PMID- 37789966
OWN - NLM
STAT- MEDLINE
DCOM- 20231005
LR  - 20231005
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 17
DP  - 2023
TI  - How Tongxie-Yaofang Regulates Intestinal Synaptic Plasticity by Activating 
      Enteric Glial Cells and NGF/TrkA Pathway in Diarrhea-Predominant Irritable Bowel 
      Syndrome Rats.
PG  - 2969-2983
LID - 10.2147/DDDT.S423333 [doi]
AB  - PURPOSE: Diarrhea-predominant irritable bowel syndrome (D-IBS) is a frequent 
      functional gastrointestinal disease that affects health and quality of life owing 
      to its high incidence and recurrence rate. Tongxie-Yaofang (TXYF) is a 
      traditional Chinese medicine prescribed for D-IBS. However, the therapeutic 
      mechanism of TXYF has not been fully elucidated. This study aimed to investigate 
      the effects of TXYF on visceral hypersensitivity in stress-induced D-IBS rats and 
      the underlying mechanisms. METHODS: Electromyographic (EMG) activity of the 
      external oblique muscles and the abdominal withdrawal reflex (AWR) score captured 
      by Barostat were used to quantify the effect of TXYF on visceral sensitivity. 
      Transmission electron microscopy (TEM) was used to observe the ultrastructure of 
      the enteric nervous system (ENS). For molecular detection, the colonic expression 
      of enteric glial cell's (EGC's) activation markers, glial fibrillary acidic 
      protein (GFAP) and calcium-binding protein S100beta, NGF, TrkA, synaptic 
      plasticity-related factors, synaptophysin (SYN) and postsynaptic density-95 
      (PSD-95), glutamate, glutamate receptors 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR), and 
      N-methyl-D-aspartate receptor (NMDAR) were detected by immunohistochemistry, 
      enzyme-linked immunosorbent assay, and real-time PCR. An ex vivo experiment was 
      conducted to measure the EGC-induced NGF release. RESULTS: TXYF decreased the EMG 
      activity and AWR scores in rats with D-IBS. Under TEM, TXYF improved the dense 
      and irregular nerve arrangement, narrowed the synaptic cleft, and decreased the 
      number of synaptic vesicles in D-IBS rats. In addition, TXYF decreased the 
      expression of GFAP, S100beta, SYN, and PSD-95; down-regulated the levels of NGF, 
      TrkA, and glutamate; and reduced the mRNA expression of AMPAR1, NMDAR1, and 
      NMDAR2B. In an ex vivo experiment, TXYF decreased NGF release in D-IBS rats, and 
      this trend disappeared under EGC inhibition. CONCLUSION: TXYF alleviated visceral 
      hypersensitivity in D-IBS rats possibly by improving synaptic plasticity through 
      inhibiting the activity of EGCs and the NGF/TrkA signaling pathway in the colon.
CI  - (c) 2023 Lu and Zhang.
FAU - Lu, Xiaofang
AU  - Lu X
AD  - Center of Digestive, Beijing Hospital of Traditional Chinese Medicine, Capital 
      Medical University, Beijing, People's Republic of China.
FAU - Zhang, Shengsheng
AU  - Zhang S
AD  - Center of Digestive, Beijing Hospital of Traditional Chinese Medicine, Capital 
      Medical University, Beijing, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20230927
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (tongxie-yaofang)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Irritable Bowel Syndrome/drug therapy
MH  - Quality of Life
MH  - Glutamic Acid
MH  - Diarrhea/drug therapy
MH  - Neuroglia/metabolism
MH  - Neuronal Plasticity
PMC - PMC10544122
OTO - NOTNLM
OT  - Tongxie-Yaofang
OT  - diarrhea-predominant irritable bowel syndrome
OT  - enteric glial cell
OT  - synaptic plasticity
OT  - visceral hypersensitivity
COIS- The authors declare that there are no conflicts of interest in this work.
EDAT- 2023/10/04 06:43
MHDA- 2023/10/05 06:44
PMCR- 2023/09/27
CRDT- 2023/10/04 03:57
PHST- 2023/06/20 00:00 [received]
PHST- 2023/09/19 00:00 [accepted]
PHST- 2023/10/05 06:44 [medline]
PHST- 2023/10/04 06:43 [pubmed]
PHST- 2023/10/04 03:57 [entrez]
PHST- 2023/09/27 00:00 [pmc-release]
AID - 423333 [pii]
AID - 10.2147/DDDT.S423333 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2023 Sep 27;17:2969-2983. doi: 10.2147/DDDT.S423333. 
      eCollection 2023.