Modified Huanglian Wendan Decoction improves prediabetic renal injury by activating the AMPK/ULK1 pathway to restore autophagy and suppress inflammation

作者：Zou X, Yang X, Liu X, Fan Y, Ding N, Zheng C · 发表于：International immunopharmacology · 年份：2026 · DOI：10.1016/j.intimp.2026.116966 · 研究领域：Autophagy-Related Protein-1 Homolog、Drugs, Chinese Herbal、AMP-Activated Protein Kinases、Prediabetic State、Anti-Inflammatory Agents、Animals、Autophagy、Male、Humans、Rats、Signal Transduction、Rats, Sprague-Dawley

BACKGROUND: Prediabetes represents an intermediate metabolic condition between normal blood glucose and diabetes, characterized by insulin resistance, metabolic dysfunction, and low-grade inflammation, collectively contributing to early renal injury. However, manifestations such as glomerular hyperfiltration, increased urinary protein excretion, and subclinical tubular injury are often overlooked during this stage. Therefore, elucidating the underlying molecular mechanisms and implementing early interventions may significantly attenuate subsequent renal function decline. In this context, although Modified Huanglian Wendan Decoction (MHWD) has demonstrated efficacy in regulating glucose and lipid metabolism, its effects on renal injury during prediabetes have not been fully elucidated. METHODS: UPLC-MS analysis was conducted to characterize the main active compounds of MHWD. Subsequently, a prediabetic rat model was established using a high-fat diet in combination with streptozotocin to explore the effects of MHWD on insulin sensitivity, body weight, blood glucose, and lipid profiles. Transcriptomic and proteomic analyses of the kidneys were subsequently performed to explore MHWD's molecular mechanisms, which were further validated in vivo. In vitro studies in HK-2 cells exposed to high glucose were conducted to explore MHWD mechanisms, with autophagy's role in anti-inflammatory effects assessed using chloroquine and the levels of autophagy-related proteins and inflammatory c...