Department of Oncology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430065, P.R. China.
Department of Endocrinology, Second Affiliated Hospital of Wuhan University of Science and Technology, Wuhan 430065, P.R. China.
Aging (Albany NY). 2023 Sep 18;15(19):10072-10088. doi: 10.18632/aging.205033.
This study aimed to investigate the pharmacological effects and molecular mechanisms of Dahuang-Gancao Decoction (DHGC) on acute kidney injury (AKI). Network pharmacology was utilized to analyze the key targets of DHGC against AKI. These targets were used to construct a protein-protein interaction (PPI) network, which was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment to predict the mechanism of action. Based on the network pharmacological analysis, Sirtuin 3 (SIRT3) was identified as a key target, and apoptosis was suggested as a mechanism of DHGC for AKI treatment. Subsequently, an AKI mouse model was induced using lipopolysaccharide (LPS), and the study demonstrated that DHGC gradient intervention significantly reduced plasma urea and creatinine levels in AKI mice, ameliorated renal pathological changes, reduced apoptosis, and lowered serum inflammatory factors. The mechanism of DHGC's anti-AKI effect may lie in the activation of the SIRT3/NRF2/HO-1 signaling pathway, which plays an antiapoptotic role in renal cells. In summary, DHGC improved LPS-induced AKI in mice by activating the SIRT3/NRF2/HO-1 signaling pathway. These findings shed light on the potential clinical application of DHGC for the treatment of nephropathy.
本研究旨在探讨大黄甘草汤（DHGC）对急性肾损伤（AKI）的药理作用和分子机制。采用网络药理学方法分析 DHGC 治疗 AKI 的关键靶点。这些靶点用于构建蛋白质-蛋白质相互作用（PPI）网络，使用基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析来预测作用机制。基于网络药理学分析，鉴定出 Sirtuin 3（SIRT3）是一个关键靶点，细胞凋亡被认为是 DHGC 治疗 AKI 的作用机制之一。随后，采用脂多糖（LPS）诱导 AKI 小鼠模型，研究表明 DHGC 梯度干预可显著降低 AKI 小鼠的血浆尿素和肌酐水平，改善肾脏病理变化，减少细胞凋亡，降低血清炎症因子。DHGC 的抗 AKI 作用机制可能在于激活 SIRT3/NRF2/HO-1 信号通路，在肾细胞中发挥抗细胞凋亡作用。总之，DHGC 通过激活 SIRT3/NRF2/HO-1 信号通路改善 LPS 诱导的 AKI。这些发现为 DHGC 在治疗肾病方面的潜在临床应用提供了依据。
