Baicalein relieves lung graft ischemia-reperfusion injury by reducing advanced glycation endproducts: From screens to mechanisms.

IF 6.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Journal of Heart and Lung Transplantation Pub Date : 2025-02-13 DOI:10.1016/j.healun.2025.01.023

Dong Tian, Xiang-Yun Zheng, Sen-Lin Hou, Zeng-Wei Yu, Ye Wu, Pei-Zhi Liu, Lin-Xi Liu, Yu-Xuan Chen, Yang Zhao, Yang Li, Hong-Tao Tang, Wei-Yang Chen, Ya-Ling Liu, Chuan-Fen Zhang, Yun Wang, Hong-Ying Wen, Qiang Pu, Masaaki Sato, Lun-Xu Liu

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引用次数: 0

Abstract

Background: The lack of effective drugs for treating ischemia-reperfusion injury (IRI) in lung transplants (LTx) remains an issue. Traditional Chinese medicine (TCM) ingredients are promising but poorly studied in LTx. This study aimed to identify potential ingredients and elucidate their mechanisms.

Methods: Ten TCM ingredients, including (-)-epigallocatechin-3-gallate, quercetin, wogonin, triptolide, berberine, fisetin, coumestrol, luteolin, nobiletin, and baicalein, were identified as promising candidates using a network pharmacology approach. All the candidates were tested for their ability to improve clamp-induced IRI. Multiple-dose validation was conducted in LTx models, with a focus on baicalein. The pharmacological efficacy of baicalin was verified in an ex-vivo rat lung perfusion model.

Results: All ten TCM ingredients improved clamp-induced IRI. Multiple-dose validation confirmed that baicalein mitigated IRI-induced graft damage and dysfunction. Baicalein reduced the elevated levels of advanced glycation endproducts (AGEs) and their downstream pathogenic effects induced by IRI. Exogenous AGEs counteracted the therapeutic effect of baicalein.

Conclusions: Baicalein inhibited AGE formation by modulating glucose oxidation rather than polyol metabolism. This study provides a laboratory foundation for the use of TCM ingredients in the treatment of IRI in LTx.

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来源期刊

Journal of Heart and Lung Transplantation 医学-呼吸系统

CiteScore

10.10

自引率

6.70%

发文量

1667

审稿时长

69 days

期刊介绍： The Journal of Heart and Lung Transplantation, the official publication of the International Society for Heart and Lung Transplantation, brings readers essential scholarly and timely information in the field of cardio-pulmonary transplantation, mechanical and biological support of the failing heart, advanced lung disease (including pulmonary vascular disease) and cell replacement therapy. Importantly, the journal also serves as a medium of communication of pre-clinical sciences in all these rapidly expanding areas.