Evidence map›Paper›PMID 40669599›Full record

ArticleJournal of advanced research2026

Tussilagone attenuated cigarette smoke-induced chronic obstructive pulmonary disease through regulating Nrf2 and NF-κB/NLRP3 inflammasome via directly targeting cysteine 434 of KEAP1.

Lin-Tao Xu, Qing-Tong Han, Zhen-Peng Xu, Xiao-Ning Wang, Hua Zhang, Tao Shen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Lin-Tao XuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong University, Jinan 250012, China; Key Lab of Chemical Biology (MOE), Shandong Engineering Research Center for Traditional Chinese Medicine Standard, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Shandong Provincial Key Laboratory of Bioactive Components and Translational Research of Traditional Chinese Medicine, Shandong University, Jinan 250012, China.
Qing-Tong HanState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong University, Jinan 250012, China; Key Lab of Chemical Biology (MOE), Shandong Engineering Research Center for Traditional Chinese Medicine Standard, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Shandong Provincial Key Laboratory of Bioactive Components and Translational Research of Traditional Chinese Medicine, Shandong University, Jinan 250012, China. Electronic address: hanqingtong@sdu.edu.cn.
Zhen-Peng XuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong University, Jinan 250012, China; Key Lab of Chemical Biology (MOE), Shandong Engineering Research Center for Traditional Chinese Medicine Standard, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Shandong Provincial Key Laboratory of Bioactive Components and Translational Research of Traditional Chinese Medicine, Shandong University, Jinan 250012, China.
Xiao-Ning WangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong University, Jinan 250012, China; Key Lab of Chemical Biology (MOE), Shandong Engineering Research Center for Traditional Chinese Medicine Standard, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Shandong Provincial Key Laboratory of Bioactive Components and Translational Research of Traditional Chinese Medicine, Shandong University, Jinan 250012, China.
Hua ZhangSchool of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: bio_zhangh@ujn.edu.cn.
Tao ShenState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong University, Jinan 250012, China; Key Lab of Chemical Biology (MOE), Shandong Engineering Research Center for Traditional Chinese Medicine Standard, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Shandong Provincial Key Laboratory of Bioactive Components and Translational Research of Traditional Chinese Medicine, Shandong University, Jinan 250012, China. Electronic address: shentao@sdu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionChronic obstructive pulmonary disease (COPD) represents a significant global health challenge, characterized by substantial morbidity and mortality rates. In traditional Chinese medicine (TCM), Farfarae Flos (FF) has been widely utilized as a therapeutic agent for COPD. However, its specific bioactive compounds and the underlying mechanisms are unclear.

objectivesThis study aims to identify bioactive constituent of FF against COPD and illustrate its therapeutic target and mechanism. METHODS AND

resultsIn this research, a high-throughput screening on constituents of FF was conducted, leading to the identification of a potent anti-COPD lead, tussilagone (TUS). Utilizing biotin-labeling approach, Kelch-like ECH-associated protein 1 (KEAP1), the ubiquitin E3 ligase of nuclear factor erythroid 2-related factor 2 (Nrf2), was identified to be the direct target of TUS. Mechanistically, TUS activated KEAP1-Nrf2 axis by covalent modification of cysteine 434 (Cys434), a novel high-reactivity cysteine of KEAP1. TUS-mediated Nrf2 activation further suppressed the activation of nuclear factor kappa-B (NF-κB) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, consequently attenuating lung inflammation in COPD.

conclusionTUS was identified as the bioactive constituent of FF against COPD, which directly targeted Cys434 of KEAP1. KEAP1 was proven to be a pharmacological target for the treatment of COPD, and Cys434 was identified to be the first highly reactive cysteine in Kelch domain of KEAP1. TUS inhibits lung inflammation by regulating Nrf2 and NF-κB/NLRP3, which is the mechanism of FF against COPD.

Indexed as

InflammasomesKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2NLR Family, Pyrin Domain-Containing 3 ProteinPulmonary Disease, Chronic ObstructiveTussilagoAnimalsCigarette SmokingCysteineDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLNF-kappa BSignal TransductionCysteineInflammasomesKEAP1 protein, humanKeap1 protein, mouseKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNfe2l2 protein, mouseNF-E2-Related Factor 2NF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseChronic obstructive pulmonary diseaseInflammationKEAP1Tussilagone

Identifiers

PMID40669599
PMCPMC13001054

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.