Ellagic acid inhibits high glucose‑induced injury in rat mesangial cells via the PI3K/Akt/FOXO3a signaling pathway

Lin,Wei; Liu,Guojian; Kang,Xiaowen; Guo,Ping; Shang,Yu; Du,Ruomei; Wang,Xiyue; Chen,Liting; Yue,Rui; Kong,Fanwu; Zhu,Qihan

doi:10.3892/etm.2021.10449

Ellagic acid inhibits high glucose‑induced injury in rat mesangial cells via the PI3K/Akt/FOXO3a signaling pathway

Authors:
- Wei Lin
- Guojian Liu
- Xiaowen Kang
- Ping Guo
- Yu Shang
- Ruomei Du
- Xiyue Wang
- Liting Chen
- Rui Yue
- Fanwu Kong
- Qihan Zhu
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Affiliations: Department of General Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Respiration, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Laboratory Department, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, Heilongjiang 150036, P.R. China, Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: July 15, 2021 https://doi.org/10.3892/etm.2021.10449
Article Number: 1017
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The pathological damage of mesangial cells serves an important role in the occurrence and development of diabetic nephropathy. Ellagic acid has been reported to possess antioxidant, antitumor, antiviral and anti‑inflammatory properties in several diseases, but the roles of ellagic acid in diabetic nephropathy are unclear. The main aim of the present study was to investigate the effect of ellagic acid on high glucose‑induced mesangial cell damage. The results revealed that high glucose could induce the hyperproliferation of mesangial cells, decrease the activity of superoxide dismutase, increase the malondialdehyde content, the level of reactive oxygen species, the secretion of inflammatory factors (TNF‑α, IL‑1β and IL‑6) and the synthesis of extracellular matrix (Fibronectin, MMP‑9 and TIMP‑1) and activate the PI3K/Akt/FOXO3a signaling pathway. Ellagic acid could attenuate the injury of mesangial cells induced by high glucose in a concentration‑dependent manner and its effect was consistent with that of a PI3K inhibitor (LY294002). Moreover, a PI3K agonist (740Y‑P) reversed the protective effect of ellagic acid on mesangial cells induced by high glucose. In conclusion, ellagic acid protected mesangial cells from high glucose‑induced injury in a concentration‑dependent manner. The mechanism may be associated with ellagic acid inhibiting the activation of the PI3K/Akt signaling pathway and reducing the expression levels of downstream transcription factor FOXO3a.

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