Drug Design, Development and Therapy (Apr 2020)
Isoliquiritigenin Attenuates UUO-Induced Renal Inflammation and Fibrosis by Inhibiting Mincle/Syk/NF-Kappa B Signaling Pathway
Abstract
Yuan Liao,1,* Rui-zhi Tan,1,* Jian-chun Li,1 Tong-tong Liu,1 Xia Zhong,1 Ying Yan,1 Jie-ke Yang,1 Xiao Lin,1 Jun-ming Fan,2 Li Wang1 1Research Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 2Chengdu Medical College, Chengdu, Sichuan 610000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li WangResearch Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital, Southwest Medical University, 319 # Zhongshan Road, Luzhou, Sichuan 646000, People’s Republic of ChinaTel +86 0830 3161222Email [email protected]: 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.Keywords: Isoliquiritigenin, Mincle, macrophage, CKD, inflammation, fibrosis
