Zhuo Lingxin, Ma Mingxuan, Zhang Jiayi, Zhou Jiayu, Zheng Yuqi, Liang Aiyin, Sun Qingqing, Liu Jia, Liao Wenting
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China.
Pharmaceuticals (Basel). 2025 Jul 25;18(8):1109. doi: 10.3390/ph18081109.
: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. : Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. : It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. : This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment.
脓毒症诱导的心肌病（SIC）是一种死亡率很高的严重临床病症。芪附汤（QFD）是一种著名的传统中药，具有抗炎、抗氧化和抗凋亡等药理作用，对心血管疾病有良好的治疗效果。本研究旨在揭示芪附汤对SIC的心脏保护作用及其潜在机制。：通过心电图、组织病理学检查和生化指标测定，研究芪附汤对脂多糖诱导的SIC小鼠的心脏保护作用。采用代谢组学和网络药理学策略，初步分析和预测芪附汤抗SIC的机制。进一步应用分子对接和蛋白质印迹法，在体外和体内模型中验证治疗SIC的核心靶点和潜在途径。：研究发现，芪附汤可显著增强心脏功能；减轻心肌损伤；并使血清乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平分别降低28.7%、32.3%、38.6%和36.7%。代谢组学分析表明，芪附汤可调节七条代谢途径，即谷胱甘肽代谢、丙氨酸、天冬氨酸和谷氨酸代谢、花生四烯酸代谢、甘油磷脂代谢、嘌呤代谢、鞘脂代谢和脂肪酸代谢。网络药理学提示，芪附汤的抗SIC作用可能通过肿瘤坏死因子、Toll样受体、NOD样受体、核因子-κB（NF-κB）和过氧化物酶体增殖物激活受体（PPAR）信号通路介导。此外，获得了26个核心靶点。分子对接显示，芪附汤中的芒柄花黄素、山柰酚、槲皮素和（R）-去甲乌药碱等活性成分与PPARα和Toll样受体4（TLR4）具有高亲和力。进一步的蛋白质印迹验证表明，芪附汤可调节NLR家族含pyrin结构域蛋白3（NLRP3）、TLR4、NF-κB、IL-6、TNF-α、环氧化酶-2（COX2）、分泌型磷脂酶A2（sPLA2）、PPARα、肉碱棕榈酰转移酶1B（CPT1B）和肉碱棕榈酰转移酶2（CPT2）的蛋白水平。：本研究表明，芪附汤可通过抑制TLR4/NF-κB/NLRP3炎症通路和激活PPARα/CPT途径调节受损的脂肪酸氧化（FAO）来减轻SIC，突出了芪附汤作为一种有前景的SIC治疗候选药物的地位。
