Basic Study
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World J Gastroenterol. Feb 21, 2021; 27(7): 576-591
Published online Feb 21, 2021. doi: 10.3748/wjg.v27.i7.576
Xiangbinfang granules enhance gastric antrum motility via intramuscular interstitial cells of Cajal in mice
Qi-Cheng Chen, Zhi Jiang, Jun-Hong Zhang, Li-Xing Cao, Zhi-Qiang Chen
Qi-Cheng Chen, Zhi Jiang, Li-Xing Cao, Zhi-Qiang Chen, The Research Team of TCM Applications of Perioperative, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, Guangdong Province, China
Jun-Hong Zhang, Department of Research Public Service Center, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, Guangdong Province, China
Author contributions: Chen QC, Cao LX and Chen ZQ designed the research study; Chen QC, Jiang Z and Zhang JH performed the research; Chen QC analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Supported by The Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine, No. YN10101902; and the National Regional Traditional Chinese Medicine (Specialist) Clinic Construction, No. (2018)205.
Institutional review board statement: The study was reviewed and approved by the Institutional Animal Care and Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine (approval No. 2018003).
Institutional animal care and use committee statement: All animal procedures were conducted according to the Regulations for the Care and Use of Laboratory Animals in Guangzhou University of Chinese Medicine.
Conflict-of-interest statement: The authors declare that there is no conflict of interest in this study.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at wssq@gzucm.edu.cn.
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: Zhi-Qiang Chen, MD, Professor, The Research Team of TCM Applications of Perioperative, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, No. 111 Dade Road, Guangzhou 510120, Guangdong Province, China. wssq@gzucm.edu.cn
Received: October 27, 2020
Peer-review started: October 27, 2020
First decision: December 13, 2020
Revised: December 24, 2020
Accepted: January 13, 2021
Article in press: January 13, 2021
Published online: February 21, 2021
Abstract
BACKGROUND

Interdigestive migrating motor complexes (MMC) produce periodic contractions in the gastrointestinal tract, but the exact mechanism of action still remains unclear. Intramuscular interstitial cells of Cajal (ICC-IM) participate in gastrointestinal hormone and neuromodulation, but the correlation between ICC-IM and MMC is also unclear. We found that xiangbinfang granules (XBF) mediated the phase III contraction of MMC. Here, the effects of XBF on gastric antrum motility in W/Wv mice and the effects of ICC-IM on gastric antrum MMC are reported.

AIM

To observe the effects of ICC-IM on gastric antrum motility and to establish the mechanism of XBF in promoting gastric antrum motility.

METHODS

The density of c-kit-positive ICC myenteric plexus (ICC-MP) and ICC-IM in the antral muscularis of W/Wv and wild-type (WT) mice was examined by confocal microscopy. The effects of XBF on gastric antrum slow waves in W/Wv and WT mice were recorded by intracellular amplification recording. Micro-strain-gauge force transducers were implanted into the gastric antrum to monitor the MMC and the effect of XBF on gastric antrum motility in conscious W/Wv and WT mice.

RESULTS

In the gastric antrum of W/Wv mice, c-kit immunoreactivity was significantly reduced, and no ICC-IM network was observed. Spontaneous rhythmic slow waves also appeared in the antrum of W/Wv mice, but the amplitude of the antrum slow wave decreased significantly in W/Wv mice (22.62 ± 2.23 mV vs 2.92 ± 0.52 mV, P < 0.0001). MMCs were found in 7 of the 8 WT mice but no complete MMC cycle was found in W/Wv mice. The contractile frequency and amplitude index of the gastric antrum were significantly increased in conscious WT compared to W/Wv mice (frequency, 3.53 ± 0.18 cpm vs 1.28 ± 0.12 cpm; amplitude index, 23014.26 ± 1798.65 mV·20 min vs 3782.16 ± 407.13 mV·20 min; P < 0.0001). XBF depolarized smooth muscle cells of the gastric antrum in WT and W/Wv mice in a dose-dependent manner. Similarly, the gastric antrum motility in WT mice was significantly increased after treatment with XBF 5 mg (P < 0.05). Atropine (0.1 mg/kg) blocked the enhancement of XBF in WT and W/Wv mice completely, while tetrodotoxin (0.05 mg/kg) partially inhibited the enhancement by XBF.

CONCLUSION

ICC-IM participates in the regulation of gastric antrum MMC in mice. XBF induces MMC III-like contractions that enhance gastric antrum motility via ICC-IM in mice.

Keywords: Interstitial cells of Cajal, Migrating motor complex, W/Wv, Gastric antrum motility, Xiangbinfang granules, Chinese medicine

Core Tip: This study shows that intramuscular interstitial cells of Cajal (ICC-IM) play crucial roles in regulating the activity of gastric antral migrating motor complexes (MMC). This may be an important bridge between the vagus, enteric nervous system and motilin to regulate smooth muscle contraction. Through the muscarinic receptor pathway on ICC-IM, the Chinese medicine Xiangbinfang granules depolarize smooth muscle cells and initiates an action potential, changing the periodic motion of MMC into a phase III-like contraction pattern in the gastric antrum of mice.