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. 2019 Jun;24(2):159-164.
doi: 10.3746/pnf.2019.24.2.159. Epub 2019 Jun 30.

Cudrania tricuspidata Extract Protects against Reflux Esophagitis by Blocking H2 Histamine Receptors

Joo Yun Kim  1 , Sung Sik Jang  1 , Jung Lyoul Lee  1 , Jae-Hun Sim  1 , Jae-Jung Shim  1   2
Affiliations

Cudrania tricuspidata Extract Protects against Reflux Esophagitis by Blocking H2 Histamine Receptors

Joo Yun Kim et al. Prev Nutr Food Sci. 2019 Jun.

Erratum in

  • Correction of MATERIALS AND METHODS.
    [No authors listed] [No authors listed] Prev Nutr Food Sci. 2021 Sep 30;26(3):366. doi: 10.3746/pnf.2021.26.3.366. Prev Nutr Food Sci. 2021. PMID: 34737998 Free PMC article.

Abstract

Cudrania tricuspidata has been used in East Asia as a folk medicine for symptoms such as inflammation, allergy, and gastritis. Administration of C. tricuspidata extract to pylori-ligated rat stomachs reduces gastric acid secretion and alleviates esophagus damage caused by gastric reflux. Therefore, in this study we aimed to investigate whether C. tricuspidata extracts inhibit reflux esophagitis by blocking H2 histamine receptor (H2R). Dimaprit, a H2R specific agonist, induced intracellular cyclic adenosine monophosphate (cAMP) production in U937 cells. Pretreatment with C. tricuspidata extracts significantly blocked dimaprit-induced cAMP production in a concentration-dependent manner. To extracted C. tricuspidata with different ethanol concentrations to determine the optimum method. We found that the 70% ethanol extract showed the most potent H2R antagonistic effect against dimaprit-induced cAMP production. However, water extract did not show any H2R blocking effect. These findings suggest that C. tricuspidata extracted using ethanol specifically inhibits gastric acid secretion and reduces esophageal injury by blocking H2R in a competitive manner. Therefore, C. tricuspidata extracts may be used in food or medicine to prevent H2R-related diseases, such as gastric hyperacidity and reflux esophagitis.

Keywords: Cudrania tricuspidata; H2 histamine receptor; gastric hyperacidity; gastric juice secretion; reflux esophagitis.

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Conflict of interest statement

AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Effect of Cudrania tricuspidata extract on gastric acid secretion. (A) Total gastric juice secretion after pylorus ligature and (B) total acidity of gastric contents from pylorus-ligated rats. Gastric juice was collected immediately after sacrificing the rats, and the total volume and total acidity of gastric secretions were measured. The pylorus-ligated rats were treated with the indicated dose of C. tricuspidata extract. Veh, 0.5% methyl cellulose; Rani, 7.7 mg/kg of ranitidine; 5 mg/kg, 5 mg/kg of C. tricuspidata extract; 10 mg/kg, 10 mg/kg of C. tricuspidata extract; 15 mg/kg, 15 mg/kg of C. tricuspidata extract; 20 mg/kg, 20 mg/kg of C. tricuspidata extract. Values are mean±SE. Significantly different from Veh group at *P <0.05 and **P <0.01.
Fig. 2
Fig. 2
Effect of Cudrania tricuspidata extract on reflux esophagitis. (A) Esophageal lesions and (B) the area ratio of esophageal injury. The esophagus was collected immediately after rats were sacrificed and was cut in the longitudinal direction from the gastroesophageal junction to the pharynx. The dissected esophagus was laid on paper, and photographic images were captured with an optical digital camera. The pylorus- and forestomach-ligated rats were treated with the indicated dose of C. tricuspidata extract. Veh, 0.5% methyl cellulose; Rani, 7.7 mg/kg of ranitidine; 20 mg/kg, 20 mg/kg of C. tricuspidata extract; 50 mg/kg, 50 mg/kg of C. tricuspidata extract. Values are mean±SE. Significantly different from Veh group at **P <0.01.
Fig. 3
Fig. 3
Inhibition of H2 histamine receptor (H2R)-mediated cyclic adenosine monophosphate (cAMP) production by Cudrania tricuspidata extract in U937 cells. (A) C. tricuspidata ethanol extracts inhibit cAMP production in a dose-dependent manner. (B) H2R inhibitory activity of C. tricuspidata extracted with various concentrations of ethanol. U937 cells were pretreated with 10 μM of ranitidine or C. tricuspidata extracts for 5 min. Next, cells were stimulated with 10 μM of dimaprit. The control group was treated with the same amount of DMSO instead of ranitidine or C. tricuspidata extracts. Values are mean±SE. ##P <0.01 indicates a significant difference between the control group and the Dimaprit group. A significant difference between the Dimaprit group and the C. tricuspidata extract groups at *P <0.05 and **P <0.01.
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