Lab Anim Res.  2018 Dec;34(4):223-231. 10.5625/lar.2018.34.4.223.

Regulation of gastrointestinal hormones during laxative activity of gallotannin-enriched extract isolated from Galla Rhois in loperamide-induced constipation of SD rats

• Kim JE
• Kang MJ
• Choi JY
• Park JJ
• Lee MR
• Song BR
• Kim HR
• Park JW
• Choi HJ
• Bae SJ
• Hwang DY

• KMID: 2459299
• DOI: http://doi.org/10.5625/lar.2018.34.4.223

Abstract

Regulation of gastrointestinal hormones have been reported in animal models for constipation undergoing laxative therapy when administered herbal products. We undertook to investigate whether the laxative activity of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) affects the regulation of gastrointestinal hormones, by examining the concentration of four hormones and the activation of their receptors in the loperamide (Lop)-induced constipation model. Stool parameters, including number, weight and water content, were significantly recovered in the Lop+GEGR treated group, relative to the Lop+vehicle treated group; however, food intake and water consumption were maintained at a constant level. Also, a similar recovery was detected for thickness of mucosa, muscle and flat luminal surface in the Lop+GEGR treated group. Furthermore, concentration of the four gastrointestinal hormones evaluated, namely, cholecystokinin (CCK), gastrin (GAS), somatostatin (SS) and motilin (MTL), were lower in the Lop+vehicle treated group than the No treated group, but were remarkably enhanced in the Lop+GEGR treated group. Moreover, the downstream signaling pathway of MTL and SS receptors were recovered after GEGR administration. Results of the present study therefore indicate that the laxative effects of GEGR treatment may be tightly related with the regulation of gastrointestinal hormones in the Lop-induced constipation model.

Keyword

Constipation; Galla Rhois; laxative effect; gastrointestinal hormones; signaling pathway

MeSH Terms

Animals
Cholecystokinin
Constipation*
Drinking
Eating
Gastrins
Gastrointestinal Hormones*
Loperamide
Models, Animal
Motilin
Mucous Membrane
Phenobarbital
Rats*
Somatostatin
Water
Cholecystokinin
Gastrins
Gastrointestinal Hormones
Loperamide
Motilin
Phenobarbital
Somatostatin
Water

Figure

• 

  Figure 1 Alteration of feeding behavior and constipation parameters in Lop+GEGR treated group. (A) Actual image of stools collected from the subset groups. (B) Level of feeding behavior and stool parameters. The number, weight and water content of stools as well as urine volume was measured in No, Lop+vehicle and Lop+QCT treated groups. Food intake and water consumption were also measured during the experiment, as described in material and methods. Five to six rats per group were assayed for stool parameters and feeding behavior analysis. Data represents the mean±SD from three replicates. *P<0.05 compared to the No treated group. #P<0.05 compared to the Lop+vehicle treated group.

• 

  Figure 2 Recovery of histological structure in Lop+GEGR treated group. Transverse colon from the No, Lop+vehicle and Lop+GEGR treated groups were subjected to H&E staining to assess their histological structures. Stained sections were observed at 400× using a light microscope. Histopathological parameters were determined using the Leica Application Suite (Leica Microsystems, Heerbrugg, Switzerland). Data represents the mean±SD of three replicates. *P<0.05 compared to the No treated group. #P<0.05 compared to the Lop+vehicle treated group.

• 

  Figure 3 Alterations in the concentration of MTL and the downstream signaling pathway of its receptor in the transverse colon of Lop+GEGR treated group. (A) The level of MTL was quantified in the transverse colon homogenate by an enzyme-linked immunosorbent assay. The minimum detectable concentration of this kit is 31.25–2,000 pg/mL. (B) The level of IP3 was measured in the transverse colon homogenate by an enzyme-linked immunosorbent assay. The minimum detectable concentration of this kit is 5–1,000 pg/mL. (C) Phosphorylation level of PKC: The expression level of PKC and p-PKC were measured in the transverse colon of Lop+GEGR treated model using specific antibodies. Data represents the mean±SD of three replicates. *P<0.05 compared to the No treated group. #P<0.05 compared to the Lop+vehicle treated group.

• 

  Figure 4 Alterations in the concentration of SS and downstream signaling pathway of its receptors in the transverse colon of Lop+GEGR treated group. (A) The SS concentration was measured in the transverse colon homogenate by an enzyme-linked immunosorbent assay. The minimum detectable concentration of this kit is 1.56–100 pg/mL. (B) The expression levels of Bax, p53, JNK and p-JNK in the downstream signaling pathway of SS receptor were measured in the transverse colon of Lop+GEGR treated model using specific antibodies. Data represents the mean±SD of three replicates. *P<0.05 compared to the No treated group. #P<0.05 compared to the Lop+vehicle treated group.

• 

  Figure 5 Alterations in the concentration of CCK and GAS in the transverse colon of Lop+GEGR treated group. (A) The CCK concentration was measured in the transverse colon homogenate by an enzyme-linked immunosorbent assay. The minimum detectable concentration of this kit is 0.1–1,000 pg/mL CCK. (B) The GAS concentration was measured in the transverse colon homogenate by an enzyme-linked immunosorbent assay. The minimum detectable concentration of this kit is 0.312–20 pg/mL. Data represents the mean±SD of three replicates. *P<0.05 compared to the No treated group. #P<0.05 compared to the Lop+vehicle treated group.

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