Ashrafizadeh Milad, Samarghandian Saeed, Hushmandi Kiavash, Zabolian Amirhossein, Shahinozzaman Md, Saleki Hossein, Esmaeili Hossein, Raei Mehdi, Entezari Maliheh, Zarrabi Ali, Najafi Masoud
Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla, 34956Istanbul, Turkey.
Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
Curr Mol Pharmacol. 2021 Oct 25;14(4):537-558. doi: 10.2174/1874467213666201217122544.
Ischemia/reperfusion (I/R) injury is a serious pathologic event that occurs due to restriction in blood supply to an organ, followed by hypoxia. This condition leads to enhanced levels of pro-inflammatory cytokines such as IL-6 and TNF-α, and stimulation of oxidative stress via enhancing reactive oxygen species (ROS) levels. Upon reperfusion, blood supply incz reases, but it deteriorates condition and leads to the generation of ROS, cell membrane disruption and finally, cell death. Plant derived-natural compounds are well-known due to their excellent antioxidant and anti-inflammatory activities. Quercetin is a flavonoid exclusively found in different vegetables, herbs, and fruits. This naturally occurring compound possesses different pharmacological activities making it an appropriate option in disease therapy. Quercetin can also demonstrate therapeutic effects via affecting molecular pathways such as NF-κB, PI3K/Akt and so on. In the present review, we demonstrate that quercetin administration is beneficial in ameliorating I/R injury via reducing ROS levels, inhibition of inflammation, and affecting molecular pathways such as TLR4/NF-κB, MAPK and so on. Quercetin can improve cell membrane integrity via decreasing lipid peroxidation. Apoptotic cell death is inhibited by quercetin via downregulation of Bax, and caspases, and upregulation of Bcl-2. Quercetin is able to modulate autophagy (inhibition/induction) in decreasing I/R injury. Nanoparticles have been applied for the delivery of quercetin, enhancing its bioavailability and efficacy in the alleviation of I/R injury. Noteworthy, clinical trials have also confirmed the capability of quercetin in reducing I/R injury.
缺血/再灌注（I/R）损伤是一种严重的病理事件，它是由于器官血液供应受限，随后出现缺氧而发生的。这种情况会导致促炎细胞因子如白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平升高，并通过提高活性氧（ROS）水平来刺激氧化应激。再灌注时，血液供应增加，但病情会恶化，导致ROS生成、细胞膜破坏，最终导致细胞死亡。植物来源的天然化合物因其出色的抗氧化和抗炎活性而闻名。槲皮素是一种仅存在于不同蔬菜、草药和水果中的类黄酮。这种天然存在的化合物具有多种药理活性，使其成为疾病治疗的合适选择。槲皮素还可以通过影响核因子κB（NF-κB）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）等分子途径来发挥治疗作用。在本综述中，我们证明槲皮素给药通过降低ROS水平、抑制炎症以及影响Toll样受体4（TLR4）/NF-κB、丝裂原活化蛋白激酶（MAPK）等分子途径，对改善I/R损伤有益。槲皮素可以通过减少脂质过氧化来改善细胞膜完整性。槲皮素通过下调Bax和半胱天冬酶，并上调Bcl-2来抑制凋亡细胞死亡。槲皮素能够调节自噬（抑制/诱导）以减轻I/R损伤。纳米颗粒已被用于递送槲皮素，提高其在减轻I/R损伤方面的生物利用度和疗效。值得注意的是，临床试验也证实了槲皮素减轻I/R损伤的能力。
