Xiang Huilong, Lei Huan, Liu Ziyuan, Liu Yongjie, Li Yang, Qiu Yinsheng, Xu Lingyun
College of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, China.
School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
Toxicol Appl Pharmacol. 2021 Aug 1;424:115594. doi: 10.1016/j.taap.2021.115594. Epub 2021 May 24.
Oxidative stress and inflammation in kidney are the main causes for hyperuricemic nephropathy (HN). Baicalin and baicalein, two flavonoids, have anti-inflammatory and anti-oxidative effects and they are interconvertible in the body. In this study, both baicalin and baicalein were administered by intragastric administration (i.g.) or intraperitoneal injection (i.p.) at the dose of 50 mg kg, once a day for 15 consecutive days to HN mice, a model established by i.g. of yeast extract combined with i.p. of potassium oxonate. In HN mice, baicalin and baicalein reduced serum uric acid (SUA) levels and protected kidneys by anti-inflammatory and anti-oxidative effects. Mechanistically, the effect of baicalin and baicalein on reducing SUA levels might due to their inhibitory effect on xanthine oxidase (XO) activity in vivo and in vitro. Furthermore, the mechanisms of baicalin and baicalein against HN were analyzed with network pharmacology and molecular docking technology. The network pharmacology indicated that the protective effects of baicalin and baicalein against HN were mainly related to their down-regulating effects on TLRs, NF-κB, MAPK, PI3K/AKT and NOD-like receptor signaling pathways. Molecular docking indicated high binding affinity of baicalin/baicalein to targets such as AKT1 and MAPK1. In summary, baicalin and baicalein are promising drug candidates for the treatment of HN by inhibiting XO activity, reducing inflammation and cell apoptosis through down-regulating TLRs/NLRP3/NF-κB, MAPK, PI3K/AKT/NF-κB pathways.
肾脏中的氧化应激和炎症是高尿酸血症肾病（HN）的主要病因。黄芩苷和黄芩素这两种黄酮类化合物具有抗炎和抗氧化作用，且它们在体内可相互转化。在本研究中，将黄芩苷和黄芩素以50mg/kg的剂量通过灌胃（i.g.）或腹腔注射（i.p.）给予HN小鼠，每天一次，连续15天。HN小鼠模型是通过灌胃酵母提取物并腹腔注射氧嗪酸钾建立的。在HN小鼠中，黄芩苷和黄芩素通过抗炎和抗氧化作用降低血清尿酸（SUA）水平并保护肾脏。机制上，黄芩苷和黄芩素降低SUA水平的作用可能归因于它们在体内和体外对黄嘌呤氧化酶（XO）活性的抑制作用。此外，运用网络药理学和分子对接技术分析了黄芩苷和黄芩素抗HN的机制。网络药理学表明，黄芩苷和黄芩素对HN的保护作用主要与其对Toll样受体（TLRs）、核因子κB（NF-κB）、丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）和NOD样受体信号通路的下调作用有关。分子对接表明黄芩苷/黄芩素与AKT1和MAPK1等靶点具有高结合亲和力。总之,黄芩苷和黄芩素有望成为治疗HN的候选药物，它们通过抑制XO活性，下调TLRs/NLRP3/NF-κB、MAPK、PI3K/AKT/NF-κB通路来减轻炎症和细胞凋亡。
