Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2021; 27(32): 5392-5403
Published online Aug 28, 2021. doi: 10.3748/wjg.v27.i32.5392
Therapeutic effect of Cistanche deserticola on defecation in senile constipation rat model through stem cell factor/C-kit signaling pathway
Xia Zhang, Fa-Juan Zheng, Zhen Zhang
Xia Zhang, Fa-Juan Zheng, Department of Science and Education, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China
Zhen Zhang, Department of Anorectal, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China
Author contributions: Zhang Z designed the study; Zhang X and Zhang Z wrote the manuscript and were involved in revision, editing and review; Zhang X reformatted the manuscript; Zheng FJ was involved in the animal experiment process and data collation and input; All authors read and approved the final manuscript.
Supported by Natural Science Foundation of Chongqing, No. cstc2017jcyjAX0306.
Institutional animal care and use committee statement: The study was reviewed and approved by the Chongqing Hospital of Traditional Chinese Medicine Ethics Committee, No. Cstc2017jcyjAX0306.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at zhangzhen@cdutcm.edu.cn. Participants gave informed consent for data sharing.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhen Zhang, MD, Deputy Director, Department of Anorectal, Chongqing Hospital of Traditional Chinese Medicine, No. 6 Seventh Branch of Panxi Road, Jiangbei District, Chongqing 400021, China. zhangzhen@cdutcm.edu.cn
Received: April 7, 2021
Peer-review started: April 7, 2021
First decision: May 27, 2021
Revised: June 3, 2021
Accepted: July 20, 2021
Article in press: July 20, 2021
Published online: August 28, 2021
Processing time: 139 Days and 10.8 Hours
Abstract
BACKGROUND

Constipation is one of the chronic gastrointestinal functional diseases. It seriously affects the quality of life. Cistanche deserticola (C. deserticola) can treat constipation obviously, but its mechanism has not been clarified. We supposed that mechanism of it improved the intestinal motility by stimulating interstitial Cajal cells (ICC). Activation of the C-kit receptor on the surface of ICC is closely related to ICC function, and the stem cell factor (SCF)/C-kit signaling pathways plays an important role on it. To investigate the mechanism of how C. deserticola treats constipation, this study aimed to establish a constipation model in rats and explore the role of SCF/C-kit signaling pathway in the treatment.

AIM

To explore the SCF/C-kit signaling pathways in the role of C. deserticola for treatment of constipation by a constipation rat model.

METHODS

Forty-eight 8-mo-old Sprague–Dawley rats were divided into 4 groups by random weight method: Normal group (n = 12), model group (n = 12), C. deserticola group (n = 12) and blocker group (n = 12). The normal group received normal saline by gavage; the model group received loperamide by gavage; the blocker group received loperamide and C. deserticola by gavage, and STI571 was injected by intraperitoneally. During treatment, the weight, fecal granules and fecal quality were recorded every 10 d. On day 20 after model induction, the colon tissues of each group were removed. Hematoxylin and eosin staining was used to observe pathological changes. Expression levels of SCF, C-kit and Aquaporin genes were detected by immunohistochemistry, western blotting, and real-time-quantitative polymerase chain reaction. The colonic epithelial mitochondria and goblet cells were observed by transmission electron microscopy.

RESULTS

Compared with the normal group, as treatment progressed, the weight of rats in the model and blocker groups decreased significantly, the stool weight decreased, and the stool quality was dry (P < 0.05). C. deserticola reversed the decrease in body weight and stool weight and improved stool quality. Histopathological analysis indicated that the colonic mucosal epithelium in the model group was incomplete, and the arrangement of the glands was irregular or damaged. Treatment with C. deserticola improved the integrity and continuity of the epithelial cells and regular arrangement of the glands. The blocking agents inhibited the effects of C. deserticola Immunohistochemistry and real-time-quantitative polymerase chain reaction showed that expression of SCF and C-kit protein or genes in the colonic tissue of the model group was decreased (P < 0.05), while treatment with C. deserticola increased protein or gene expression (P < 0.05). Western blotting showed that expression of aquaporin APQ3 was increased, while the expression of Cx43 decreased in the model group. Treatment with C. deserticola inhibited expression of APQ3 and promoted expression of Cx43. Transmission electron microscopy showed that the mitochondria of the colonic epithelium in the model group were swollen and arranged disorderly, and microvilli were sparse. The condition was better in the C. deserticola group. Mice treated with STI571 blocker confirmed that blocking the SCF/C-kit pathway inhibited the improvement of constipation by C. deserticola.

CONCLUSION

C. deserticola improved defecation in rats with constipation, and the SCF/C-kit signaling pathway, which is a key link of ICC function, played an important role of the treatment.

Keywords: Cistanche deserticola; Senile constipation; Stem cell factors; C-kit

Core Tip: We studied a possible mechanism of Cistanche deserticola (C. deserticola) in the treatment of constipation. The mechanism might improve colon motility through stem cell factor (SCF)/C-kit signaling pathway in colon Cajal stromal cells. Therefore, the constipation rat model was replicated, and then rats were treated by direct administration of C. deserticola and specific blocking of the SCF/C-kit signaling pathway. The defecation of rats, changes of colonic pathology and ultrastructure as well as the protein expression related to the SCF/C-kit signaling pathway were observed. Our results support that the SCF/C-kit signaling pathway plays an important mechanism on the therapeutic effect of C. deserticola.