Huaier Attenuates Renal Injury in Type 2 Diabetic Nephropathy by Ameliorating Mitochondrial Dysfunction and Inhibiting Tubular Epithelial Cell Apoptosis.
- 1Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin Province, China.
- 2Clinical Research Department, The Second Hospital of Jilin University, Changchun, Jilin Province, China.
- 3Center for Pharmacodynamics and Toxicology Evaluation, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin Province, China.
Abstract
Background
Diabetic nephropathy (DN) is a major microvascular complication of Type 2 diabetes, with renal tubular epithelial cells (RTECs) apoptosis playing a pivotal role in its progression. The aqueous extract of Trametes robiniophila Murr. (Huaier) has shown renoprotective effects, but its specific molecular mechanisms in DN remain to be fully elucidated.Objective
This study aimed to investigate the therapeutic effects of Huaier aqueous extract on DN and verify whether its anti-apoptotic mechanism is mediated through the Wnt/β-catenin pathway using the pathway activator SKL2001.Methods
In vivo, KKAy Type 2 diabetic mice were treated with Huaier (5 g/kg/day) for 12 weeks to evaluate renal function and histopathology. In vitro, HK-2 cells were treated with high glucose and palmitate (HG + PA) to induce injury. The Wnt/β-catenin pathway activator SKL2001 was employed to determine if activating this pathway could abolish the protective effects of Huaier.Results
Bioinformatics analysis indicates that the regulation of apoptosis is the primary mechanism by which Huaier improves DN. In vivo, Huaier reduced UACR and improved renal histopathology in KKAy mice. Consistently, TUNEL staining and molecular analysis confirmed that Huaier significantly suppressed RTECs apoptosis within the renal tissues. In vitro experiments demonstrated that Huaier significantly inhibited HG + PA-induced oxidative stress, mitochondrial dysfunction, and RTECs apoptosis. Notably, the administration of SKL2001 effectively reversed these protective effects, leading to increased β-catenin expression and elevated apoptosis levels despite Huaier treatment.Conclusion
Huaier aqueous extract mitigates RTECs apoptosis and renal injury in Type 2 diabetic nephropathy by suppressing the Wnt5a/β-catenin signaling pathway.
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BibTeX
@article{guan2026huaier,
title = {{Huaier Attenuates Renal Injury in Type 2 Diabetic Nephropathy by Ameliorating Mitochondrial Dysfunction and Inhibiting Tubular Epithelial Cell Apoptosis.}},
author = {Yucan Guan and Xiaoying Bai and Xianping Wei and Tao Ding and Ping Luo and Ping Nie},
journal = {Journal of diabetes},
year = {2026},
month = oct,
doi = {10.1111/1753-0407.70290},
url = {https://europepmc.org/article/MED/42957591},
note = {CC BY},
}
RIS
TY - JOUR
TI - Huaier Attenuates Renal Injury in Type 2 Diabetic Nephropathy by Ameliorating Mitochondrial Dysfunction and Inhibiting Tubular Epithelial Cell Apoptosis.
AU - Yucan Guan
AU - Xiaoying Bai
AU - Xianping Wei
AU - Tao Ding
AU - Ping Luo
AU - Ping Nie
PY - 2026
DA - 2026/10/29
JO - Journal of diabetes
DO - 10.1111/1753-0407.70290
UR - https://europepmc.org/article/MED/42957591
AB - Background Diabetic nephropathy (DN) is a major microvascular complication of Type 2 diabetes, with renal tubular epithelial cells (RTECs) apoptosis playing a pivotal role in its progression. The aqueous extract of Trametes robiniophila Murr. (Huaier) has shown renoprotective effects, but its specific molecular mechanisms in DN remain to be fully elucidated.Objective This study aimed to investigate the therapeutic effects of Huaier aqueous extract on DN and verify whether its anti-apoptotic mechanism is mediated through the Wnt/β-catenin pathway using the pathway activator SKL2001.Methods In vivo, KKAy Type 2 diabetic mice were treated with Huaier (5 g/kg/day) for 12 weeks to evaluate renal function and histopathology. In vitro, HK-2 cells were treated with high glucose and palmitate (HG + PA) to induce injury. The Wnt/β-catenin pathway activator SKL2001 was employed to determine if activating this pathway could abolish the protective effects of Huaier.Results Bioinformatics analysis indicates that the regulation of apoptosis is the primary mechanism by which Huaier improves DN. In vivo, Huaier reduced UACR and improved renal histopathology in KKAy mice. Consistently, TUNEL staining and molecular analysis confirmed that Huaier significantly suppressed RTECs apoptosis within the renal tissues. In vitro experiments demonstrated that Huaier significantly inhibited HG + PA-induced oxidative stress, mitochondrial dysfunction, and RTECs apoptosis. Notably, the administration of SKL2001 effectively reversed these protective effects, leading to increased β-catenin expression and elevated apoptosis levels despite Huaier treatment.Conclusion Huaier aqueous extract mitigates RTECs apoptosis and renal injury in Type 2 diabetic nephropathy by suppressing the Wnt5a/β-catenin signaling pathway.
SN - 1753-0393
SN - 1753-0407
ER -