Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：管理缺血性心脏病的主要治疗策略是通过手术方法恢复心肌缺血区域的灌注，这通常会导致不可避免的损伤，称为缺血再灌注损伤（IR）。Fisetin是一种有效的类黄酮，具有抗氧化和抗炎特性，在体外和体内模型中证明对IR损伤具有心脏保护作用，除了它对癌症有前途的健康益处，糖尿病,和神经退行性疾病。
目的：非塞汀减弱心肌IR的潜力尚无定论，因为非塞汀的有效性需要更多了解其可能的靶位点和潜在的不同机制。考虑到最近对非塞汀作为药理学药物的科学兴趣激增，这篇综述不仅更新了现有的非塞素的临床前和临床研究及其潜在机制，还总结了其在IR保护过程中的可能靶标。
方法：我们使用搜索引擎Pubmed，PMC,科学直接，Google,和2006-2021年出版的研究门。从数据库中提取相关研究,结合以下关键词进行综述:心肌缺血再灌注损伤,天然产品,类黄酮，Fisetin,PI3K,JAK-STAT,Nrf2,PKC,JNK,自噬。
结果：据报道，Fisetin通过延迟凝血时间可有效减轻IR损伤，保留线粒体功能，减少氧化应激，并抑制GSK3β。但它未能保护受到IR攻击的患病心肌细胞。正如本次审查所讨论的那样，非塞素不仅可以作为常规的抗氧化剂和抗炎剂发挥其生物学作用，而且还可以通过直接作用于包含PI3K的各种信号通路对细胞代谢和适应发挥调节作用，JAK-STAT,Nrf2,PKC,JNK,和自噬。此外，非塞素的剂量和糖尿病和肥胖等合并症被发现是心脏保护的有害因素。
结论：为了进一步评估和顺利临床翻译非塞素分子在IR治疗中，研究人员应密切关注非塞素可能改变关键心脏保护途径和剂量的潜力，因为非塞汀的功效是组织和细胞类型特异性的，并且随剂量的不同而变化。
目的：非塞汀减弱心肌IR的潜力尚无定论，因为非塞汀的有效性需要更多了解其可能的靶位点和潜在的不同机制。考虑到最近对非塞汀作为药理学药物的科学兴趣激增，这篇综述不仅更新了现有的非塞素的临床前和临床研究及其潜在机制，还总结了其在IR保护过程中的可能靶标。
方法：我们使用搜索引擎Pubmed，PMC,科学直接，Google,和2006-2021年出版的研究门。从数据库中提取相关研究,结合以下关键词进行综述:心肌缺血再灌注损伤,天然产品,类黄酮，Fisetin,PI3K,JAK-STAT,Nrf2,PKC,JNK,自噬。
结果：据报道，Fisetin通过延迟凝血时间可有效减轻IR损伤，保留线粒体功能，减少氧化应激，并抑制GSK3β。但它未能保护受到IR攻击的患病心肌细胞。正如本次审查所讨论的那样，非塞素不仅可以作为常规的抗氧化剂和抗炎剂发挥其生物学作用，而且还可以通过直接作用于包含PI3K的各种信号通路对细胞代谢和适应发挥调节作用，JAK-STAT,Nrf2,PKC,JNK,和自噬。此外，非塞素的剂量和糖尿病和肥胖等合并症被发现是心脏保护的有害因素。
结论：为了进一步评估和顺利临床翻译非塞素分子在IR治疗中，研究人员应密切关注非塞素可能改变关键心脏保护途径和剂量的潜力，因为非塞汀的功效是组织和细胞类型特异性的，并且随剂量的不同而变化。
