---
title: "Modified Huanglian Wendan Decoction protects prediabetic kidneys via AMPK/ULK1‑mediated autophagy"
id: "pubmed-42259235"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42259235"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42259235/"
doi: "10.1016/j.intimp.2026.116966"
published_at: "2026-09-15T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Modified Huanglian Wendan Decoction protects prediabetic kidneys via AMPK/ULK1‑mediated autophagy
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42259235
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42259235/)
- **DOI:** [10.1016/j.intimp.2026.116966](https://doi.org/10.1016%2Fj.intimp.2026.116966)
- **Published At:** 2026-09-15T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study evaluated **Modified Huanglian Wendan Decoction (MHWD)** for renal protection in prediabetes, focusing on autophagy and inflammation pathways. - UPLC‑MS identified 15 principal chemical constituents of MHWD. - A prediabetic rat model was established using a high‑fat diet combined with streptozotocin (STZ) to induce metabolic changes and early renal injury. - MHWD treatment improved metabolic parameters in prediabetic rats, including reductions in hyperglycemia, insulin resistance, dyslipidemia, and weight gain. - MHWD attenuated renal injury and reduced systemic and renal inflammatory markers in treated animals. - Transcriptomic and proteomic analyses of kidney tissue implicated metabolic regulation, autophagy restoration, and anti‑inflammatory effects as core MHWD mechanisms. - Transmission electron microscopy, immunofluorescence, and Western blot confirmed that MHWD restored renal **autophagy** and suppressed inflammation through activation of the **AMPK/ULK1** pathway. - In vitro, MHWD recapitulated protective effects in HK‑2 renal tubular cells exposed to high glucose, showing restored autophagy and lowered inflammatory cytokine levels. - Metformin, an AMPK activator, produced comparable effects and was used as a positive control. - Inhibition experiments using chloroquine (autophagy inhibitor) and Compound C (AMPK inhibitor) blocked MHWD’s protective effects, indicating dependence on **AMPK/ULK1‑dependent autophagy**. - The authors conclude MHWD alleviates metabolic dysfunction and preserves renal function in prediabetes by restoring autophagic homeostasis, enhancing energy metabolism, and suppressing inflammation, providing a mechanistic basis for early kidney protection and potential clinical application.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jun 8. # Modified Huanglian Wendan Decoction improves prediabetic renal injury by activating the AMPK/ULK1 pathway to restore autophagy and suppress inflammation [Xiuqi Zou](https://pubmed.ncbi.nlm.nih.gov/?term=Zou+X&cauthor_id=42259235)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#full-view-affiliation-1 "Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China; Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China."), [Xing Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+X&cauthor_id=42259235)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#full-view-affiliation-2 "Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China."), [Xinbang Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+X&cauthor_id=42259235)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#full-view-affiliation-3 "Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China."), [Yanbo Fan](https://pubmed.ncbi.nlm.nih.gov/?term=Fan+Y&cauthor_id=42259235)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#full-view-affiliation-2 "Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China."), [Nian Ding](https://pubmed.ncbi.nlm.nih.gov/?term=Ding+N&cauthor_id=42259235)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#full-view-affiliation-4 "Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China. Electronic address: 1468153352@qq.com."), [Chenghong Zheng](https://pubmed.ncbi.nlm.nih.gov/?term=Zheng+C&cauthor_id=42259235)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#full-view-affiliation-5 "Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China. Electronic address: chzheng28@126.com.") Affiliations Expand ### Affiliations * 1 Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China; Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China. * 2 Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China. * 3 Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China. * 4 Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China. Electronic address: 1468153352@qq.com. * 5 Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China. Electronic address: chzheng28@126.com. * PMID: **42259235** * DOI: [ 10.1016/j.intimp.2026.116966 ](https://doi.org/10.1016/j.intimp.2026.116966) Item in Clipboard # Modified Huanglian Wendan Decoction improves prediabetic renal injury by activating the AMPK/ULK1 pathway to restore autophagy and suppress inflammation Xiuqi Zou et al. Int Immunopharmacol. 2026. Show details Display options Display options Format Abstract PubMed PMID Int Immunopharmacol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+Immunopharmacol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+Immunopharmacol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42259235/) . 2026 Sep 15:185:116966. doi: 10.1016/j.intimp.2026.116966. Epub 2026 Jun 8. ### Authors [Xiuqi Zou](https://pubmed.ncbi.nlm.nih.gov/?term=Zou+X&cauthor_id=42259235)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#short-view-affiliation-1 "Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China; Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China."), [Xing Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+X&cauthor_id=42259235)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#short-view-affiliation-2 "Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China."), [Xinbang Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+X&cauthor_id=42259235)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#short-view-affiliation-3 "Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China."), [Yanbo Fan](https://pubmed.ncbi.nlm.nih.gov/?term=Fan+Y&cauthor_id=42259235)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#short-view-affiliation-2 "Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China."), [Nian Ding](https://pubmed.ncbi.nlm.nih.gov/?term=Ding+N&cauthor_id=42259235)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#short-view-affiliation-4 "Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China. Electronic address: 1468153352@qq.com."), [Chenghong Zheng](https://pubmed.ncbi.nlm.nih.gov/?term=Zheng+C&cauthor_id=42259235)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42259235/#short-view-affiliation-5 "Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China. Electronic address: chzheng28@126.com.") ### Affiliations * 1 Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China; Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China. * 2 Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China. * 3 Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China. * 4 Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China. Electronic address: 1468153352@qq.com. * 5 Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China. Electronic address: chzheng28@126.com. * PMID: **42259235** * DOI: [ 10.1016/j.intimp.2026.116966 ](https://doi.org/10.1016/j.intimp.2026.116966) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **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 cytokines determined. Metformin, an AMPK activator, was used as a positive control to assess MHWD's effects on the AMPK/ULK1 pathway, autophagy, and inflammatory responses. The AMPK inhibitor Compound C was subsequently applied to assess whether these protective effects were dependent on the AMPK/ULK1 pathway. **Results:** UPLC-MS analysis identified 15 principal chemical constituents of MHWD. In prediabetic rats, MHWD treatment alleviated metabolic abnormalities, including hyperglycemia, insulin resistance, dyslipidemia, and weight gain, while attenuating renal injury and systemic as well as renal inflammation. Transcriptomic and proteomic analyses indicated that MHWD exerted its core effects through metabolic regulation, restoration of autophagy, and anti-inflammatory actions. Transmission electron microscopy, immunofluorescence, and Western blot analyses confirmed that MHWD restores renal autophagy and suppresses inflammation via the AMPK/ULK1 pathway. These effects were recapitulated in high-glucose-exposed HK-2 cells and were comparable to those of metformin. Inhibition by chloroquine or Compound C suppressed the protective effects of MHWD, indicating that its renal protective and anti-inflammatory benefits were mediated via AMPK/ULK1-dependent autophagy, thereby mitigating metabolic dysregulation and renal injury in prediabetic states. **Conclusions:** MHWD ameliorates metabolic disorders and preserves renal function in prediabetes by restoring autophagic homeostasis, enhancing energy metabolism, and suppressing inflammation via the AMPK/ULK1 pathway, offering a mechanistic basis for early kidney protection and potential clinical application. **Keywords:** AMPK/ULK1 signalling; Autophagy; Inflammation; Modified Huanglian Wendan Decoction; Prediabetes. Copyright © 2024. Published by Elsevier B.V. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Mechanism of Huanglian Wendan Decoction in ameliorating non-alcoholic fatty liver disease via modulating gut microbiota-mediated metabolic reprogramming and activating the LKB1/AMPK pathway. ](https://pubmed.ncbi.nlm.nih.gov/40892742/) Zhu J, Chen Y, Han Y, Li J.Zhu J, et al.PLoS One. 2025 Sep 2;20(9):e0331303. doi: 10.1371/journal.pone.0331303. eCollection 2025.PLoS One. 2025.PMID: 40892742Free PMC article. * [ Huanglian wendan decoction attenuates hepatic inflammation and lipogenesis via inhibition of the NF-κB/HDAC1/SREBP-1c axis. ](https://pubmed.ncbi.nlm.nih.gov/42276391/) Fan W, Zhou F, Song Q, Liu L, Huang S, Pan J, Zhang Y, Yang Q, Pan M, Zhang Y.Fan W, et al.J Ethnopharmacol. 2026 Nov 15;370:121984. doi: 10.1016/j.jep.2026.121984. Epub 2026 Jun 11.J Ethnopharmacol. 2026.PMID: 42276391 * [ Isoliquiritigenin attenuates myocardial ischemia reperfusion through autophagy activation mediated by AMPK/mTOR/ULK1 signaling. ](https://pubmed.ncbi.nlm.nih.gov/39123142/) Shen L, Zhu Y, Chen Z, Shen F, Yu W, Zhang L.Shen L, et al.BMC Cardiovasc Disord. 2024 Aug 9;24(1):415. doi: 10.1186/s12872-024-04054-z.BMC Cardiovasc Disord. 2024.PMID: 39123142Free PMC article. * [ Dietary glycation compounds - implications for human health. ](https://pubmed.ncbi.nlm.nih.gov/39150724/) Hellwig M, Diel P, Eisenbrand G, Grune T, Guth S, Henle T, Humpf HU, Joost HG, Marko D, Raupbach J, Roth A, Vieths S, Mally A.Hellwig M, et al.Crit Rev Toxicol. 2024 Sep;54(8):485-617. doi: 10.1080/10408444.2024.2362985. Epub 2024 Aug 16.Crit Rev Toxicol. 2024.PMID: 39150724 * [ Gegen Qinlian decoction ameliorates insulin resistance in type 2 diabetes: A systematic review and meta-analysis of RCTs with mechanistic insights into SIRT1/AMPK pathway activation. ](https://pubmed.ncbi.nlm.nih.gov/41297722/) Liao Y, Yang L, Tang S, Yue R.Liao Y, et al.J Ethnopharmacol. 2026 Mar 1;358:120960. doi: 10.1016/j.jep.2025.120960. Epub 2025 Nov 24.J Ethnopharmacol. 2026.PMID: 41297722 [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42259235) ## MeSH terms * AMP-Activated Protein Kinases* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22AMP-Activated+Protein+Kinases%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=AMP-Activated+Protein+Kinases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42259235/) * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncb
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