Hezhong Xiaopi Granules Regulate Ncln-CHOP Axis to Inhibit Endoplasmic Reticulum Stress and Reduce Gastric Mucosal Cell Apoptosis
10.13422/j.cnki.syfjx.20260193
- VernacularTitle:和中消痞颗粒调控Ncln-CHOP轴抑制内质网应激减轻胃黏膜细胞凋亡的机制
- Author:
Hongzheng LI
1
;
Shaoli WANG
2
;
Zucheng SHANG
2
;
Mengfan LI
3
;
Zhen LIU
2
Author Information
1. Postdoctoral Research Center， China Academy of Chinese Medical Sciences， Beijing 100700， China
2. Guang'anmen Hospital， China Academy of Chinese Medical Sciences， Beijing 100053， China
3. Academy of Integrative Medicine， Fujian University of Traditional Chinese Medicine， Fuzhou 350122， China
- Publication Type:Journal Article
- Keywords:
Hezhongxiaopi granules;
chronic atrophic gastritis;
gastric precancerous lesion;
endoplasmic reticulum stress;
apoptosis;
Nicalin （Ncln）-C/EBP homologous protein （CHOP） axis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(19):129-138
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of Hezhongxiaopi granules （HZXPG） on methylnitronitrosoguanidine （MNNG）-mediated gastric mucosal cell apoptosis and the regulatory effects on the Nicalin （Ncln）-C/EBP homologous protein （CHOP） axis and endoplasmic reticulum stress （ERS）. MethodsThe cell counting kit-8 （CCK-8） assay was employed to examine the inhibitory effect of MNNG on the proliferation of GES-1 cells， and the optimal effective dose of MNNG was selected. Human gastric mucosal GES-1 cells were allocated into the control， model （MNNG， 1.562 5 mmol·L-1）， and low/high-dose HZXPG （5% and 10% HZXPG-containing serum） groups. Phalloidin staining was employed to detect MNNG-induced morphological changes in human gastric mucosal cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was adopted to assess cell apoptosis. Annexin Ⅴ/propidium iodide （Annexin Ⅴ/PI） flow cytometry was utilized to measure the alterations in the apoptotic cycle of human gastric mucosal cells. Western blot was performed to determine the expression levels of proteins related to apoptosis， ERS， and the Ncln/CHOP axis. ResultsCompared with the control group， the model group exhibited a reduction in the surface area of GES-1 cells， endoplasmic reticulum （ER） dilation， increased early and late apoptosis rates of gastric mucosal cells， upregulated protein levels of truncated Bid （tBid）， Bcl-2-associated X protein （Bax）， cleaved-cysteinyl aspartate-specific proteinase （Caspase）-3， and cleaved-Caspase-8， and downregulated protein level of B-cell lymphoma-2 （Bcl-2） （P<0.01）. In addition， the expression levels of binding immunoglobulin protein （BiP）， Ncln， and CHOP were upregulated （P<0.01）， with enhanced Ncln expression in the ER and elevated CHOP expression in the nucleus. Compared with the model group， the high-dose HZXPG group showed a significant increase in the surface area of gastric mucosal cells. Both dose groups exhibited inhibited ER dilation and reduced early and late apoptosis rates of gastric mucosal cells （P<0.01）. Low-dose HZXPG decreased the expression of tBid and Bax （P<0.05， P<0.01） and promoted Bcl-2 expression （P<0.01）. High-dose HZXPG reduced the expression levels of tBid， Bax， cleaved-Caspase-3， and cleaved-Caspase-8 （P<0.05， P<0.01） and increased the Bcl-2 expression level （P<0.05）. Furthermore， high-dose HZXPG downregulated the expression levels of BiP， Ncln， and CHOP （P<0.05， P<0.01）， while decreasing the nuclear translocation of CHOP. ConclusionHZXPG alleviates MNNG-induced ERR-mediated apoptosis of gastric mucosal cells by inhibiting the Ncln-CHOP axis， thereby relieving gastric mucosal cell damage caused by precancerous gastric lesions.
