Mechanistic insights into Qiteng Xiaozhuo Granules' regulation of autophagy for chronic glomerulonephritis treatment: Serum pharmacochemistry, network pharmacology, and experimental validation.
J Ethnopharmacol
; 324: 117819, 2024 Apr 24.
Article
en En
| MEDLINE
| ID: mdl-38286158
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Qiteng Xiaozhuo Granules (QTXZG), a traditional Chinese medicine prescription, is widely acknowledged for its therapeutic efficacy and lack of discernible toxicity in clinical practice, substantiating its potential in the treatment of chronic glomerulonephritis (CGN). Nevertheless, the specific effectiveness and underlying mechanisms of QTXZG remain insufficiently explored. AIM OF THE STUDY The purpose of this study was to explore the mechanism of the QTXZG in the treatment of CGN via targeting autophagy based on serum pharmacochemistry, network pharmacology, and experimental validation. METHODS:
Serum samples from SD rats orally administered QTXZG were analyzed using UPLC-QE/MS to identify contained compounds. Network and functional enrichment analyses elucidated QTXZG's targets and biological mechanisms. Reliability was ensured through molecular docking, in vivo and in vitro experiments.RESULTS:
After oral administration of QTXZG, 39 enriched compounds in serum samples collected 1 h later were identified as potential active agents, with 508 potential targets recognized as QTXZG-specific targets. Through integration of various databases, intersection analysis of QTXZG targets, CGN-related genes, and autophagy-related targets identified 10 core autophagy-related targets for QTXZG in CGN. GO and KEGG analyses emphasized their roles in autophagy, inflammation, and immune processes, particularly emphasizing the enrichment of the AMPK/mTOR signaling pathway. Molecular docking results demonstrated strong binding affinities between QTXZG's key compounds and the predicted core targets. In animal experiments, QTXZG was found to ameliorate renal tissue damage in CGN model mice, significantly reducing serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Importantly, both animal and cell experiments revealed QTXZG's ability to decrease excessive ROS and inflammatory factor release in mesangial cells. Furthermore, in vitro and in vivo experiments confirmed QTXZG's capacity to upregulate Beclin1 and LC3II/I expression, decrease p62 expression, and induce CGN autophagy through modulation of the AMPK/mTOR pathway.CONCLUSIONS:
This study indicated that QTXZG can induce autophagy in CGN by affecting the AMPK/mTOR pathway, and induction of autophagy may be one of the possible mechanisms of QTXZG's anti-CGN.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Medicamentos Herbarios Chinos
/
Glomerulonefritis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Ethnopharmacol
Año:
2024
Tipo del documento:
Article