<p>Isoliquiritigenin Attenuates UUO-Induced Renal Inflammation and Fibrosis by Inhibiting Mincle/Syk/NF-Kappa B Signaling Pathway</p>

Abstract

Chronic kidney disease (CKD) is a global nephrotic syndrome characterized by chronic inflammation, oxidative stress and fibrosis in the kidney. Isoliquiritigenin (ISL), a flavonoid from licorice, has historically been reported to inhibit innate immune responses to inflammation and fibrosis in vivo. However, the effect of ISL on CKD progression is largely unknown. Materials and Methods: In this study, we employed the inflammatory and fibrotic models of LPS/TGF-β-induced bone marrow-derived macrophages (BMDM) in vitro and unilateral ureteral obstruction (UUO) model in vivo to explore the potential effects and mechanism of ISL on renal inflammation and fibrosis. Results: Our results manifest that ISL improved UUO-induced renal dysfunction and reduced tubular damage with a significantly downregulated mRNA expression and secretion of IL-1β, IL-6, TNF-α and MCP-1 in vitro and in vivo. It is worth noting that ISL can strongly inhibit the mRNA and protein expression of Mincle (macrophage-induced c-type lectin) in BMDM and UUO. ISL inhibited the phosphorylation of Syk and NF-kappa B and simultaneously reduced the expression of α-SMA and Col III in vivo and in vitro. More interestingly, when dealing with TDB, a ligand of Mincle, it revealed significant reversal of protein expression levels as that observed with ISL. The expressions of IL-1β, IL-6, TNF-α, iNOS, p-Syk, p-NF-kappa B, α-SMA and FN in BMDM inflammatory model were significantly upregulated with TDB treatment. This confirms that ISL inhibits inflammation and fibrosis of macrophage by suppressing Mincle/Syk/NF-kappa B signaling pathway. Conclusion: To conclude, ISL protects UUO-induced CKD by inhibiting Mincle-induced inflammation and suppressing renal fibrosis, which might be a specific renal protective mechanism of ISL, making it a novel drug to ameliorate CKD.

Chalcone Derivatives: Role in Anticancer Therapy

“…Similarly, 2-hydroxy-3’,5,5’-trimethoxychalcone (DK-139) ( 58 , Figure 13 ) inhibited the Toll-like receptor 4-mediated inflammatory response through suppression of the Akt//IKK/NF-κB signaling pathway in BV2 microglial cells [ 148 ]. In addition, isoliquiritigenin [ 149 , 150 , 151 ], flavokawain A and B [ 152 ], licochalcone A [ 153 ], cardamonin [ 154 , 155 , 156 ] and xanthohumol [ 157 ] all showed anti-inflammatory and anticancer activities by preventing the degradation of IκBα and in turn blocking NF-κB activation. Moreover, Venkateswararao et al evaluated the inhibitory activity of a series of chalcone derivatives ( 59 , IC 50 : 1.17–3.43 µM) against NF-κB and their in vitro antiproliferative activity against various human cancer cell lines, and they found a good correlation between NF-κB inhibition through these derivatives and antiproliferative activity [ 158 ].…”

The potential of glycyrrhizin and licorice extract in combating COVID-19 and associated conditions

“…Isoliquiritigenin alleviated LPS-induced acute kidney injury by inhibition of the NF-κB pathway and TNF-alpha-induced release of HMGB ( Chi et al, 2017 ; Tang et al, 2018 ). Moreover, Isoliquiritigenin ameliorates renal Inflammation and fibrosis induced by unilateral ureteral obstruction ( Liao et al, 2020 ). It also, suppressed the Ang II-induced hypertensive renal injury via inhibiting inflammation cytokines, excessive deposition, and Nrf2 and NF-κB pathways ( Xiong et al, 2018 ).…”

Stem cells in the treatment of renal fibrosis: a review of preclinical and clinical studies of renal fibrosis pathogenesis

“…Huber and others confirmed that inhibiting NF-κB signaling in Ras-transfected epithelial cells could prevent the occurrence of EMT, and activation of this pathway could promote the morphological transformation of cells to mesenchymal cells in the absence of TGF-β. In addition, the inhibition of NF-κB activity in mesenchymal cells can lead to a reversal of the EMT process, suggesting that NF-κB is necessary for the induction and maintenance of EMT [ 97 ]. NF-κB may be involved in the regulation of renal fibrosis, but the specific mechanism remains to be further studied (Fig.…”