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羟基红花黄色素A对脓毒症代谢物网络的调节及对JAK2/STAT1通路的抑制作用

Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsis.

作者信息

Pan Bingbing, Chen Fengting, Shen Siyan, Jiang Yu, Yang Ying, Wang Jia, Liu Yanjuan, Wei Lai, Liu Jitong, Kong Gaoyin, He Xuan, Guo Bing

机构信息

Department of Anesthesiology, Clinical Research Center for Anesthesiology of ERAS in Hunan Province, Hunan Provincial People's Hospital and The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, China.

The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha, 410005, Hunan, China.

出版信息

Sci Rep. 2025 Jul 16;15(1):25861. doi: 10.1038/s41598-025-11545-2.

DOI:10.1038/s41598-025-11545-2
PMID:40670549
Abstract

Sepsis, a severe infectious disease causing multiple organ dysfunction, requires further exploration of its pathomechanisms and therapeutic options. Hydroxysafflor Yellow A (HYSA), extracted from Carthamus tinctorius L, has shown anti-inflammatory and antioxidant properties effective in treating sepsis, though its precise mechanism remains unclear. In this study, a cecum ligation puncture (CLP) model was used to evaluate HYSA's effects on sepsis-induced organ injury. HYSA (300 mg/kg) was administered intraperitoneally 4 h post-CLP. Results showed that HYSA inhibited the inflammatory response and improved pathological scores in the liver, lungs, and kidneys. Metabolomics analysis identified key metabolites and pathways influenced by HYSA, including nicotinate and nicotinamide metabolism and glycine/serine metabolism. Network pharmacology and molecular docking identified JAK2/STAT1 as potential targets, with Western blotting confirmed that HYSA inhibits JAK2/STAT1 phosphorylation. These findings suggest that HYSA protects against sepsis-induced organ injury by regulating metabolic networks and modulating the JAK2/STAT1 pathway.

摘要

脓毒症是一种导致多器官功能障碍的严重传染病,需要进一步探索其发病机制和治疗方案。从红花中提取的羟基红花黄色素A(HYSA)已显示出抗炎和抗氧化特性,对治疗脓毒症有效,但其确切机制仍不清楚。在本研究中,采用盲肠结扎穿刺(CLP)模型评估HYSA对脓毒症诱导的器官损伤的影响。在CLP后4小时腹腔注射HYSA(300mg/kg)。结果表明,HYSA抑制了炎症反应,改善了肝脏、肺和肾脏的病理评分。代谢组学分析确定了受HYSA影响的关键代谢物和途径,包括烟酸和烟酰胺代谢以及甘氨酸/丝氨酸代谢。网络药理学和分子对接确定JAK2/STAT1为潜在靶点,蛋白质免疫印迹法证实HYSA抑制JAK2/STAT1磷酸化。这些发现表明,HYSA通过调节代谢网络和调节JAK2/STAT1途径来预防脓毒症诱导的器官损伤。

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本文引用的文献

1
Combining Network Pharmacology, Molecular Docking and Experimental Validation to Explore the Effects and Mechanisms of Indirubin on Acute Lymphoblastic Leukemia.结合网络药理学、分子对接和实验验证以探究靛玉红对急性淋巴细胞白血病的作用及机制
Drug Des Devel Ther. 2025 Feb 18;19:1083-1103. doi: 10.2147/DDDT.S500249. eCollection 2025.
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Repression of JAK2-STAT1 and PD-L1 by CEP-33779 ameliorates the LPS-induced decline in phagocytic activity of alveolar macrophages and mitigates lung injury in mice.CEP-33779对JAK2-STAT1和PD-L1的抑制作用改善了脂多糖诱导的肺泡巨噬细胞吞噬活性下降,并减轻了小鼠的肺损伤。
Front Immunol. 2024 Nov 26;15:1472425. doi: 10.3389/fimmu.2024.1472425. eCollection 2024.
3
Hydroxysafflor yellow A, a natural food pigment, ameliorates atherosclerosis in ApoE mice by inhibiting the SphK1/S1P/S1PR3 pathway.
羟基红花黄色素A,一种天然食用色素,通过抑制鞘氨醇激酶1/1-磷酸鞘氨醇/1-磷酸鞘氨醇受体3通路改善载脂蛋白E基因敲除小鼠的动脉粥样硬化。
Food Sci Nutr. 2024 Sep 14;12(11):8939-8955. doi: 10.1002/fsn3.4466. eCollection 2024 Nov.
4
NAD activates olfactory receptor 1386 to regulate type I interferon responses in YM infection.NAD 激活嗅觉受体 1386 以调节 YM 感染中的 I 型干扰素反应。
Proc Natl Acad Sci U S A. 2024 Jun 4;121(23):e2403796121. doi: 10.1073/pnas.2403796121. Epub 2024 May 29.
5
Combined metabolomic and proteomic analysis of sepsis related acute liver injury and its pathogenesis research.脓毒症相关急性肝损伤的代谢组学和蛋白质组学联合分析及其发病机制研究。
Int Immunopharmacol. 2024 Mar 30;130:111666. doi: 10.1016/j.intimp.2024.111666. Epub 2024 Feb 26.
6
Serine synthesis sustains macrophage IL-1β production via NAD-dependent protein acetylation.丝氨酸合成通过 NAD 依赖性蛋白乙酰化来维持巨噬细胞 IL-1β 的产生。
Mol Cell. 2024 Feb 15;84(4):744-759.e6. doi: 10.1016/j.molcel.2024.01.002. Epub 2024 Jan 23.
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