Magnolol Reduces Renal Ischemia and Reperfusion Injury via Inhibition of Apoptosis

Abstract

Magnolol, a constituent of the bark of Magnolia officinalis, has been reported to decrease myocardial stunning and infarct size. In this study, we investigated whether magnolol can reduce renal ischemia and reperfusion (I/R) injury. Renal I/R, induced by a 60-min occlusion of bilateral renal arteries and a 24-h reperfusion, significantly increased blood urea nitrogen (BUN) and creatinine levels, and caused histological damage to the kidneys of rats. Apoptosis, as evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and caspase-3 activation, was significantly increased in the kidneys. Furthermore, serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were significantly elevated, while the interleukin-10 (IL-10) level was suppressed. However, intravenous pretreatment with magnolol at doses of 0.003 mg/kg and 0.006 mg/kg 10 min before renal I/R significantly limited the increases of BUN, creatinine, the histological damage, and apoptosis in the kidneys. The increases in TNF-α, IL-1β, and IL-6, and the decrease in IL-10 were also significantly inhibited. Additionally, magnolol increased Bcl-2 and decreased Bax in the kidneys. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/ 2), was elevated, while phosphorylation of the pro-apoptotic mitogen-activated protein kinases, including p38 and c-Jun N-terminal kinase (JNK), was suppressed. In conclusion, magnolol reduces renal I/R injury. The underlying mechanisms for this effect might be related to the prevention of apoptosis, possibly via the inhibition of both extrinsic and intrinsic apoptotic pathways, including the reduction of TNF-α production and the modulation of pro-and anti-apoptotic signaling elements.

Effect of sodium (S)-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway

“…However, reports are inconsistent. One study noted that IR does not increase the concentrations of these cytokines ( Zhu et al, 2014 ), whereas other studies have reported increases in cytokine concentrations in proportion to the severity of injury ( Shen et al, 2018 ; Tang et al, 2017 ; Zhang et al, 2018 ; Zhang et al, 2015 ). In this work, we did not observe significant increases in the concentrations of IL-1β, IL-6, or TNF-α.…”

CD47 Deficiency Attenuates Isoproterenol-Induced Cardiac Remodeling in Mice

“…Five random fields per slide (five slides per animal, seven animals per group) were examined. The number of TUNEL-positive cell nuclei (numerator) and the total number of cell nuclei (denominator) were counted as previously described [46]. The percentage of TUNEL-positive cells in each field was analyzed using Image-Pro Plus 6.0 software.…”

Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer

“…MAG is reported to possess an array of pharmacological effects including anti-oxidant [70], anti-inflammatory [71], anti-bacterial [10], anti-thrombotic or anti-platelet [72], anti-stress [73], anti-anxiety, anti-Alzheimer [74], anti-stroke [75], hypoglycemic [76], smooth muscle relaxant [77,78], weight control [79], anti-dyspeptic/prokinetic [80], anti-epileptic [81], and hepatoprotective effects [82]. Small-scale clinical studies on MAG and its interaction with gamma-aminobutyric acid-A (GABA-A) and muscarinic receptors show that it helps in decreasing the anxiety levels in patients [78,83,84,85].…”