一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Phytomedicine >>article
Phytomedicine

Phytomedicine

IF: 6.7
Download PDF

Curcumol Ameliorates Cisplatin-induced Nephrotoxicity by Targeting TAK1 and Inhibiting MAPK and NF-κB Pathways

Published:9 April 2025 DOI: 10.1016/j.phymed.2025.156752
Xuejin Jin , Miao Yuan , Lingkun Wang , Huiyan Zha , Zhiwei Zheng , Zheng Xu , Jing Shi , Guang Liang , Qian Zhou

Abstract

Background

Although cisplatin (Cis) is a foundational chemotherapeutic agent, its dose-limiting nephrotoxicity lacks clinically effective drugs. Curcumol (CUR), a bioactive sesquiterpenoid derived from Curcuma zedoariae rhizome, exhibits multi-organ protective effects. However, its therapeutic potential and molecular targets in Cis-provoked acute kidney injury (AKI) remain unexplored.

Purpose

This study systematically investigated the nephroprotection and underlying mechanism of CUR in Cis-induced nephrotoxicity.

Methods

C57BL/6 mice received intraperitoneal administration of 20 mg/kg Cis to induce AKI. Dual-concentration CUR (40/80 mg/kg) was administered pre- and post-treatment in Cis-challenged mice, with longitudinal monitoring of renal function. Human tubular epithelial cells (HK-2 cells) were used to evaluate CUR's nephroprotection in vitro. RNA-sequencing transcriptomics identified pathway-level mechanisms, while structure-based molecular docking (MOD) prioritized target proteins.

Results

CUR exhibited dose-responsive nephroprotection, reducing apoptosis, oxidative stress, and inflammation more effectively than N-acetylcysteine in pre- and post-Cis treatment regimens. Mechanistically, we revealed that nephroprotection of CUR primarily involves suppression of phosphorylation-mediated MAPK/NF-κB pathway activation, thereby mitigating the inflammatory response. Notably, MOD and Cellular thermal shift assay (CETSA) data suggested a direct interaction between CUR and TAK1. Functional validation experiments demonstrated that TAK1 silencing attenuated cisplatin-induced tubular cell injury, and TAK1 activity was essential for CUR's protective effects.

Conclusion

CUR ameliorated Cis-triggered AKI by targeting TAK1 and inhibiting MAPK and NF-κB pathways. These findings suggest that CUR may serve as a promising adjuvant to overcome the primary limitation of Cis.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Cisplatin 15663-27-1 Cl2H6N2Pt 924 suppliers $14.00-$7570.00
Cisplatin 15663-27-1 Cl2H6N2Pt 924 suppliers $14.00-$7570.00
Cisplatin 15663-27-1 Cl2H6N2Pt 924 suppliers $14.00-$7570.00
Cisplatin 15663-27-1 Cl2H6N2Pt 924 suppliers $14.00-$7570.00
Cisplatin 15663-27-1 - Inquiry
Cisplatin 15663-27-1 - Inquiry
镇坪县| 紫金县| 洛扎县| 道孚县| 井陉县| 太仆寺旗| 中牟县| 桂东县| 堆龙德庆县| 循化| 泰顺县| 鄂尔多斯市| 万安县| 明光市| 鄂尔多斯市| 永顺县| 泰兴市| 东方市| 共和县| 临泉县| 遵化市| 岳普湖县| 醴陵市| 云阳县| 石门县| 江川县| 浮山县| 繁峙县| 安国市| 黄大仙区| 乐安县| 宝清县| 清涧县| 那坡县| 新安县| 望都县| 赤壁市| 呼和浩特市| 汉源县| 滨海县| 德安县|