Kaempferol Improves Lung Ischemia-Reperfusion Injury via Antiinflammation and Antioxidative Stress Regulated by SIRT1/HMGB1/NF-κB Axis

Abstract

Trauma, organ transplantation, and thromboembolism are the main causes of lung ischemia-reperfusion injury (LIRI), and new therapies and drugs are urgent to relieve LIRI. In preliminary experiment, authors found that kaempferol could improve LIRI in rats, and the current study further explored its possible mechanism. The model of rat LIRI was established and appropriate research methods were implemented. Results shown that kaempferol could significantly improve LIRI, inhibit release of inflammatory factors including interleukin (IL) 6 and tumor necrosis factor (TNF) a in bronchoalveolar lavage fluid, and reduce oxidative stress reaction. Western blotting was used to detect protein expression levels and found that kaempferol could up-regulate the protein expressions of phosphorylated (p-) p65 and p65, and down-regulate the protein expression of sirtuin (SIRT) 1. Immunofluorescence was used to localize the expression of high mobility group box (HMGB) 1 and found its higher expression in outside of nucleus. However, the above effects of kaempferol on LIRI markedly attenuated by EX 527, a selective inhibitor of SIRT 1. Taken together, we first reported the protective effect of kaempferol on rat LIRI and confirmed that kaempferol's antiinflammation and antioxidative stress involving the SIRT1/ HMGB1/NF-kB axis.

Kaempferol Alleviates Oxidative Stress and Apoptosis Through Mitochondria-dependent Pathway During Lung Ischemia-Reperfusion Injury

“…In previous studies, we have confirmed that kaempferol exerts anti-LIRI by increasing SIRT1 activity (Yang et al, 2020). In this study, we found that kaempferol can improve the stability of mitochondrial membrane potential and inhibit the opening of mPTP of L2 cells after A/R, up-regulate the levels of Bcl-2 and mitochondrial cytochrome c while downregulating the levels of Bax and cytoplasmic cytochrome c in L2 cells after A/R or lung tissue of rats after I/R.…”

“…The rats were randomly divided into five groups with six rats in each as follows. 1) The control group (Control), as previous ( Yang et al, 2020 ), the rats were intraperitoneally injected with 2 ml vehicle for 7 days. One hour after the last administration, rats were anesthetized with pentobarbital sodium (50 mg/kg) intraperitoneally, performed thoracotomy, exposed the trachea and then closed the chest immediately.…”

“…One hour after the last administration, rats were anesthetized with pentobarbital sodium (50 mg/kg) intraperitoneally, performed thoracotomy, exposed the trachea and then closed the chest immediately. 2) I/R group, the rats were intraperitoneally injected with 2 ml vehicle for 7 days, then operated 1 h after the last administration as previous reported ( Yang et al, 2020 ). Briefly, after the rats were anesthetized with pentobarbital sodium, the trachea was surgically exposed and mechanical ventilation was performed with 40% O 2 .…”

“…The development of new therapies or drugs to prevent and treat LIRI is an urgent matter ( Bonservizi et al, 2014 ). In our previous study, we found that kaempferol, a natural flavonoid, has a significant effect on anti-LIRI in rats, and its mechanism may be achieved through targeting activation of sirtuin (SIRT) 1 protein ( Yang et al, 2020 ). However, its specific mechanism still needs to be further improved.…”

Sephadex® LH-20, Isolation, and Purification of Flavonoids from Plant Species: A Comprehensive Review

“…Kaempferol ( 130 ) (3,4′,5,1-tetrahydroxyflavoune) is an aglycone flavonol which is naturally occurred in many plants’ parts through the phenylpropanoid pathway [ 102 , 103 ]. Pharmacological and biological activities of this nutraceutical compound have been extensively studied and reported to possess significant antiproliferative, cytotoxicity, anti-inflammatory, antioxidant, and antidiabetic activities [ 104 , 105 , 106 , 107 , 108 , 109 ].…”