, Huwez FU. 1984. A doubleblind controlled clinical trial of mastic and placebo in the treatment of duodenal ulcer. Clin Exp Pharmacol Physiol 11: 541-544. https://doi.org/10.1111/j.1440-1681.1984.tb00864.x
  24. Nakada SL, Crothers JM Jr, Machen TE, Forte JG. 2012. Apical vacuole formation by gastric parietal cells in primary culture: effect of low extracellular $Ca^{2+}$. Am J Physiol Cell Physiol 12: 1301-1311
  25. Gioxari A, Kaliora AC, Papalois A, Agrogiannis G, Triantafillidis JK, Andrikopoulos NK. 2011. Pistacia lentiscus resin regulates intestinal damage and inflammation in trinitrobenzene sulfonic acid-induced colitis. J Med Food 14: 1403-1411. https://doi.org/10.1089/jmf.2010.0240
  26. Papalois A, Gioxari A, Kaliora AC, Lymperopoulou A, Agrogiannis G, Papada E, Andrikopoulos NK. 2012. Chios mastic fractions in experimental colitis: implication of the nuclear factor $\kappa$B pathway in cultured HT29 cells. J Med Food 15: 974-983. https://doi.org/10.1089/jmf.2012.0018
  27. Chen D, Zhao CM. 2010. Complexity of gastric acid secretion revealed by targeted gene disruption in mice. Curr Pharm Des 16: 1235-1240. https://doi.org/10.2174/138161210790945904
  28. Schubert ML. 2007. Gastric secretion. Curr Opin Gastroenterol 23: 595-601. https://doi.org/10.1097/MOG.0b013e3282f03462
  29. Osawa H, Kita H, Ohnishi H, Hoshino H, Mutoh H, Ishino Y, Watanabe E, Satoh K, Sugano K. 2006. Helicobacter pylori eradication induces marked increase in $H^+/K^+$-adenosine triphosphatase expression without altering parietal cell number in human gastric mucosa. Gut 55: 152-157. https://doi.org/10.1136/gut.2005.066464
  30. Chadzopulu A, Koukouliata A, Theodosopoulou E, Adraniotis J. 2011. Unique mastic resin from chios. Prog Health Sci 1: 131-136.
  31. Zhou L, Satoh K, Takahashi K, Watanabe S, Nakamura W, Maki J, Hatano H, Takekawa F, Shimada C, Sakagami H. 2009. Re-evaluation of anti-inflammatory activity of mastic using activated macrophages. In Vivo 23: 583-589.

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