Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
Drug Des Devel Ther. 2020 Oct 8;14:4135-4148. doi: 10.2147/DDDT.S274256. eCollection 2020.
Diabetic nephropathy (DN) has become an increasing threat to health, and inflammation and fibrosis play important roles in its progression. Wogonin, a flavonoid, has been proven to suppress inflammation and fibrosis in various diseases, including acute kidney injury. This study aimed at investigating the effect of wogonin on diabetes-induced renal inflammation and fibrosis.
Streptozotocin (STZ)-induced diabetic mouse models received gavage doses of wogonin (10, 20, and 40 mg/kg) for 12 weeks. Metabolic indices from blood and urine and pathological damage of glomerulus in the diabetic model were assessed. Glomerular mesangial cells SV40 were cultured in high glucose (HG) medium containing wogonin at concentrations of 1.5825, 3.125, and 6.25 μg/mL for 24 h. Inflammation and fibrosis indices were evaluated by histopathological, Western blotting, and PCR analyses.
Wogonin treatment ameliorated albuminuria and histopathological lesions in diabetic mice. Inflammatory cytokines, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and related signaling pathway NF-κB were downregulated after the administration of wogonin in vivo and in vitro. Furthermore, wogonin reduced the expression of extracellular matrix (ECM), including fibronectin (FN), collagen IV (Col-IV), α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) in the kidneys of diabetic mice and HG-induced mesangial cells. Moreover, the inhibition of TGF-β1/Smad3 pathway might be responsible for these changes.
Wogonin may ameliorate renal inflammation and fibrosis in diabetic nephropathy by inhibiting the NF-κB and TGF-β1/Smad3 signaling pathways.
糖尿病肾病（DN）已成为健康的一大威胁，炎症和纤维化在其进展中起着重要作用。汉黄芩素是一种黄酮类化合物，已被证明可抑制包括急性肾损伤在内的多种疾病中的炎症和纤维化。本研究旨在探讨汉黄芩素对糖尿病诱导的肾脏炎症和纤维化的作用。
链脲佐菌素（STZ）诱导的糖尿病小鼠模型接受汉黄芩素（10、20 和 40mg/kg）灌胃 12 周。评估糖尿病模型的血液和尿液代谢指标以及肾小球的病理损伤。将肾小球系膜细胞 SV40 在含有汉黄芩素的高糖（HG）培养基中培养，浓度分别为 1.5825、3.125 和 6.25μg/mL，培养 24h。通过组织病理学、Western blot 和 PCR 分析评估炎症和纤维化指标。
汉黄芩素治疗改善了糖尿病小鼠的蛋白尿和组织病理学损伤。体内和体外给予汉黄芩素后，炎症细胞因子，如单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和相关信号通路 NF-κB 的表达下调。此外，汉黄芩素降低了糖尿病小鼠肾脏和 HG 诱导的系膜细胞中细胞外基质（ECM）的表达，包括纤连蛋白（FN）、IV 型胶原（Col-IV）、α-平滑肌肌动蛋白（α-SMA）和转化生长因子-β1（TGF-β1）。此外，抑制 TGF-β1/Smad3 通路可能是这些变化的原因。
汉黄芩素可能通过抑制 NF-κB 和 TGF-β1/Smad3 信号通路改善糖尿病肾病中的肾脏炎症和纤维化。
