Tao-He-Cheng-Qi decoction protects against sepsis-associated acute lung injury by modulating gut microbiota and succinate-associated pulmonary macrophage polarization.

IF 6.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2026-10-21 DOI:10.1016/j.jep.2026.122520

Wanhua Huo, Xuyang Hou, Yiying Huang, Zuming Li, Xueru Chen, Jieni Feng, Yunqi Kong, Simin Pan, Qiuyue Wang, Jian Xu, Jiankun Chen, Jiqiang Li, Rongyuan Yang, Yue Lu, Yuntao Liu

{"title":"Tao-He-Cheng-Qi decoction protects against sepsis-associated acute lung injury by modulating gut microbiota and succinate-associated pulmonary macrophage polarization.","authors":"Wanhua Huo, Xuyang Hou, Yiying Huang, Zuming Li, Xueru Chen, Jieni Feng, Yunqi Kong, Simin Pan, Qiuyue Wang, Jian Xu, Jiankun Chen, Jiqiang Li, Rongyuan Yang, Yue Lu, Yuntao Liu","doi":"10.1016/j.jep.2026.122520","DOIUrl":null,"url":null,"abstract":"Ethnopharmacological relevance: Sepsis-associated acute lung injury (SA-ALI) has high mortality and limited therapies.Tao-He-Cheng-Qi decoction protects against sepsis-associated acute lung injury by modulating gut microbiota and succinate-associated pulmonary macrophage polarization.Aim of the study: To evaluate the protective effects of THCQ pretreatment against LPS-induced SA-ALI and examine associated changes in gut microbiota, succinate levels, SUCNR1-PKA-CREB signaling and macrophage polarization.Materials and methods: A murine SA-ALI model was induced by intraperitoneal LPS. Lung injury, inflammatory cytokines (IL-1β, TNF-α), and M1/M2 polarization were assessed. Gut microbiota was analyzed by 16S rRNA sequencing. Succinate levels, SUCNR1, and PKA-CREB signaling were measured. Microbiota dependence was tested using antibiotic depletion, fecal microbiota transplantation (FMT) from THCQ-treated donors, exogenous succinate, and macrophage depletion with clodronate liposomes.Results: THCQ pretreatment attenuated lung injury, reduced IL-1β and TNF-α levels, and shifted pulmonary macrophage polarization toward an M2-like phenotype. These effects were accompanied by altered gut microbiota composition, a lower abundance ratio of bacterial families grouped in the exploratory succinate-metabolism analysis, reduced serum and pulmonary succinate levels, lower SUCNR1 expression, and increased PKA/CREB phosphorylation. Antibiotic treatment attenuated the protective responses to THCQ, while FMT from THCQ-treated donors reproduced improvements in lung injury. Exogenous succinate attenuated THCQ-mediated protection. Clo-Lipo treatment reduced the proportions of alveolar and interstitial macrophages and markedly attenuated the protective effects of THCQ.Conclusion: THCQ treatment protects against SA-ALI and suppresses M1-like macrophage polarization. These effects are accompanied by changes in gut microbiota composition, reduced succinate levels, and altered SUCNR1-PKA-CREB signaling. Together, the findings support a role for gut microbiota-metabolism-immune interactions in the protective effects of THCQ.","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122520"},"PeriodicalIF":6.8000,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2026.122520","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Ethnopharmacological relevance: Sepsis-associated acute lung injury (SA-ALI) has high mortality and limited therapies.Tao-He-Cheng-Qi decoction protects against sepsis-associated acute lung injury by modulating gut microbiota and succinate-associated pulmonary macrophage polarization.

Aim of the study: To evaluate the protective effects of THCQ pretreatment against LPS-induced SA-ALI and examine associated changes in gut microbiota, succinate levels, SUCNR1-PKA-CREB signaling and macrophage polarization.

Materials and methods: A murine SA-ALI model was induced by intraperitoneal LPS. Lung injury, inflammatory cytokines (IL-1β, TNF-α), and M1/M2 polarization were assessed. Gut microbiota was analyzed by 16S rRNA sequencing. Succinate levels, SUCNR1, and PKA-CREB signaling were measured. Microbiota dependence was tested using antibiotic depletion, fecal microbiota transplantation (FMT) from THCQ-treated donors, exogenous succinate, and macrophage depletion with clodronate liposomes.

Results: THCQ pretreatment attenuated lung injury, reduced IL-1β and TNF-α levels, and shifted pulmonary macrophage polarization toward an M2-like phenotype. These effects were accompanied by altered gut microbiota composition, a lower abundance ratio of bacterial families grouped in the exploratory succinate-metabolism analysis, reduced serum and pulmonary succinate levels, lower SUCNR1 expression, and increased PKA/CREB phosphorylation. Antibiotic treatment attenuated the protective responses to THCQ, while FMT from THCQ-treated donors reproduced improvements in lung injury. Exogenous succinate attenuated THCQ-mediated protection. Clo-Lipo treatment reduced the proportions of alveolar and interstitial macrophages and markedly attenuated the protective effects of THCQ.

Conclusion: THCQ treatment protects against SA-ALI and suppresses M1-like macrophage polarization. These effects are accompanied by changes in gut microbiota composition, reduced succinate levels, and altered SUCNR1-PKA-CREB signaling. Together, the findings support a role for gut microbiota-metabolism-immune interactions in the protective effects of THCQ.

查看原文本刊更多论文

桃和承气汤通过调节肠道菌群和琥珀酸相关的肺巨噬细胞极化来预防败血症相关的急性肺损伤。

民族药理学相关性：败血症相关急性肺损伤（SA-ALI）具有高死亡率和有限的治疗方法。桃和承气汤通过调节肠道菌群和琥珀酸相关的肺巨噬细胞极化来预防败血症相关的急性肺损伤。研究目的：评价THCQ预处理对lps诱导的SA-ALI的保护作用，并检测肠道菌群、琥珀酸水平、SUCNR1-PKA-CREB信号通路和巨噬细胞极化的相关变化。材料与方法：腹腔注射LPS建立小鼠SA-ALI模型。观察肺损伤、炎症因子（IL-1β、TNF-α）和M1/M2极化。采用16S rRNA测序分析肠道菌群。测量琥珀酸盐水平、SUCNR1和PKA-CREB信号。微生物群依赖性测试采用抗生素耗竭、经thcq处理的供体粪便微生物群移植（FMT）、外源性琥珀酸盐和氯膦酸脂质体巨噬细胞耗竭。结果：THCQ预处理可减轻肺损伤，降低IL-1β和TNF-α水平，使肺巨噬细胞极化向m2样表型转变。这些影响伴随着肠道菌群组成的改变，探索性琥珀酸代谢分析中分组的细菌家族丰度比降低，血清和肺琥珀酸水平降低，SUCNR1表达降低，PKA/CREB磷酸化增加。抗生素治疗减弱了对THCQ的保护反应，而来自THCQ治疗供体的FMT在肺损伤方面得到了改善。外源性琥珀酸盐减弱thcq介导的保护作用。Clo-Lipo处理降低了肺泡和间质巨噬细胞的比例，显著减弱了THCQ的保护作用。结论：THCQ对SA-ALI有保护作用，可抑制m1样巨噬细胞极化。这些影响伴随着肠道微生物群组成的变化，琥珀酸盐水平的降低和SUCNR1-PKA-CREB信号的改变。总之，这些发现支持了肠道微生物群-代谢-免疫相互作用在THCQ保护作用中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.