Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 15, 2024; 15(10): 2111-2122
Published online Oct 15, 2024. doi: 10.4239/wjd.v15.i10.2111
Asiaticoside improves diabetic nephropathy by reducing inflammation, oxidative stress, and fibrosis: An in vitro and in vivo study
Lan-Gen Zhuang, Rong Zhang, Guo-Xi Jin, Xiao-Yan Pei, Qiong Wang, Xiao-Xu Ge
Lan-Gen Zhuang, Guo-Xi Jin, Xiao-Yan Pei, Qiong Wang, Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, Anhui Province, China
Rong Zhang, Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Xiao-Xu Ge, Department of Endocrinology, Tongren Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200336, China
Author contributions: Zhuang LG and Ge XX participated in literature search, study design, and manuscript writing and critical revision; Zhang R, Jin GX, Pei XY, and Wang Q participated in data collection, analysis, and interpretation; and all authors read and approved the final manuscript.
Supported by the General Project of Anhui Provincial Health and Construction Commission, No. AHWJ2022b056.
Institutional animal care and use committee statement: This animal study was reviewed and approved by the Ethics Committee of Bengbu Medical College (approval No. 2022-117).
Conflict-of-interest statement: Lan-Gen Zhuang has received research funding from the Natural Science Research Project of Anhui Educational Committee and the General project of Anhui Provincial Health and Construction Commission. Other authors declare that there are no conflicts of interest to disclose for this article.
Data sharing statement: The datasets used or/and analyzed during the current study are available from the corresponding author upon email request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Xu Ge, MD, Doctor, Department of Endocrinology, Tongren Hospital Affiliated to Shanghai Jiao Tong University, No. 1111 Xianxia Road, Changning District, Shanghai 200336, China. uyhyt41964@163.com
Received: March 7, 2024
Revised: May 30, 2024
Accepted: July 22, 2024
Published online: October 15, 2024
Processing time: 202 Days and 20.2 Hours
Abstract
BACKGROUND

Diabetic nephropathy (DN) is a severe microvascular complication of diabetes characterized by inflammation, oxidative stress, and renal fibrosis. Asiaticoside (AC) exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties, suggesting potential therapeutic benefits for DN. This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) antioxidant pathway.

AIM

To investigate the renoprotective effects of AC against DN and elucidate the role of the NRF2/HO-1 pathway.

METHODS

The effects of AC on high glucose (HG)-induced proliferation, inflammation, oxidative stress, and fibrosis were evaluated in rat glomerular mesangial cells (HBZY-1) in vitro. A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury, inflammation, oxidative stress, and fibrosis. The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model.

RESULTS

AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats, including reduced body weight, and elevated blood glucose, serum creatinine, blood urea nitrogen, and 24-h urine protein. Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, reactive oxygen species, and malondialdehyde levels while increasing superoxide dismutase activity. Additionally, AC suppressed the expression of fibrogenic markers such as collagen I, collagen IV, and fibronectin. AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase (Quinone) 1 protein expression in renal tissues and HG-induced HBZY-1 cells.

CONCLUSION

AC improves DN by reducing inflammation, oxidative stress, and fibrosis through the activation of the NRF2/HO-1 signaling pathway. These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation.

Keywords: Asiaticoside; Diabetic nephropathy; Inflammation; Renal fibrosis; Reactive oxygen species

Core Tip: This study investigated the protective effects of asiaticoside (AC) in diabetic nephropathy (DN) using in vitro and in vivo models. AC attenuated high glucose-induced proliferation, inflammation, oxidative stress, and fibrosis in rat glomerular mesangial cells. In a streptozotocin-induced DN rat model, AC ameliorated renal injury, and reduced inflammatory cytokines, oxidative stress markers, and fibrogenic markers. Notably, the renoprotective effects of AC were associated with the activation of the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 antioxidant signaling pathway, suggesting AC’s therapeutic potential for DN by targeting inflammation, oxidative stress, and fibrosis through NRF2-associated mechanisms.