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.
背景:缺乏治疗肺移植缺血再灌注损伤(IRI)的有效药物仍然是一个问题。传统中药成分很有前景,但在治疗肺移植缺血再灌注损伤方面的研究很少。本研究旨在确定潜在的中药成分并阐明其作用机制:方法:采用网络药理学方法确定了十种中药成分,包括(-)-表没食子儿茶素-3-棓酸盐、槲皮素、沃戈宁、三七内酯、小檗碱、鱼腥草素、香豆素、木犀草素、金没药醇和黄芩素。对所有候选药物改善钳夹诱导的 IRI 的能力进行了测试。在LTx模型中进行了多剂量验证,重点是黄芩苷。在体外大鼠肺灌注模型中验证了黄芩苷的药理功效:结果:所有十种中药成分都能改善钳夹诱导的 IRI。多剂量验证证实黄芩苷可减轻 IRI 诱导的移植物损伤和功能障碍。黄芩素降低了IRI诱导的高级糖化终产物(AGEs)水平升高及其下游致病效应。外源性AGEs抵消了黄芩苷的治疗效果:结论:黄芩苷通过调节葡萄糖氧化而非多元醇代谢来抑制 AGE 的形成。这项研究为使用中药成分治疗LTx的IRI提供了实验室基础。
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.