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JKM > Volume 40(2); 2019 > Article
Lee and Baik: A Comparative Study on the Effects of Pinellia ternata, Zingiber officinale and Sobanhatang on Reflux Esophagitis

Abstract

Objectives

This study was carried out to observe and compare the effects of Pinellia ternata, Zingiber officinale and Sobanhatang on the reflux esophagitis induced by gastric fundus and pylorus ligation in mice with esomeprazole.

Methods

Antioxidant effects were measured by DPPH radical scavenging activity at four different concentration of 0.125, 0.25, 0.5 and 1.0mg/102μℓ. Zingiber officinale water extract(ZE), Pinellia ternata water extract(PE) and Sobanhatang water extract(SBE) and esomeprazole were treated orally for 14 days before gatric fundus and pylorus ligation. In the histochemistry, changes in suface mucous cells, muscle tissue and connective tissue in gastro esophageal junction(GEJ) and mast cell on the esophageal mucosa were observed. The change of Hemo oxygenase(HO)-1, ghrelin, gastrin and substance P in gastric body tissue were measured by immunohistochemistry.

Results

DPPH radical scavenging activity exhibited concentration dependently increases in ZE, PE, SBE. ZE was significantly higher at all concentrations than PE. The gastric surface mucous cells were more in the treated group than in the reflux esophagitis elicited group(GE) in the order of PE, SBE, ZE and esomeprazole treateded group(PT, SBT, ZT, ET). Lower esophageal sphincter muscle damage and intercellular space in the GEJ were less in the treated group than GE. In the esophageal mucosa, the mast cell distribution and the migration of inflammatory cells were lower in the treateded troup than GE in order to ZT, SBT, PT and ET. The antioxidative enzyme, HO-1 was more in the order of ZT, SBT, control group, PT, ET than in GE. ZT was significantly higher than the other groups and SBT was significantly higher than ET. Ghrelin was found to be higher in ZT, ET, SBT and PT than in GE, and ZT was significantly higher than all other groups except ET. Gastrin showed the highest positivity in GE, and was lower in the order of ET, ZT, SBT, PT, and control group. Substance P was the highest in GE, and was lower in the order of ET, ZT, SBT, PT and control group, and PT were significantly lower than ET.

Conclusion

ZT, PT and SBT showed superior antioxidative, anti-inflammatory and mucosal protective effects on mouse reflux esophagitis as compared with ET. In particular, ZE was more effective in antioxidant and gastric motility enhancement, while PE was more effective in mucosal protection and anti-inflammatory effects. Sobanhatang is expected to be effective treatment because it has advantages of both drugs and reduces toxicity.

DPPH radical scavenging activity (%)=(1-absorbanceofsampleabsorbanceofblank)×100

Notes

이 논문은 2017년도 상지대학교 대학원 박사학위 논문임

Fig. 1
Experimental design and reflux esophagitis animal model
HFD, high fat diet; ZE, Zingiber officinale water extract; PE, Pinellia ternata water extract; SBE, Sobanhatang water extract.
jkm-40-2-17f1.gif
Fig. 2
The GC/MS of Component in water extracts of Zingiber officinale, Pinellia ternata, and Sobanhatang
jkm-40-2-17f2.gif
Fig. 3
The free radical scavenging activity of water extracts of Pinellia ternata, Zingiber officinale and Sobanhatang
The anti-oxidant ability of ZE and SBE is dose-dependantly increased and the estimation of SBE is lower compared with ZE. ♦, Pinellia ternata water extract(PE); ■, Zingiber officinale water extract(ZE); ▲, Sobanhatang water extract(SBE); ●, Ascorbic acid as compared anti-oxidant.
jkm-40-2-17f3.gif
Fig. 4
The hemo oxygenase-1 positive reaction in gastric mucosa with reflux esophagitis
Ctrl, no reflux esophagitis elicited group; GE, reflux esophagitis elicited group; ET, esomeprazole treated group before reflux esophagitis elicitation; ZT, Zingiber officinale water extract treated group before reflux esophagitis elicitation; PT, Pinellia ternata water extract treated group before reflux esophagitis elicitation; SBT, Sobanhatang water extract treated group before reflux esophagitis elicitation; Bar size, 100μm; arrow, HO-1 positive reaction; ASM, apical surface of mucosa, LP, lamina propria.
jkm-40-2-17f4.gif
Fig. 5
The ghrelin positive reaction in gastric mucosa with reflux esophagitis
Bar size, 100μm; arrow, ghrelin positive reaction; ASM, apical surface of mucosa, LP, lamina propria.
jkm-40-2-17f5.gif
Fig. 6
The gastrin positive reaction in gastric mucosa with reflux esophagitis
Bar size, 100μm; arrow, gastrin positive reaction; ASM, apical surface of mucosa, LP, lamina propria.
jkm-40-2-17f6.gif
Fig. 7
The substance P positive reaction in gastric mucosa with reflux esophagitis
Bar size, 100μm; arrow, gastrin positive reaction; ASM, apical surface of mucosa, LP, lamina propria
jkm-40-2-17f7.gif
Fig. 8
The protective effect of damaged mucosal barrier by Pinellia ternata water extract, Sobanhatang water extract, Zingiber officinale water extract and esomeprazole
The PAS positive reaction (arrow) in mice pre-treateded with PE, SBE, ZE and esomeprazole noticeably maintain (PAS stain; Bar size, 50μm).
ASM, apical surface of mucosa; LU, lumen.
jkm-40-2-17f8.gif
Fig. 9
The mitigative effect of muscular damage & mucosal inflammation by Pinellia ternata water extract, Sobanhatang water extract, Zingiber officinale water extract and esomeprazole
A photo Bar size, 200μm; B photo Bar size, 50μm, GEJ, gastroesophageal junction; LES, lower esophageal sphincter; ES, esophagus; SM, submucosa; LU, lumen.
jkm-40-2-17f9.gif
Table 1
The Amount and Composition of Sobanhatang
Herbs Scientific Name Amount (g)
生薑 Zingiberis Rhizoma Crudus Zingiber officinale Roscoe 11.25
半夏 Pinellia Rhizoma Pinellia ternata Breitenbach 15.00

Total Amount 26.25
Table 2
The GC/MS of Component in Zingiber officinale water extract
NO RT(min) Area(%) Compounds
1 13.430 44.27 Zingerone
2 19.230 7.84 2-Heptanone
3 19.850 24.57 6-shogaol
4 20.202 23.32 Gingerol

RT, retention time.

Table 3
The GC/MS of Component in Pinellia ternata water extract
NO RT(min) Area(%) Compounds
1 6.395 68.16 Epoxyethane
2 8.921 31.84 Benzaldehyde
Table 4
The GC/MS of Component in Sobanhatang water extract
NO RT(min) Area(%) Compounds
1 6.423 12.52 Cyclopentasiloxane
2 8.921 13.07 Benzaldehyde
3 11.066 8.33 Isobutylamine
4 13.430 66.09 Zingerone
Table 5
DPPH Radical Scavenging Activity of Water Extracts of Pinellia ternata, Zingiber officinale and Sobanhatang Scavenging activity (%)
Concentration PE (mean±SD) ZE (mean±SD) SBE (mean±SD) p value*
1.0 mg 18.89±1.81b 66.49±2.26a 30.31±1.76a,b 0.000
0.5 mg 14.38±1.31b 46.44±3.10a 23.88±1.64a,b 0.000
0.25 mg 9.49±1.06b 29.68±3.53a 15.92±1.08a,b 0.000
0.125 mg 5.18±1.28b 16.05±2.83a 9.61±1.24a,b 0.000

PE, Pinellia ternata water extract; ZE, Zingiber officinaele water extract; SBE, Sobanhatang water extract;

a,b a and b are groups separated by Bonferroni correction method, and represent the same group, respectively.

* Statical significance was determined by Kruskal-Wallis test.

Table 6
The Image Analysis for the Hemo Oxygenase-1 Positive Reaction in Gastric Mucosa
Objective Group
Ctrl (mean±SD) GE (mean±SD) ET (mean±SD) ZT (mean±SD) PT (mean±SD) SBT (mean±SD) p value*
Hemo oxygenase-1 12225±2251b 4631±317d 8730±366c,d 43866±3023a 10082±1214b,c 22876±2025b 0.000

(image analysis for 20.000,000 particles/range of intensity : 80–100)

Ctrl, no reflux esophagitis elicited group; GE, reflux esophagitis elicited group; ET, esomeprazole treated group before reflux esophagitis elicitation; ZT, Zingiber officinale water extract treated group before reflux esophagitis elicitation; PT, Pinellia ternata water extract treated group before reflux esophagitis elicitation; SBT, Sobanhatang water extract treated group before reflux esophagitis elicitation;

a,b,c,d a, b, c and d are groups separated by Bonferroni correction method, and represent the same group, respectively.

* Statical significance was determined by Kruskal-Wallis test.

Table 7
The Image Analysis for the Ghrelin Positive Reaction in Gastric Mucosa
Objective Group
Ctrl (mean±SD) GE (mean±SD) ET (mean±SD) ZT (mean±SD) PT (mean±SD) SBT (mean±SD) p value*
Ghrelin 21888±1469c,d 18008±1077d 56342±2276a,b 59743±1704a 33323±1907b,c,d 47361±3862b,c 0.000

(image analysis for 20.000,000 particles/range of intensity : 80–100)

Table 8
The Image Analysis for the Gastrin Positive Reaction in Gastric Mucosa
Objective Group
Ctrl (mean±SD) GE (mean±SD) ET (mean±SD) ZT (mean±SD) PT (mean±SD) SBT (mean±SD) p value*
Gastrin 13897±1463d 97618±5148a 88260±1991a,b 78867±2963a,b,c 57045±1962c,d 66541±2351b,c,d 0.000

(image analysis for 20.000,000 particles/range of intensity : 80–100)

Table 9
The Image Analysis for the Substance P Positive Reaction in Gastric Mucosa
Objective Group
Ctrl (mean±SD) GE (mean±SD) ET (mean±SD) ZT (mean±SD) PT (mean±SD) SBT (mean±SD) p value*
Substance P 6498±535d 73238±3667a 53105±1580a,b 49622±2138a,b,c 15515±1332c,d 29171±1999b,c,d 0.000

(image analysis for 20.000,000 particles/range of intensity : 80–100)

참고문헌

1. The Korean Society of Neurogastroenterloy and Motility. gastroesophageal reflux disease. Seoul: Korean Med Publisher;2009. p. 2–22.


2. National Professors of Bikye Internal Medicine. Bikye Internal Medicine. Seoul: Kunja Publisher;2009. p. 314–8.


3. Kim JR. 2nd Kim’s Digestive Diseases. Seoul: Ilchokak;2008. p. 158–70.


4. Malfertheiner P, Hallerback B. Clinical manifestations and complications of gastroesophgeal reflux disease(reflux esophagitis). Int J Clin Pract. 2005; 59:3. 346–355.


5. Jiménez P, Piazuelo E, Sánchez MT, Ortego J, Soteras F, Lanas A. Free racicals and antioxidant systerms in reflux seophagitis and Barrett’s esophagus. World J Gastroenterol. 2005; 11:18. 2697–703.


6. Harris RA, Kuppermann M, Richter JE. Prevention of recurrences of erosive reflux esophagitis: a cost-effectiveness analysis of maintenance proton pump inhibition. Am J Med. 1997; 102:1. 78–88.


7. Kim JU, Kim HS, Lee DG, Seog GT, Kim JM, Baik SG, et al. Therapeutic Effect of Low-Dose Omeprazole vs. Standard-Dose Ranitidine in Mild to Moderate Reflux Esophagitis. Korean J of Gastroenterology. 2004; 43:3. 153–9.


8. Jang MW, Lim SW. Experimental Study for Effect of Banhasasim-tang on Mice with Reflux Esophagitis. J Int Korean Med. 2013; 34:4. 362–74.


9. Hwang JY, Kim DJ, Byeon JS. Effects of Yijin-tang-gamibang Extracts on Reflux Esophagitis. J Physiol & Pathol Korean Med. 2009; 23:5. 1073–1079.


10. Park K, Gwak MA, Kim DJ, Byeon JS. Protective Effects of Yijin-tang-gamibang Aqueous Extracts on Reflux Esophagitis Mediated by Antioxidant Defense Systems. J Physiol & Pathol Korean Med. 2010; 24:3. 416–425.


11. Lee ST, Gwak MA. Effects of Individual Herbal Components of Yijintang-gamibang in the Rat Reflux Esophagitis. J Int Korean Med. 2013; 34:2. 165–177.


12. Hur JL. Esophageal Protective Effects of Yijintanggamibanggamoryo. Unpublished doctoral dissertation. Daegu Haany University;2011.


13. Lee YJ, Park JH, No SS. Effects on Rats with Reflux Esophagitis Treated with Lonicerae Flos Extract. J Physiol & Pathol Korean Med. 2010; 24:6. 970–975.


14. Kim DJ, No SS. Effect on Acute reflux Esophagitis by Evodiae Fructus Aquous Extract. Kor J Herbol. 2013; 27:1. 51–58.


15. Sin MH, Kim ES, Lee YS. Suppressive Effects of Ulmi Pumilae Cortex Extracts on the Reflux Esophagitis in Rat. J Physiol & Pathol Korean Med. 2016; 30:4. 257–265.


16. National Professors of Herbology. Herbology. Seoul: Younglimsa;2000. p. 487–8. p. 172–3.


17. Kang BS, kim YP. Practical Combined Herbology. Seoul: Younglimsa;1996. p. 464–6. p. 572–4. p. 771


18. Chae JS. Sanghannonyeokjeon. Seoul: Gomoonsa;1984. p. 468–9.


19. Blois MS. Antioxidant determination by the use of a stable free radical. Nature. 1958; 181:1199–1200.


20. Nakamura K, Ozawa Y, Furuta Y, Omd Miyazaki H. Effects of sodiumpolyacrylate (PANa) on acute esophagitis by gastric juice in rats. Japan J Pharmacol. 1982; 32:3. 445–456.


21. Kurt J. Isselbacher Harrison’s Principles of Internal Medicine. Seoul: Jungdam;1997. p. 1462–3.


22. Lee JS, Oh TY, Ahn BO, Cho H, Kim WB, Kim YB, et al. Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett’s esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants. Mutat Res. 2001; Sep. 1. 480–481:189–200.


23. Wetscher GJ, Perdikis G, Kretchmar DH, Stinson RG, Baqchi D, Redmond EJ, et al. Esophagitis in sprague, dawley rats is mediated by free radicals. Diq Dis Sci. 1995; 40:6. 1297–1305.


24. Kim JJ, Lee SY, Lee PR, Myoung SJ, Kim JH, Choi YK, et al. Multicenter Study to Evaluate the Effect of Esomeprozole in Gastro-esophageal Reflux Disease. Journal of Neurogastroenterology and Motility. 2003; 9:2. 92–101.


25. Tielemans Y, Hakanson R, Sundler F, Willems G. Proliferation of enterochromaffinlike cells in omeprazole-treateded hypergastrinemic rats. Gastroenterology. 1989; 96:2. 723–729.


26. National Professors of Herbal Frmula. Herbal Frmula. Seoul: Younglimsa;1999. p. 400


27. Korea Institute of Korean Medicine. A study of Processed Pinellia ternata. Korea Institute of Korean Medicine Reports. 2001. p. 1–23.


28. Seo BI, Choi HY. Clinical oriental medicine galenic pharmacy. Seoul. 2004; 72–99.


29. Kim SH, Lim HB. Antiasthmatic effects on Pinellia ternate Breitenbach(PTB) water extracts against airway inflammation and hyperresponsiveness induced by diesel exhaust particles with ovalbumin sensitization in BALB/c mice. Kor J Herbology. 2013; 28:1. 65–71.


30. Jung YS, Park SJ, Park JH, Jee GH, Lee IS, Yang SA. Effects of Ethanol Extracts from Zingiber officinale Rosc., Curcuma longa L., and Curcuma aromatica Salisb. on Acetylcholinesterase and Antioxidant Activities as well as GABA Contents. J Korean Soc Food Sci Nutr. 2012; 41:10. 1395–1401.


31. Bae JS, Kim TH. Pancreatic lipase inhibitory and antioxidant activities of Zingiber officinale water extracts. Korean J Food Preserv. 2011; 18:3. 390–396.


32. Gwak JS, Baik JE, Jung SW, Kim JH, Kim JY, Kweon OR. Systematic review of the effect of dried ginger powder on improvement of nausea and vomiting associated with early pregnancy or motion sickness. Journal of Nutrition and Health. 2014; 47:1. 45–50.


33. Kim SJ. Inhibitory Effects of Ginger and Processed (Beopje) Ginger Extracts on HCl-ethanol Induced Gastritis in Rats. J Korean Soc Food Sci Nutr. 2012; 41:11. 1528–1533.


34. Im DY. Volatile compounds analysis of the water extract from dried bark of prunus sargentii and physiological activity of the main compound, benzaldehyde. Kor J Aesthet Cosmetol. 2014; 12:2. 155–162.


35. De Hertogh G, Ectors N, Van Eyken P, Geboes K. Review article: the nature of oesophageal injury in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2006; 24:Suppl2. 17–26.


36. Kim JH, Jee SR, Park SJ, Yang SY, Park ET, Lee YJ, et al. Dilated Intercellular Spaces of Esophageal Epithelium in Korean Reflux Esophagitis and Its Reversibility after Esomeprazole Treatment. Journal of Neurogastroenterology and Motility. 2006; 12:1. 19–24.


37. Weber A, Knop J, Maurer M. Pattern analysis of human cutaneous mast cell populations by total body surface mapping. Br J Dermatol. 2003; 148:2. 224–228.


38. Kim YH. The Role of Mast Cells in Innate and Adaptive Immunity. Journal of Life Science. 2008; 18:6. 891–896.


39. Brown JM, Wilson TM, Metcalfe DD. The mast cell and allergic diseases: Role in pathogenesis and implications for therapy. Clin Exp Allergy. 2008; 38:1. 4–18.


40. Boesiger J, Tsai M, Maurer M, Yamaguchi M, Brown LF, Claffey KP, et al. Mast cells can secrete vascular permeability factor/vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of fc epsilon receptor I expression. J Exp Med. 1998; 188:6. 1135–1145.


41. Park JH, Kweon GR. Clinical applications of antioxidants. Hanyang Med Rev. 2013; 33:130–136.


42. Schipper HM. Heme oxygenase-1: role in brain aging and neurodegeneration. Exp Gerontol. 2000; 35:6–7. 821–30.


43. Nakao A, Otterbein LE, Overhaus M, Sarady JK, Tsung A, Kimizuka K, et al. Biliverdin protects the functional integrity of a transplanted syngeneic small bowel. Gastroenterology. 2004; 127:2. 595–606.


44. Kim EH, Kim SH, Na HK, Surh YJ. Chemoprevention and Chemoprotection Through Heme Oxygenase-1 Induction and Underlying Molecular Mechanisms. Journal of Korea Environmental Mutagen Society. 2006; 26:4. 97–112.


45. Gnanapavan S, Kola B, Bustin SA, et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab. 2002; 87:6. 2988–2991.


46. Tschop M, Flora DB, Mayer JP, Heiman ML. Hypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats. Obes Res. 2002; 20:20. 991–999.


47. Dixit VD, Schaffer EM, Pyle RS, et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest. 2004; 114:1. 57–66.


48. Konturek SJ, Konturek PC, Pawlik T, Sliwowski Z, Ochmańki W, Hahn EG. Duodenal mucosal protection by bicarbonate secretion and its mechanisms. J Physiol Pharmacol. 2004; 55:suppl 2. 5–17.


49. Schubert ML. Gastric secretion. Curr Opin Gastroenterol. 2010; 26:6. 598–603.


50. Ceranowicz P, Warzecha Z, Dembinski A, et al. treatedment with ghrelin accelerates the healing of acetic acid-induced gastric and duodenal ulcers in rats. J Physiol Pharmacol. 2009; 60:1. 87–98.


51. Warzecha Z, Ceranowicz P, Dembinski M, et al. Involvement of cyclooxygenase-1 and cyclooxygenase-2 activity in the therapeutic effect of ghrelin in the course of ethanol-induced gastric ulcers in rats. J Physiol Pharmacol. 2014; 65:1. 95–106.


52. Kim BW, Lee BI, Kim HG, Jo YS, Chae HS, Lee HK, et al. Influence of Long-term Gastric Acid Suppression Therapy on the Expression of Serum Gastrin, Chromogranin A, and Ghrelin. Korean Journal of Gastroenterology. 2009; 53:2. 84–89.


53. Lee JK. Gastrointestinal Hormones and Digestion. Korean J Pancreas Biliary Tract. 2014; 19:Suppl 1. 29–33.


54. Kim JS, Lee SJ. Effect of Pylorus Ligation on Serum Gastrin Release and Gagtric Secretion in the Rat. Korean Journal of Medicine. 1981; 24:8. 730–737.


55. Ebner K, Singewald N. The role of substance P in stress and anxiety responses. Amino Acids. 2006; 31:3. 251–72.


56. Seo SC, Kim MS, Park BK, Park SM, Kim JS. An Experimental Study on the Effects of Substance P on Gastric Secretion in Rats. Korean Journal of Gastroenterology. 1982; 14:2. 13–16.


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