04 March 2019 : Animal Research
Calycosin Ameliorates Diabetes-Induced Renal Inflammation via the NF-κB Pathway In Vitro and In VivoYing-ying Zhang1ABCDEF, Rui-zhi Tan2ABCE, Xiao-qin Zhang1BC, Ying Yu1BG, Chen Yu1AG*
Med Sci Monit 2019; 25:1671-1678
BACKGROUND: Diabetic nephropathy (DN), which is one of the primary causes of end-stage renal disease (ESRD), is increasingly diagnosed in patients due to the continuous increase in the prevalence of diabetic mellitus (DM). Astragali Radix, a traditional Chinese herb, is widely administrated to ameliorate the symptoms of diabetes and diabetic nephropathy, but its mechanism is still not yet fully defined. Calycosin (C₁₆H₁₂O₅) is the major active component of Astragali Radix. In this study, we analyzed the role of calycosin in diabetic nephropathy and explored its underlying mechanism.
MATERIAL AND METHODS: Cell activation, inflammatory cytokines expression and secretion, and protein levels were analyzed in cultured mouse tubular epithelial cells (mTEC). db/db mice were intraperitoneally injected with 10 mg/(kg·d) calycosin or control saline for 4 weeks, followed by analysis of structure injury, inflammation, and NF-κB signaling activity.
RESULTS: Our results indicated that TNF-α and IL-1β were significantly induced by advanced glycation end-products (AGEs), but calycosin remarkably reduced the expression of TNF-α and IL-1β in the cultured mouse tubular epithelial cells (mTEC). Calycosin effectively alleviated kidney injury in diabetic kidneys of db/db mice during the progression of diabetic renal injury, indicated by the reduction of histological injury and immunohistochemical of inflammatory cytokines. Mechanistically, we identified calycosin inhibited diabetes-induced inflammation in kidneys by suppressing the phosphorylation of IKBa and NF-κB p65 in vitro and in vivo.
CONCLUSIONS: Calycosin significantly ameliorated diabetes-induced renal inflammation in diabetic renal injury by inhibition of the NF-κB-dependent signaling pathway in vivo and in vitro.
Keywords: Astragalus propinquus, Cytokines, Diabetes Mellitus, Experimental, Drugs, Chinese Herbal, Isoflavones, Kidney, Nephritis, Phosphorylation, Transcription Factor RelA
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