Abstract

Several natural products containing tannins are used as traditional medicines for treatment of constipation; however, their pharmacological mechanism is not well understood. The laxative effects of gallotannin-enriched extract isolated from Galla Rhois (GEGR) were investigated using a constipation model induced by loperamide (Lop) injection. After analysis for antioxidant activity of GEGR, alterations in the excretion parameters, histological structure, mucin secretion, and related protein levels were measured in the transverse colon of Sprague Dawley (SD) rats with Lop-induced constipation following treatment with 250, 500 and 1,000 mg/ml of GEGR. The number and weight of feces increased significantly by 48–79% and 128–159%, respectively, in the Lop+GEGR treated group relative to the Lop+vehicle treated group, while food intake and water consumption were maintained at a constant level. The thickness of mucosa, muscle and flat luminal surface, as well as the number of goblet cells and crypt of lieberkuhn were enhanced in the Lop+GEGR treated group. Moreover, mucin secretion increased significantly in a dose dependent manner in the Lop+GEGR treated group. Furthermore, the downstream signaling pathway of the muscarinic acetylcholine receptors (mAChR) M2 and M3 was recovered by GEGR treatment, although the expression level varied. The levels of Gα expression and inositol triphosphate (IP3) concentration were also recovered in the Lop+GEGR treated group relative to the Lop+vehicle treated group. The results of the present study provide strong evidence that tannins distributed in various medicinal plants are important candidates for improving chronic constipation induced by Lop treatment in animal models.

Highlights

  • Constipation is an acute or chronic gastrointestinal disease characterized by infrequent bowel movements, hard and dry feces, incomplete bowel evacuation and difficulty during defecation [1]

  • The laxative effects of Galla Rhois (GR, accounting for more than 98% of tannins) on the constipation induced by loperamide (Lop) injection have not yet been investigated in Sprague Dawley (SD) rats, even though gallotannin-enriched extract isolated from Galla Rhois (GEGR) has traditionally been used for treatment of diarrhea, several skin diseases, seminal emissions, excessive sweating, abscess, bleeding and chronic cough without any toxicity [10,11]

  • The inhibitory activity against DPPH radical was rapidly increased by the addition of 0.12–32.30 μg/ml of GEGR

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Summary

Introduction

Constipation is an acute or chronic gastrointestinal disease characterized by infrequent bowel movements, hard and dry feces, incomplete bowel evacuation and difficulty during defecation [1]. Chemical drugs (laxatives) such as senna, correctol, exlax, senokot and gaviscon can be prescribed help patients pass feces [2] Most of these laxatives act as stimulants to increase bulkiness and soften stool, or as osmotic agents, enhancing water flow into the colon to promote elimination and trigger bowel movements [3]. Several plant extracts containing tannins have been reported to exhibit laxative activities based on their ability to increase feces number and weight. The laxative effects of Galla Rhois (GR, accounting for more than 98% of tannins) on the constipation induced by loperamide (Lop) injection have not yet been investigated in Sprague Dawley (SD) rats, even though gallotannin-enriched extract isolated from Galla Rhois (GEGR) has traditionally been used for treatment of diarrhea, several skin diseases, seminal emissions, excessive sweating, abscess, bleeding and chronic cough without any toxicity [10,11]. GR was found to exert anticancer activity against nasopharyngeal carcinoma cells [17] and to improve sensory motor function in a transient focal cerebral ischemia rat model [18]

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