Taraxerone inhibits M1 polarization and alleviates sepsis-induced acute lung injury by activating SIRT1.

IF 5.3 3区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Medicine Pub Date : 2024-11-14 DOI:10.1186/s13020-024-01002-z

Lang Deng, Weixi Xie, Miao Lin, Dayan Xiong, Lei Huang, Xiaohua Zhang, Rui Qian, Xiaoting Huang, Siyuan Tang, Wei Liu

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引用次数: 0

Abstract

Background: Acute lung injury (ALI) is the most lethal disease associated with sepsis, and there is a lack of effective drug treatment. As the major cells of sepsis-induced ALI, macrophages polarize toward the proinflammatory M1 phenotype and secrete multiple inflammatory cytokines to accelerate the disease process through nuclear factor kappa-B (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways. Taraxerone, the main component of the Chinese medicinal Sedum, possesses numerous biological activities. However, uncertainty remains regarding the potential of taraxerone to protect against sepsis-induced ALI. This study aimed to investigate the effects and mechanisms of taraxerone against ALI.

Methods: An animal model for ALI was established by cecal ligation and puncture and treated with taraxerone via intraperitoneal administration. The protective effect of taraxerone on the lungs was analyzed using H&E staining, dihydroethidium staining, ELISA kits, cell counting, myeloperoxidase kit, malondialdehyde kit, glutathione kit, superoxide dismutase kit and flow cytometry. Western blotting, RT-PCR, flow cytometry, co-immunoprecipitation, and immunofluorescence were used to investigate the regulatory of taraxerone on SIRT1.

Results: Our study demonstrates for the first time that taraxerone can activate SIRT1 in macrophages, promoting SIRT1 activity. This activation inhibited the NF-κB signaling pathway primarily through the dephosphorylation and deacetylation of p65. Simultaneously, taraxerone disrupted the NLRP3 inflammasome signaling pathway, thereby alleviating M1 polarization of macrophages and mitigating sepsis-induced pulmonary inflammation and oxidative stress. In vivo, EX527 was used to validate the anti-inflammatory and anti-oxidative stress effects of taraxerone mediated by SIRT1.

Conclusion: SIRT1-mediated anti-inflammatory and anti-oxidative stress effects may be important targets for taraxerone in treating ALI.

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蒲公英萜酮通过激活 SIRT1 抑制 M1 极化并减轻败血症诱发的急性肺损伤。

背景：急性肺损伤（ALI）是与脓毒症相关的致死率最高的疾病，目前缺乏有效的药物治疗。巨噬细胞作为脓毒症诱导的急性肺损伤的主要细胞，会向促炎 M1 表型极化，并通过核因子卡巴-B（NF-κB）和 NLR 家族含吡咯啉结构域 3（NLRP3）炎性基因组信号通路分泌多种炎性细胞因子，加速疾病进程。中药景天的主要成分蒲公英萜酮具有多种生物活性。然而，蒲公英萜酮对脓毒症诱发的 ALI 的潜在保护作用仍不确定。本研究旨在探讨蒲公英萜酮对 ALI 的作用和机制：方法：通过盲肠结扎和穿刺建立 ALI 动物模型，并通过腹腔给药用蒲公英萜酮进行治疗。采用 H&E 染色、二氢乙啶染色、ELISA 试剂盒、细胞计数、髓过氧化物酶试剂盒、丙二醛试剂盒、谷胱甘肽试剂盒、超氧化物歧化酶试剂盒和流式细胞术分析他克塞隆对肺部的保护作用。Western印迹、RT-PCR、流式细胞术、共免疫沉淀和免疫荧光被用来研究蒲公英赛酮对SIRT1的调控作用：我们的研究首次证明了蒲公英萜酮能激活巨噬细胞中的 SIRT1，促进 SIRT1 的活性。这种激活主要通过 p65 的去磷酸化和去乙酰化来抑制 NF-κB 信号通路。同时，蒲公英萜酮还能破坏 NLRP3 炎性体信号通路，从而缓解巨噬细胞的 M1 极化，减轻败血症引起的肺部炎症和氧化应激。在体内，EX527被用来验证SIRT1介导的蒲公英萜酮的抗炎和抗氧化应激作用：结论：SIRT1介导的抗炎和抗氧化应激作用可能是蒲公英萜酮治疗ALI的重要靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chinese Medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY

CiteScore

7.90

自引率

4.10%

发文量

133

审稿时长

31 weeks

期刊介绍： Chinese Medicine is an open access, online journal publishing evidence-based, scientifically justified, and ethical research into all aspects of Chinese medicine. Areas of interest include recent advances in herbal medicine, clinical nutrition, clinical diagnosis, acupuncture, pharmaceutics, biomedical sciences, epidemiology, education, informatics, sociology, and psychology that are relevant and significant to Chinese medicine. Examples of research approaches include biomedical experimentation, high-throughput technology, clinical trials, systematic reviews, meta-analysis, sampled surveys, simulation, data curation, statistics, omics, translational medicine, and integrative methodologies. Chinese Medicine is a credible channel to communicate unbiased scientific data, information, and knowledge in Chinese medicine among researchers, clinicians, academics, and students in Chinese medicine and other scientific disciplines of medicine.