Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Effect of atractylenolide III on interstitial cells of Cajal and C-kit/SCF pathway of rats with loperamide-induced slow transit constipation

Wang Hao¹, Gong Yuxia¹, Li Youran¹, Xu Minmin¹, Gu Yunfei²

¹Department of Anorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine; ²Department of Anorectal Surgery, Nanjing University of Chinese Medicine, Qinhuai District, Nanjing City, China.

For correspondence:- Gu Yunfei Email: h75tdu@163.com

Accepted: 27 May 2019 Published: 30 June 2019

Citation: Hao W, Yuxia G, Youran L, Minmin X, Yunfei G. Effect of atractylenolide III on interstitial cells of Cajal and C-kit/SCF pathway of rats with loperamide-induced slow transit constipation. Trop J Pharm Res 2019; 18(6):1197-1204 doi: 10.4314/tjpr.v18i6.8

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To determine the effect of atractylenolide-III (ATL-III) on loperamide-induced slow transit constipation (STC) in a rat STC model, and to elucidate the mechanisms involved.

Methods: Male Wistar rats were divided into five groups (n=6 per group): normal control group (NG), model group, and three STC rat groups treated with different doses of ATL-III, viz, 5, 10 and 15 mg/kg. The rats were treated for 15 days. Feed consumption, fecal excretion and intestinal transit rate were determined. Nitric oxide synthase (NOS), somatostatin (SS), serotonin (5-HT), and vasoactive intestinal peptide (VIP) were measured with enzyme-linked immunosorbent assay (ELISA). The protein and mRNA expressions of C-kit, SCF, PKC, and PI-3K were assayed using Western blot analysis and real-time reverse transcription polymerase chain reaction (RT-PCR), respectively.

Results: The amount, weight, and moisture content of stool, and water consumption were significantly higher in ATL-III-treated groups than in the untreated (model) group (p < 0.05), whereas no difference was observed in feed intake. Intestinal transit rate was higher in the ATL-III-treated groups (p < 0.05). Decreased NOS, SS and VIP levels and increased 5-HT level were seen in the ATL-III-treated groups (p < 0.05). ATL-III treatment also induced increases in smooth muscle cells, neuronal cells, and mucous layer (p<0.05). Results from RT-PCR and Western blot revealed that ATL-III–treated groups had elevated c-kit, SCF, PKC, as well as PI-3K mRNA and protein expressions (p < 0.05).

Conclusion: These results suggest that ATL-III mitigates loperamide-induced STC in rats via stimulation of NOS, SS, VIP, and 5-HT secretions. It also increases smooth muscle cells, neuronal cells, and mucous layer, and regulates the signaling pathways involving PKC, PI3K, SCF, and c-kit.

Keywords: Slow transit constipation, Atractylenolide III, Interstitial cells of Cajal, Smooth muscle cells, Neuronal cells, Mucous layer