Icariin Improves Sepsis-Induced Mortality and Acute Kidney Injury

Abstract

Objectives: Icariin (ICA) is a bioactive flavonoid with renal protective actions. This study investigated the effects of ICA on renal injury, inflammation, oxidative damage, apoptosis, and survival in a mouse model of cecal ligation and perforation (CLP)-induced sepsis. Methods: Sepsis was induced by CLP. Mice were treated with ICA (30 or 60 mg/kg) for 3 days before CLP. Renal functions, inflammatory responses, oxidative damage, histological changes, apoptosis, and vascular permeability were examined. The effects of ICA on CLP-induced expression of renal nuclear factor-κB (NF-κB), cleaved caspase-3, Bax, and Bcl-2 were evaluated. Results: Mice in the CLP group had a low survival rate and increases in blood urea nitrogen and creatinine levels, proinflammatory cytokine levels, oxidative damage, apoptosis, and vascular permeability. These renal changes were dramatically improved by ICA treatment, especially in the 60 mg/kg ICA group. The detection of molecules involved in the inflammation and apoptosis of the kidney indicated that ICA reduced expression of NF-κB, cleaved caspase-3, and Bax but enhanced expression of Bcl-2. Conclusion: ICA improves CLP-induced mortality and acute kidney injury by inhibiting renal oxidant damage, inflammatory responses, apoptosis, and vascular permeability.

Current Concepts on the Reno-Protective Effects of Phosphodiesterase 5 Inhibitors in Acute Kidney Injury: Systematic Search and Review

“…The main characteristics and results of the human studies evaluating the potential reno-protective effects of PDE5Is are summarized in Table 1 [17,24,38,39]. The main characteristics and results of the animal studies on currently proposed AKI models evaluating the potential reno-protective effects of sildenafil, tadalafil, icariin, vardenafil, zaprinast-udenafil are summarized in Table 2 [23,30,, Table 3 [29,35,45,49,[62][63][64][65][66][67][68][69][70][71][72][73][74], Table 4 [18,75,76], Table 5 [45,77,78], and Table 6 [21,40,79,80], respectively. The main characteristics and results of the animal studies in the AKI-CKD transition spectrum (focusing on renal function and/or structure alterations for up to three months, not fulfilling the KDIGO definition for CKD [6]) evaluating the potential reno-protective effects of sildenafil, tadalafil, icariin, vardenafil, zaprinast-udenafil are summarized in Table A1 [109,110], respectively (Appendix B).…”

“…Depending on the insult type, there are various mechanisms leading to renal damage such as renal vasoconstriction [17], vascular endothelial damage, cytokine expression [18], increase of IL-18, mediating acute tubular necrosis, caspase activity stimulation, p53 up-regulation [19], accumulation of toxic metabolites [20], mast cells/neutrophils activation, reactive oxygen species (ROS) generation causing lipid peroxidation that leads to cellular membrane destruction, excessive intracellular DNA breakdown, energy depletion, intracellular Ca2+ elevation, higher inducible nitric oxide (NO) synthase (iNOS) expression, NO deficiency, intra-parenchymal hemorrhage [21], fibrosis, direct cellular toxicity, tubular obstruction, vascular congestion, activation of angiotensin II axis [22], mitochondrial dysfunction [23], cell cycle arrest in G2 phase, ATPase activity inhibition, and cellular transport modification. ROS activate pro-apoptotic proteins eventually promoting Bax translocation (regulated by PI3K/Akt pathway) to the outer mitochondrial membrane, causing the release of cytochrome c in the cytosol [24].…”

Icariin and Competing Endogenous RNA Network: A Potential Protective Strategy Against Contrast-Induced Acute Kidney Injury

“…Similarly, Xie et al reported a protection of icariin against inflammatory response, apoptosis and vascular permeability in a sepsis-induced AKI mouse model. 24 In another unilateral ureteral obstruction mouse model, icariin also mitigated several proinflammatory factors, such as NF-κB, cyclooxygenase-2 and interleukin 1β. 10 Thus, the universal anti-inflammation and anti-apoptosis effect of icariin may contribute to its remarkable protection in CIAKI model, as the improved renal function and alleviated histological injury were demonstrated in our study.…”

Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats

“…Moreover, polyphenolic antioxidant flavonoid consumption improves endotoxemia and septic condition. Several types of flavonoids improve MODS and increase survival against sepsis [ 36 , 37 , 38 ]. The evidence suggests that the nutrient composition of food affects sepsis progression and its outcomes, but the molecular underlying mechanism has not been completely described.…”