Geniposidic Acid Attenuates Chronic Tubulointerstitial Nephropathy Through Regulation of the NF‐ƙB/Nrf2 Pathway Via Aryl Hydrocarbon Receptor Signaling

IF 6.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Phytotherapy Research Pub Date : 2024-09-18 DOI:10.1002/ptr.8324

Yan‐Ni Wang, Xiao‐Jun Li, Wen‐Feng Wang, Liang Zou, Hua Miao, Ying‐Yong Zhao

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引用次数: 0

Abstract

Renal fibrosis is an outcome of chronic kidney disease, independent of the underlying etiology. Renal fibrosis is caused primarily by oxidative stress and inflammation. We identified the components of Plantaginis semen and elucidated their anti‐fibrotic and anti‐inflammatory mechanisms. The renoprotective components and underlying molecular mechanisms of P. semen were investigated in rats with adenine‐induced chronic tubulointerstitial nephropathy (TIN) and in idole‐3‐acetic acid (IAA)–stimulated NRK‐52E cells. Acetate and n‐butanol extracts were found to be the bioactive fractions of P. semen. A total of 65 compounds including geniposidic acid (GPA), apigenin (APG), and acteoside (ATS) were isolated and identified. Among the seven main extract components, treatment with GPA, APG, and ATS reduced the serum levels of creatinine and urea in TIN rats. Mechanistically, GPA ameliorated renal fibrosis through repressing aryl hydrocarbon receptor (AHR) signaling and regulating redox signaling including inhibiting proinflammatory nuclear factor kappa B (NF‐ƙB) and its target gene products as well as activated antioxidative nuclear factor‐erythroid‐2‐related factor 2 (Nrf2) and its downstream target gene products in both TIN rats and IAA‐stimulated NRK‐52E cells. The inhibitory effect of GPA on AHR, NF‐Ƙb, and Nrf2 signaling were partially abolished in IAA‐stimulated NRK‐52E cells treated with CH223191 compared with untreated IAA‐stimulated NRK‐52E cells. These data demonstrated that GPA alleviates oxidative stress and inflammation partly by suppressing AHR signaling.

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京尼平苷酸通过芳基烃受体信号调节 NF-ƙB/Nrf2 通路减轻慢性肾小管间质性肾病的病情

肾脏纤维化是慢性肾脏病的一种结果，与潜在病因无关。肾脏纤维化主要是由氧化应激和炎症引起的。我们确定了车前子精液的成分，并阐明了其抗纤维化和抗炎机制。我们在腺嘌呤诱导的慢性肾小管间质肾病（TIN）大鼠和吲哚-3-乙酸（IAA）刺激的 NRK-52E 细胞中研究了车前子精液的肾保护成分及其分子机制。研究发现醋酸和正丁醇提取物是精液中具有生物活性的组分。共分离并鉴定出 65 种化合物，包括玄参苷酸（GPA）、芹菜素（APG）和肌动蛋白苷（ATS）。在七种主要提取物成分中，GPA、APG 和 ATS 可降低 TIN 大鼠血清中的肌酐和尿素水平。从机理上讲，GPA通过抑制芳基烃受体（AHR）信号传导和调节氧化还原信号传导，包括抑制促炎性核因子卡巴B（NF-ƙB）及其靶基因产物，以及激活抗氧化性核因子红细胞-2相关因子2（Nrf2）及其下游靶基因产物，从而改善TIN大鼠和IAA刺激的NRK-52E细胞的肾脏纤维化。与未处理的 IAA 刺激 NRK-52E 细胞相比，用 CH223191 处理的 IAA 刺激 NRK-52E 细胞中，GPA 对 AHR、NF-Ƙb 和 Nrf2 信号转导的抑制作用被部分取消。这些数据表明，GPA 可部分通过抑制 AHR 信号来缓解氧化应激和炎症。

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来源期刊

Phytotherapy Research 医学-药学

CiteScore

12.80

自引率

5.60%

发文量

325

审稿时长

2.6 months

期刊介绍： Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.