Nephroprotective effects of Amomum kravanh essential oil by inhibition of ferroptosis regulated by Nrf2/HO-1 signaling pathway

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-04-16 DOI:10.1016/j.phymed.2025.156762

Xiaoling Cheng , Wenli Hao , Silin Yu , Xvjie Gao , Liyuan Qu , Chang Liu , Yanli Wang , Yifan Sun , Jian Huang , Lu Yang , Jinhui Wang

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Abstract

Background

Amomum kravanh Pierre ex Gagnep. (BDK) is a Zingiberaceae plant traditionally widely used as a sweet fragrance, and commonly also utilized in minority medicine for various kidney diseases, especially chronic kidney disease (CKD) in Tibetan and Mongolian medicine. However, the underlying mechanisms by which it confers renal protection remain to be fully clarified.

Purpose

To investigate the renal protective mechanism of which BDK’s essential oil exerts in rats with CKD induced by adenine and 5/6 nephrectomy.

Methods

Rat models of adenine and 5/6 nephrectomy chronic nephropathy were established, and the therapeutic effects were evaluated by detecting the blood biochemical levels and H&E-/Masson staining and fiber-related factors. Then, the chemical composition of BDK’s essential oil and blood components were analyzed using GC–MS. The efficacy of eucalyptol was evaluated by adenine and 5/6 nephrectomy CKD model, with mechanistic studies conducted using RNA-seq, western blot, and metabolomic approaches.

Results

The blood biochemical levels and histopathological analyses (H&E-/Masson's staining) revealed that the BDK’s essential oil significantly enhanced renal function and ameliorated kidney tissue fibrosis. Furthermore, GC–MS analysis identified 33 components in the essential oil of BDK, with eucalyptol being the predominant chemical component at 74.07 %. Eucalyptol is capable of entering the bloodstream in its prototypical form. Then, the efficacy and mechanism of eucalyptol were confirmed by adenine/5/6 nephrectomy CKD models, and based on RNA-seq analysis, we found that eucalyptol could significantly improve kidney function and fibrosis of kidney tissues by blocking TGF-β/smad and NF-κB pathways and inhibit ferroptosis through the Nrf2/HO-1 signaling pathway.

Conclusion

Both BDK’s essential oil and its main constituent, eucalyptol, exhibited protective effects against CKD. They both ameliorated oxidative stress, inflammation, and fibrosis in adenine/5/6 nephrectomy rats. Eucalyptol is implicated in ferroptosis and regulation of renal fibrosis via the Nrf2/HO-1 pathway.

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砂仁精油通过抑制Nrf2/HO-1信号通路调控的铁下垂对肾的保护作用

damomum kravanh Pierre ex Gagnep。姜黄（BDK）是姜科植物，传统上被广泛用作甜香精，也常用于少数民族药中治疗各种肾脏疾病，特别是藏医和蒙医的慢性肾脏疾病（CKD）。然而，它赋予肾脏保护的潜在机制仍有待充分阐明。目的探讨BDK精油对腺嘌呤和5/6肾切除术所致CKD大鼠的肾保护作用机制。方法建立腺嘌呤和5/6肾切除术慢性肾病大鼠模型，通过检测血生化水平、H&；E-/Masson染色及纤维相关因子评价治疗效果。采用气相色谱-质谱联用技术，对其挥发油和血液成分进行化学成分分析。桉树精油的疗效通过腺嘌呤和5/6肾切除CKD模型进行评估，并使用RNA-seq、western blot和代谢组学方法进行机制研究。结果血生化水平及组织病理学分析（H&；E-/Masson染色）显示，大鼠丹参精油能明显增强肾功能，改善肾组织纤维化。此外，GC-MS分析鉴定出BDK精油中的33种成分，其中桉叶精油为主要化学成分，占74.07%。桉树精油能够以其原型形式进入血液。随后，我们通过腺嘌呤/5/6肾切除CKD模型证实了桉树精油的功效和作用机制，并通过RNA-seq分析发现，桉树精油可通过阻断TGF-β/smad和NF-κB通路，通过Nrf2/HO-1信号通路抑制铁上沉，从而显著改善肾功能和肾脏组织纤维化。结论桉树精油及其主要成分桉树醇对慢性肾病均有保护作用。它们都能改善腺嘌呤/5/6肾切除术大鼠的氧化应激、炎症和纤维化。桉树醇通过Nrf2/HO-1途径参与铁下垂和肾纤维化的调节。

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

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.