Mechanisms of Core Compound Formula and Compatibility of Traditional Chinese Medicine Components for Prevention and Treatment of Chronic Atrophic Gastritis Based on Huazhuo Jiedu Therapy
10.13422/j.cnki.syfjx.20260835
- VernacularTitle:化浊解毒法防治慢性萎缩性胃炎的核心复方作用机制及中药组分配伍研究
- Author:
Fan GAO
1
;
Xiaoxuan MO
1
;
Fengyue XU
1
;
Jiaye TIAN
1
;
Xinmeng ZHAO
1
;
Jianming JIANG
1
;
Qiuhong GUO
1
Author Information
1. Hebei University of Chinese Medicine， Shijiazhuang 050200， China
- Publication Type:Journal Article
- Keywords:
chronic atrophic gastritis;
Huazhuo Jiedu therapy;
uniform design;
connexin 43 （CX43）;
Wnt/β-catenin pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(21):51-64
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo reveal the compatibility rules of the core compound formula and traditional Chinese medicine （TCM） components for prevention and treatment of chronic atrophic gastritis （CAG） by Huazhuo Jiedu （turbidity-resolving and detoxifying） therapy through uniform design in view of the potential regulatory pathway of endogenous turbid-toxin retention in CAG， elucidate the potential pathway by which the compound formulas regulate the Wnt/β-catenin-connexin 43 （CX43） signaling axis， demonstrated the efficacy enhancement and toxicity attenuation among the components， thus providing experimental evidence for the scientific application of multi-component， multi-target compatibility in TCM compound formulas. MethodsA mouse model of CAG was established with N-methyl-N-nitrosourea （MNU）. Sixty mice were randomly allocated into 5 groups （n=12 per group）： blank control， model， low-dose Huazhuo Jiedu core compound formula （HXFF-L， 4.004 g·kg-1）， high-dose Huazhuo Jiedu core compound formula （HXFF-H， 8.008 g·kg-1）， and positive control （folic acid at 11 mg·kg-1 + vitamin B12 at 14 mg·kg-1）. The therapeutic efficacy and molecular mechanism of the core compound formula were evaluated by hematoxylin-eosin （HE） staining， Alcian blue-periodic acid-Schiff （AB-PAS） staining， enzyme-linked immunosorbent assay （ELISA）， transmission electron microscopy （TEM）， immunofluorescence assay， and Western blot. The chemical components of the core compound formula were detected and effective components were screened by ultra-high performance liquid chromatography coupled with quadrupole-orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS）. Another 120 mice were randomized into blank control， model， and 8 HXFF component-combination groups with different dosages （uniform design groups 1-8， n=12 per group）. A uniform design was adopted， with pathological scores of mouse gastric tissue as well as serum levels of pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， and gastrin 17 （GAS17） set as dependent variables. Multivariate linear regression analysis was performed to predict the optimal proportion of core components in the compound formula and explore its compatibility rules. ResultsPharmacodynamic validation showed that compared with the blank control group， the model group had decreased gastric weight index （P<0.01） and increased pathological damage score and inflammatory factor levels （P<0.01）. Compared with the model group， these indicators were reversed in the HXFF-L， HXFF-H， and positive control groups （P<0.05， P<0.01）. Immunofluorescence results showed that CX43 expression was downregulated in the model group compared with the blank control group （P<0.01） and upregulated in the HXFF-H and positive control groups compared with the model group （P<0.05， P<0.01）. Western blot results showed that compared with the blank control group， the model group demonstrated upregulated protein levels of Wnt and β-catenin in the gastric tissue （P<0.01）. Compared with those in the model group， the protein level of Wnt was downregulated in the HXFF-L， HXFF-H， and positive control groups （P<0.05， P<0.01）， while that of β-catenin was downregulated only in the HXFF-H group （P<0.05）. A total of 25 compounds were identified in the core compound formula， including 9 from Coptidis Rhizoma， 10 from Pogostemonis Herba， 2 from Scorpio， and 4 from Lilii Bulbus. According to the category and origin of compounds， Coptidis Rhizoma alkaloids， Pogostemonis Herba volatile oils， Scorpio peptides， and Lilii Bulbus alkaloids were finally selected for component research. The predicted optimal combination of TCM components was as follows： Coptidis Rhizoma alkaloids at 75 mg·kg-1， Pogostemonis Herba volatile oils at 2.25 mg·kg-1， Scorpio protein extract at 90 mg·kg-1， and Lilii Bulbus alkaloids at 9 mg·kg-1. Coptidis Rhizoma alkaloids， Scorpio protein extract， Pogostemonis Herba volatile oils， and Lilii Bulbus alkaloids can ameliorate pathological lesions of the gastric tissue. Scorpio protein extract exerted positive regulatory effects on the gastric function， while Pogostemonis Herba volatile oils and Lilii Bulbus alkaloids showed negative correlations with partial gastric function indicators. Further investigations are required to clarify their dose-effect relationships and safety profiles. ConclusionThis study， for the first time， predicts the optimal proportion and synergistic regulatory mechanism of the core compound formula of Huazhuo Jiedu therapy， revealing the synergistic compatibility logic of its components. It provides a novel strategy for the precise TCM treatment of CAG and the modern development of compound formulas.
