Asiaticoside improves diabetic nephropathy by reducing inflammation, oxidative stress, and fibrosis: An in vitro and in vivo study.

IF 4.2 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

World Journal of Diabetes Pub Date : 2024-10-15 DOI:10.4239/wjd.v15.i10.2111

Lan-Gen Zhuang, Rong Zhang, Guo-Xi Jin, Xiao-Yan Pei, Qiong Wang, Xiao-Xu Ge

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引用次数: 0

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.

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积雪草苷通过减少炎症、氧化应激和纤维化改善糖尿病肾病：一项体外和体内研究。

背景：糖尿病肾病（DN）是糖尿病的一种严重微血管并发症，以炎症、氧化应激和肾纤维化为特征。积雪草苷（AC）具有抗炎、抗氧化和抗纤维化的特性，对糖尿病肾病具有潜在的治疗作用。本研究旨在探讨AC对DN的保护作用，并阐明涉及核因子红细胞2相关因子2（NRF2）/血红素加氧酶-1（HO-1）抗氧化途径的潜在机制：方法：在体外大鼠肾小球系膜细胞（HBZY-1）中评估 AC 对高葡萄糖（HG）诱导的增殖、炎症、氧化应激和纤维化的影响。建立了链脲佐菌素诱导的 DN 大鼠模型，以评估 AC 在体内对肾损伤、炎症、氧化应激和纤维化的影响。通过在细胞模型中进行药理抑制研究，考察了 NRF2/HO-1 通路的参与情况：结果：AC 可抑制 HG 诱导的 HBZY-1 细胞增殖，并显著改善大鼠 DN 的各种指标，包括体重减轻、血糖、血清肌酐、血尿素氮和 24 小时尿蛋白升高。体外和体内研究表明，AC 通过降低白细胞介素（IL）-6、IL-8、肿瘤坏死因子-α、活性氧和丙二醛水平，同时提高超氧化物歧化酶活性，从而减少炎症和氧化应激。此外，AC 还能抑制胶原蛋白 I、胶原蛋白 IV 和纤连蛋白等纤维化标记物的表达。AC 激活了细胞核中 NRF2 的表达，并增加了肾组织和 HG 诱导的 HBZY-1 细胞中 HO-1 和 NAD(P)H 脱氢酶（醌）1 蛋白的表达：AC通过激活NRF2/HO-1信号通路，减轻炎症、氧化应激和纤维化，从而改善DN。这些发现不仅凸显了 AC 是一种治疗 DN 的有前途的候选药物，而且还强调了靶向 NRF2/HO-1 通路在开发治疗以氧化应激和炎症为特征的其他慢性肾脏疾病的新型疗法方面的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Diabetes ENDOCRINOLOGY & METABOLISM-

自引率

2.40%

发文量

909

期刊介绍： The WJD is a high-quality, peer reviewed, open-access journal. The primary task of WJD is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of diabetes. In order to promote productive academic communication, the peer review process for the WJD is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJD are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in diabetes. Scope: Diabetes Complications, Experimental Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetes, Gestational, Diabetic Angiopathies, Diabetic Cardiomyopathies, Diabetic Coma, Diabetic Ketoacidosis, Diabetic Nephropathies, Diabetic Neuropathies, Donohue Syndrome, Fetal Macrosomia, and Prediabetic State.