Crocin Protects Podocytes Against Oxidative Stress and Inflammation Induced by High Glucose Through Inhibition of NF-κB

Abstract

Background/Aims: Diabetic nephropathy (DN) is a microangiopathic disease characterized by excessive urinary albumin excretion, which occurs in 30% of patients with diabetes mellitus. It is the second leading cause of end-stage renal diseases in China. Nuclear factor-kappa B (NF-κB) is reported to be closely correlated with the inflammation underlying diabetes-associated renal damage. Crocin, a plant-derived compound, has antioxidant properties that may inhibit NF-κB. Methods: In the present study, we used a conditionally immortalized mouse podocyte cell line to explore whether crocin could effectively block albuminuria. Cells were incubated with 15 or 25 mM D-glucose to mimic diabetic conditions. The expression of Wilms tumor 1 (WT-1) and synaptopodin was evaluated to identify differentiated podocytes, and the expression of nephrin, podocin, and CD2ap was measured as markers of slit diaphragms, the main structures within the glomerular filtration barrier. Results: The high-glucose conditions led to reduced nephrin, podocin, and CD2ap expression, which was prevented by pretreatment with crocin. The oxidative stress and pro-inflammatory response of podocytes associated with DN induced by high glucose were also reduced by crocin pretreatment. Phosphorylated IκBα (p-IκBα) expression induced by high glucose was also significantly decreased by crocin pretreatment. Moreover, pyrrolidine dithiocarbamate, a NF-κB inhibitor, pyrrolidine dithio carbamate, augmented the protective effects of crocin. Conclusion: Our results demonstrate a protective role of crocin against damage to podocytes and slit diaphragms under high-glucose conditions via inhibition of NF-κB. This study presents a potential therapy for DN and contributes to the understanding of the mechanism underlying DN.

Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways

“…# p < 0.05 vs. control group, *p < 0.05 vs. LPS group participate in hemodynamics [5][6][7][8]25]. As shown in previous reports, crocin had an important protective effects in several diseases by affecting on cell apoptosis, arteriosclerosis, oxidation, and inflammation [15][16][17][18][19]. The present study demonstrated that pretreatment with crocin effectively improved the pulmonary edema associated with albumin leakage by maintaining the integrity of glycocalyx in LPS-induced ARDS mice.…”

“…Otherwise, HMGB-1 as an important late inflammatory factor can trigger the intracellular NF-κB signaling pathway and aggravate serious injury [29]. As shown in previous reports, crocin had a strong anti-inflammatory effect in diabetic nephropathy model [18]. The results of this study also showed that crocin had the same strong anti-inflammatory effect in LPS-induced ARDS cell and animal models.…”

“…Crocin is an ester glycoside extracted from saffron. As one of the main active constituents of saffron, crocin has many pharmacological effects, such as anti-oxidation [15], anti-arteriosclerosis [16], anti-apoptosis [17], and anti-inflammatory [18]. However, no studies have reported the effects of crocin on endothelial glycocalyx, HMGB-1, NF-κB, and MAPK signaling pathways in LPS-induced ARDS mice and LPS-stimulated HUVECs.…”

Activation of the Nrf2-ARE Pathway Ameliorates Hyperglycemia-Mediated Mitochondrial Dysfunction in Podocytes Partly Through Sirt1

“…DKD rat models have shown that early glomerular changes involve podocyte injury without mesangial expansion [8], and a correlation between the rate of albumin excretion and a drop in podocyte numbers has been found in patients with DKD [9,10]. The progression of diabetic nephropathy in both type-1 and type-2 diabetes has been associated with podocyte loss [11,12].…”

Clinical and metabolic responses to crocin in patients under methadone maintenance treatment: A randomized clinical trial

“…In animal models with ischemic stroke, crocin (60 mg/kg) significantly decreased MDA values and enhanced activity of superoxide dismutase and glutathione levels (Vakili, Einali, & Bandegi, ). In addition, crocin intake downregulated gene expression of TNF‐α, interleukin (IL) 8, and IL‐10 and significantly suppressed oxidative stress (S. Li et al, ). Furthermore, receiving saffron and crocin (30 mg daily) for 12 weeks was correlated with improving metabolic syndrome in patients with schizophrenia (Fadai et al, ).…”