Vascular Biology lab, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, India.
Vascular Biology lab, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, India; School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur, 613401, Tamil Nadu, India.
Phytomedicine. 2022 Jul;101:154123. doi: 10.1016/j.phymed.2022.154123. Epub 2022 Apr 26.
The primary therapeutic strategy in managing ischemic heart diseases is to restore the perfusion of the myocardial ischemic area by surgical methods that often result in an unavoidable injury called ischemia-reperfusion injury (IR). Fisetin is an effective flavonoid with antioxidant and anti-inflammatory properties, proven to be cardioprotective against IR injury in both in-vitro and invivo models, apart from its promising health benefits against cancer, diabetes, and neurodegenerative ailments.
The potential of fisetin in attenuating myocardial IR is inconclusive as the effectiveness of fisetin needs more understanding in terms of its possible target sites and underlying different mechanisms. Considering the surge in recent scientific interests in fisetin as a pharmacological agent, this review not only updates the existing preclinical and clinical studies with fisetin and its underlying mechanisms but also summarizes its possible targets during IR protection.
We performed a literature survey using search engines Pubmed, PMC, Science direct, Google, and research gate published across the years 2006-2021. The relevant studies were extracted from the databases with the combinations of the following keywords and summarized: myocardial ischemia-reperfusion injury, natural products, flavonoid, fisetin, PI3K, JAK-STAT, Nrf2, PKC, JNK, autophagy.
Fisetin is reported to be effective in attenuating IR injury by delaying the clotting time, preserving the mitochondrial function, reducing oxidative stress, and inhibiting GSK 3β. But it failed to protect diseased cardiomyocytes challenged to IR. As discussed in the current review, fisetin not only acts as a conventional antioxidant and anti-inflammatory agent to exert its biological effect but may also exert modulatory action on the cellular metabolism and adaptation via direct action on various signalling pathways that comprise PI3K, JAK-STAT, Nrf2, PKC, JNK, and autophagy. Moreover, the dosage of fisetin and co-morbidities like diabetes and obesity are found to be detrimental factors for cardioprotection.
For further evaluation and smooth clinical translation of the fisetin molecule in IR treatment, researchers should pay close attention to the potential of fisetin to possibly alter the key cardioprotective pathways and dosage, as the efficacy of fisetin is tissue and cell type-specific and varies with different doses.
在治疗缺血性心脏病时，主要的治疗策略是通过手术方法恢复心肌缺血区域的灌注，而这种方法常常导致不可避免的损伤，即缺血再灌注损伤（IR）。漆黄素是一种有效的黄酮类化合物，具有抗氧化和抗炎特性，已被证明在体外和体内模型中对 IR 损伤具有心脏保护作用，除了对癌症、糖尿病和神经退行性疾病有很好的健康益处外。
漆黄素减轻心肌 IR 的潜力尚不确定，因为需要更多地了解漆黄素在其可能的靶位和潜在的不同机制方面的有效性。考虑到最近科学界对漆黄素作为一种药理学药物的兴趣激增，本综述不仅更新了现有的关于漆黄素及其潜在机制的临床前和临床研究，还总结了其在 IR 保护期间的可能靶位。
我们使用 Pubmed、PMC、Science direct、Google 和 research gate 等搜索引擎进行了文献调查，这些搜索引擎涵盖了 2006 年至 2021 年出版的文献。从数据库中提取相关研究，使用以下关键词组合进行检索，并进行了总结：心肌缺血再灌注损伤、天然产物、黄酮类化合物、漆黄素、PI3K、JAK-STAT、Nrf2、PKC、JNK、自噬。
研究表明，漆黄素通过延迟凝血时间、保护线粒体功能、减少氧化应激和抑制 GSK 3β，可有效减轻 IR 损伤。但它未能保护受到 IR 挑战的病变心肌细胞。正如本综述中所讨论的，漆黄素不仅作为一种传统的抗氧化剂和抗炎剂发挥其生物学作用，而且还可能通过直接作用于包括 PI3K、JAK-STAT、Nrf2、PKC、JNK 和自噬在内的各种信号通路，对细胞代谢和适应产生调节作用。此外，漆黄素的剂量和糖尿病、肥胖等合并症被发现是心脏保护的不利因素。
为了进一步评估和顺利将漆黄素分子应用于 IR 治疗的临床转化，研究人员应密切关注漆黄素可能改变关键心脏保护途径和剂量的潜力，因为漆黄素的功效是组织和细胞类型特异性的，并且因剂量不同而有所不同。
