Mechanisms of Xuefu Zhuyu decoction in treating diabetic kidney disease-induced renal fibrosis: UPLC-Q/TOF-MS, network pharmacology, and experimental validation

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Yifei Zhang Shuaixing Zhang Zeyu Zhang Zijing Cao Xuehui Bai Shujiao Zhang Mengqi Zhou Jingyi Tang Yiran Xie Weijing Liu Yuning Liu
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제5호, 571~597쪽, 전체 27쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.09.01

국문 초록

Xuefu Zhuyu decoction (XFZY) has therapeutic effects on diabetic kidney disease (DKD)-induced renal interstitial fibrosis (RIF), but the mechanisms are unclear. This study investigates XFZY's molecular mechanisms through network pharmacology and experimental validation. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and database screening was used to identify XFZY bioactive compounds. Common targets between these compounds and DKD-induced RIF were analyzed. A protein-protein interaction network was constructed, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Molecular docking validated interactions between XFZY compounds and targets. In vivo, a mouse model of DKD-induced RIF was established using streptozotocin and a high-fat diet. In vitro, human kidney-2 cells were treated with advanced glycation end products. Renal function and pathology were assessed, along with key protein expression levels. Using UPLC-Q-TOF-MS technology and database screening, seven bioactive components of XFZY were identified. Network pharmacology identified 61 common targets, including core targets like AKT1, MTOR, ULK1, and MMP9. Enrichment analysis indicated the AMPK signaling pathway is closely related to XFZY's therapeutic effects on DKD-induced RIF. Molecular docking demonstrated the seven bioactive components exhibited high binding affinities with key targets in the AMPK pathway (AMPK, mTOR, ULK1). In vivo, XFZY improved renal function, ameliorated renal pathology, reduced tubular injury, and alleviated RIF. Both in vivo and in vitro, XFZY increased phosphorylated AMPK and phosphorylated ULK1 expression, decreased phosphorylated MTOR, and reduced LC3 and p62 expression in the autophagy pathway. XFZY may alleviate DKD-induced RIF by modulating autophagy via the AMPK/MTOR/ULK1 pathway.

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키워드

AMPK signaling pathway Autophagy Diabetic kidney disease Network pharmacology Kidney tubulointerstitial fibrosis Xuefu Zhuyu decoction