Huayu Tongbian Decoction promotes efferocytosis of interstitial Cajal cells in rats with slow transit constipation by inhibiting the PI3K/Akt signaling pathway

doi:10.12122/j.issn.1673-4254.2026.02.07

Abstract

Abstract:

Objective To explore the mechanism of Huayu Tongbian Decoction (HYTBD) for relieving slow transit constipation (STC) in rats. Methods Sixty SD rat models of STC induced by intragastric administration of loperamide hydrochloride suspension were randomized equally into 5 groups for treatment with daily gavage with saline (STC model group), low-, medium-, or high-dose HYTBD, or mosapride (positive control group), with another 12 normal rats receiving saline gavage as the blank control group. The first black stool time, fecal water content and intestinal propulsion rate of the rats were measured, and the ultrastructure of interstitial Cajal cells (ICCs) was observed using transmission electron microscopy to calculate the mitochondrial vacuolar rate. The phagocytosis rate of macrophages was detected using immunofluorescence assay, and colonic pathologies were examined using HE staining. The colonic expression levels of c-Kit, CD47, PI3K and Akt were detected with immunohistochemistry or Western Blotting, and their correlations with efferocytosis were analyzed. Results The rat models of STC showed significant ultrastructural damage of the ICCs with increased first black stool time, mitochondrial vacuolar rate, and colonic expression levels of CD47, p-PI3K/PI3K and p-Akt/Akt proteins, lowered fecal water content, intestinal propulsion rate and c-Kit expression level, without significant changes in phagocytic rate. Treatment with HYTBD, especially at the high dose, significantly increased fecal water content, intestinal propulsion rate, phagocytosis rate and colonic c-Kit expression, and decreased the first black stool time, mitochondrial vacuolar rate, and colonic expressions of CD47, p-PI3K/PI3K and p-Akt/Akt in the mouse models. Conclusion HYTBD improves STC in rats possibly by down-regulating colonic CD47 expression and improving macrophage phagocytosis rate via inhibiting PI3K and Akt phosphorylation, thereby promoting efferocytosis of the ICCs.

Key words: Huayu Tongbian Decoction, efferocytosis, slow transit constipation, PI3K/Akt signaling pathway, interstitial Cajal cells

Jiahui QIU, Meng CHEN, Ru MAN, Xin CHEN, Dongrui QIU, Qitong CHANG, Hongyu MA. Huayu Tongbian Decoction promotes efferocytosis of interstitial Cajal cells in rats with slow transit constipation by inhibiting the PI3K/Akt signaling pathway[J]. Journal of Southern Medical University, 2026, 46(2): 293-300.

Figures/Tables 11

References 35

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Group	Before modeling	After modeling	After treatment
Control	212.15±1.20	248.86±3.48	309.82±5.85
Model	213.67±3.67	231.83±1.56**	267.00±2.81**
LH	210.77±3.81	230.05±2.17**	272.54±6.19**
MH	208.41±2.94	230.11±2.53**	284.46±6.37**^#
HH	210.87±2.50	230.66±2.13**	297.07±5.14^##
Positive drug	208.04±2.53	227.84±1.61**	291.82±8.19*^##

Group	Before modeling	After modeling	After treatment
Control	212.15±1.20	248.86±3.48	309.82±5.85
Model	213.67±3.67	231.83±1.56**	267.00±2.81**
LH	210.77±3.81	230.05±2.17**	272.54±6.19**
MH	208.41±2.94	230.11±2.53**	284.46±6.37**^#
HH	210.87±2.50	230.66±2.13**	297.07±5.14^##
Positive drug	208.04±2.53	227.84±1.61**	291.82±8.19*^##

Group	Fecal water content (%)	First black stool time (min)	Intestinal propulsion rate (%)
Control	55.11±1.17	186.20±3.59	80.37±2.61
Model	26.71±0.63**	302.20±10.13**	48.20±1.15**
LH	29.40±1.17**	288.70±8.63**	51.83±1.93**
MH	42.73±1.20**^##	260.70±6.68**^##	66.50±2.01**^##
HH	52.25±1.31^##	198.30±11.43^##	76.07±1.74^##
Positive drug	44.17±1.00**^##	246.20±6.26**^##	66.90±1.57**^##

Group	Fecal water content (%)	First black stool time (min)	Intestinal propulsion rate (%)
Control	55.11±1.17	186.20±3.59	80.37±2.61
Model	26.71±0.63**	302.20±10.13**	48.20±1.15**
LH	29.40±1.17**	288.70±8.63**	51.83±1.93**
MH	42.73±1.20**^##	260.70±6.68**^##	66.50±2.01**^##
HH	52.25±1.31^##	198.30±11.43^##	76.07±1.74^##
Positive drug	44.17±1.00**^##	246.20±6.26**^##	66.90±1.57**^##

Group	Mitochondrial vacuolation rate (%)
Control	15.15±0.93
Model	69.28±4.81**
LH	64.88±1.18**
MH	59.26±3.76**^#
HH	34.01±2.99**^##
Positive drug	45.98±1.21**^##