Sweroside plays a role in mitigating high glucose-induced damage in human renal tubular epithelial HK-2 cells by regulating the SIRT1/NF-κB signaling pathway
Xiaodan Ma1,2, Zhixin Guo1,*, Wenhua Zhao2, and Li Chen2
1Department of Endocrinology, Second Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, 2Department of Endocrinology, Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi 046000, China
Author contributions: All authors contributed to the study conception and design. Material preparation and the experiments were performed by X.M. Data collection and analysis were performed by Z.G. and W.Z. The first draft of the manuscript was written by L.C. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Received: May 23, 2023; Revised: August 9, 2023; Accepted: August 10, 2023
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sweroside is a natural monoterpene derived from Swertia pseudochinensis Hara. Recently, studies have shown that sweroside exhibits a variety of biological activities, such as anti-inflammatory, antioxidant, and hypoglycemic effects. However, its role and mechanisms in high glucose (HG)-induced renal injury remain unclear. Herein, we established a renal injury model in vitro by inducing human renal tubular epithelial cell (HK-2 cells) injury by HG. Then, the effects of sweroside on HK-2 cell activity, inflammation, reactive oxygen species (ROS) production, and epithelial mesenchymal transition (EMT) were observed. As a result, sweroside treatment ameliorated the viability, inhibited the secretion of inflammatory cytokines (TNF-α, IL-1β, and VCAM-1), reduced the generation of ROS, and inhibited EMT in HK-2 cells. Moreover, the protein expression of SIRT1 was increased and the acetylation of p65 NF-kB was decreased in HK-2 cells with sweroside treatment. More importantly, EX527, an inhibitor of SIRT1, that inactivated SIRT1, abolished the improvement effects of sweroside on HK-2 cells. Our findings suggested that sweroside may mitigate HG-caused injury in HK-2 cells by promoting SIRT1-mediated deacetylation of p65 NF-kB.