Pharmacological mechanisms of Fuzheng Huayu formula for Aristolochic acid I-induced kidney fibrosis through network pharmacology.
Pharmacological mechanisms of Fuzheng Huayu formula for Aristolochic acid I-induced kidney fibrosis through network pharmacology.
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DOI：
10.3389/fphar.2022.1056865
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
肾纤维化的特征是肾小管和间质毛细血管的破坏以及细胞外基质蛋白的积累，是慢性肾脏疾病的常见结果，并且具有广泛的病因。纤维化可以影响任何器官，并且具有相似的病理机制。扶正化瘀方（FZHY）作为我国批准的抗肝纤维化药物，还可抑制HgCl2或单侧输尿管梗阻引起的肾脏纤维化。然而，对于 FZHY 对肾纤维化有益作用的机制知之甚少。本研究旨在通过网络药理学分析和体内实验来确定FZHY作用于肾纤维化的机制。对在线数据库的数据进行挖掘和筛选，预测FZHY作用于肾纤维化的靶点相关基因。使用 STRING 和 Cytoscape 构建 FZHY 和 CKD 靶蛋白的蛋白质相互作用 (PPI) 网络。利用马兜铃酸 I (AAI) 诱导的 CKD 小鼠模型，通过检测肾功能、肾纤维化和相关交叉基因来验证 FZHY 对肾纤维化的影响及其潜在机制。总共129个FZHY-CKD交叉蛋白被过滤并构建成蛋白质-蛋白质相互作用网络复合体，并指定为FZHY的潜在靶点。得分最高的基因之一 FOS 及其相关信号通路在 CKD 中更加激活。结果表明，扶正祛邪可通过提高血清肌酐、血尿素氮水平，缓解肾组织胶原过度沉积发挥抗肾纤维化作用，并可降低TNF-α、IL-1β、IL-6水平，抑制MAPK/FOS信号分子表达。我们的研究结果为通过网络药理学预测 FZHY 对 CKD 的影响提供了见解。 FZHY 可以保护肾脏免受 AAI 引起的炎症损伤，并可以拮抗纤维化肾脏中炎症因子刺激的 MAPK/FOS 激活。这些作用构成了FZHY治疗肾纤维化的机制。
Renal fibrosis, characterized by the destruction of renal tubules and interstitial capillaries and the accumulation of extracellular matrix proteins, is a common outcome of chronic renal diseases and has a wide spectrum of etiologies. Fibrosis can affect any organ and has similar pathological mechanisms. Fuzheng Huayu formula (FZHY), as the approved anti-liver fibrosis medicine in China, also can inhibit the kidney fibrosis induced by HgCl2 or unilateral ureteral obstruction. However, little is known about the mechanisms underlying the beneficial effects of FZHY on renal fibrosis. This study aimed to identify the mechanisms of FZHY acts on renal fibrosis through network pharmacological analysis and in vivo experiments. Data from online databases were mined and screened to predict the target related genes of FZHY acts on renal fibrosis. The STRING and Cytoscape were used to construct the protein-protein interaction (PPI) networks for FZHY and CKD target proteins. Mouse models with CKD induced by Aristolochic Acid I (AAI) were used to validate the effects of FZHY on renal fibrosis and their underlying mechanisms by detecting kidney function, renal fibrosis, and related intersection genes. A total of 129 FZHY–CKD crossover proteins were filtered and constructed into a protein–protein interaction network complex and designated as the potential targets of FZHY. One of the highest-scoring genes, FOS, and its related signaling pathways were more activated in CKD. The results demonstrated that FZHY can exert an anti-renal fibrosis effect by improving the levels of serum creatinine and blood urea nitrogen and alleviating excessive collagen deposition in kidney tissue, FZHY also could reduce the levels of TNF-α, IL-1β, and IL-6 and inhibit the expression of MAPK/FOS signal molecules. Our study findings provide insights into predicting the effects of FZHY on CKD through network pharmacology. FZHY can protect the kidney from inflammatory injury caused by AAI and can antagonize inflammatory factor-stimulated MAPK/FOS activation in fibrotic kidneys. These effects constitute the mechanisms of FZHY for renal fibrosis.
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影响因子：
5.6
作者：
Jadot I;Declèves AE;Nortier J;Caron N
通讯作者：
Caron N
DOI：
10.1016/s0140-6736(18)31694-5
发表时间：
2018-11-10
期刊：
Lancet (London, England)
影响因子：
--
作者：
Foreman KJ;Marquez N;Dolgert A;Fukutaki K;Fullman N;McGaughey M;Pletcher MA;Smith AE;Tang K;Yuan CW;Brown JC;Friedman J;He J;Heuton KR;Holmberg M;Patel DJ;Reidy P;Carter A;Cercy K;Chapin A;Douwes-Schultz D;Frank T;Goettsch F;Liu PY;Nandakumar V;Reitsma MB;Reuter V;Sadat N;Sorensen RJD;Srinivasan V;Updike RL;York H;Lopez AD;Lozano R;Lim SS;Mokdad AH;Vollset SE;Murray CJL
通讯作者：
Murray CJL
BATMAN-TCM：中药分子机制生物信息学分析工具
影响因子：
4.6
作者：
Liu Z;Guo F;Wang Y;Li C;Zhang X;Li H;Diao L;Gu J;Wang W;Li D;He F
通讯作者：
He F
影响因子：
5.5
作者：
通讯作者：
--
影响因子：
3.7
作者：
Nakagawa S;Nishihara K;Miyata H;Shinke H;Tomita E;Kajiwara M;Matsubara T;Iehara N;Igarashi Y;Yamada H;Fukatsu A;Yanagita M;Matsubara K;Masuda S
通讯作者：
Masuda S