---
title: "Seco-tanapartholide B activates PKM2 to reprogram glycolysis and reduce acute lung injury"
id: "pubmed-42208465"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42208465"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42208465/"
doi: "10.1016/j.bioorg.2026.110040"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Seco-tanapartholide B activates PKM2 to reprogram glycolysis and reduce acute lung injury
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42208465
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42208465/)
- **DOI:** [10.1016/j.bioorg.2026.110040](https://doi.org/10.1016%2Fj.bioorg.2026.110040)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study reports that **seco-tanapartholide B (SB)**, a sesquiterpene lactone from Artemisia argyi, reduces inflammation and glycolysis in models of **acute lung injury (ALI)** induced by lipopolysaccharide (LPS). - SB was shown to directly bind and activate **PKM2**, identified using thermal proteome profiling (TPP), CETSA, DARTS, and BLI target-engagement assays. - LC-MS/MS mapping indicated a covalent modification of PKM2 at **Cys424** via SB’s α-methylene-γ-lactone moiety, which enhanced pyruvate kinase activity and promoted PKM2 tetramer formation. - Activation and tetramerization of PKM2 by SB correlated with suppression of **glycolysis** and downregulation of inflammation-associated signaling pathways, including NF-κB and STAT3, and reduced HIF-1α expression. - Genetic knockdown of PKM2 diminished SB’s anti-inflammatory and glycolysis-inhibitory effects in macrophages, supporting on-target activity. - The authors propose SB as a natural **PKM2 activator** that links metabolic reprogramming to anti-inflammatory effects and suggest PKM2 tetramerization as a therapeutic strategy for ALI/ARDS. - The work extends the potential application of PKM2 activators beyond oncology into inflammatory lung disease and provides biochemical evidence for covalent activation of PKM2 by a plant-derived compound. - Details on experimental models, dosing, quantitative outcomes, and safety data were not reported in the abstract and require consultation of the full text for specifics.
## Clinical Analysis & Structured Key Points
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Epub 2026 May 26. # Seco-tanapartholide B ameliorates acute lung injury by covalently activating PKM2 and reprogramming glycolytic metabolism [Dongrong Zhu](https://pubmed.ncbi.nlm.nih.gov/?term=Zhu+D&cauthor_id=42208465)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#full-view-affiliation-1 "School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy \(Tianjin\), Tianjin's Clinical Research Center for Cancer, Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China. Electronic address: dongr_zhu@email.tjut.edu.cn."), [Lirong Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+L&cauthor_id=42208465)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#full-view-affiliation-2 "School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China."), [Yue Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+Y&cauthor_id=42208465)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#full-view-affiliation-2 "School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China."), [Linnan Du](https://pubmed.ncbi.nlm.nih.gov/?term=Du+L&cauthor_id=42208465)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#full-view-affiliation-2 "School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China."), [Dingqiao Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+D&cauthor_id=42208465)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#full-view-affiliation-3 "Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, People's Republic of China."), [Peng Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+P&cauthor_id=42208465)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#full-view-affiliation-2 "School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China."), [Sha Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+S&cauthor_id=42208465)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#full-view-affiliation-4 "Tianjin Key Laboratory of Drug Targeting and Bioimaging, Life and Health Intelligent Research Institute, Tianjin University of Technology, Tianjin, 300384, People's Republic of China. Electronic address: shaliu@tjut.edu.cn."), [Liren Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+L&cauthor_id=42208465)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#full-view-affiliation-5 "National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy \(Tianjin\), Tianjin's Clinical Research Center for Cancer, Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China. Electronic address: liuliren@tmu.edu.cn.") Affiliations Expand ### Affiliations * 1 School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy (Tianjin), Tianjin's Clinical Research Center for Cancer, Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China. Electronic address: dongr_zhu@email.tjut.edu.cn. * 2 School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China. * 3 Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, People's Republic of China. * 4 Tianjin Key Laboratory of Drug Targeting and Bioimaging, Life and Health Intelligent Research Institute, Tianjin University of Technology, Tianjin, 300384, People's Republic of China. Electronic address: shaliu@tjut.edu.cn. * 5 National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy (Tianjin), Tianjin's Clinical Research Center for Cancer, Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China. Electronic address: liuliren@tmu.edu.cn. * PMID: **42208465** * DOI: [ 10.1016/j.bioorg.2026.110040 ](https://doi.org/10.1016/j.bioorg.2026.110040) Item in Clipboard # Seco-tanapartholide B ameliorates acute lung injury by covalently activating PKM2 and reprogramming glycolytic metabolism Dongrong Zhu et al. Bioorg Chem. 2026. Show details Display options Display options Format Abstract PubMed PMID Bioorg Chem Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Bioorg+Chem%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Bioorg+Chem%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42208465/) . 2026 Sep 5:179:110040. doi: 10.1016/j.bioorg.2026.110040. Epub 2026 May 26. ### Authors [Dongrong Zhu](https://pubmed.ncbi.nlm.nih.gov/?term=Zhu+D&cauthor_id=42208465)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#short-view-affiliation-1 "School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy \(Tianjin\), Tianjin's Clinical Research Center for Cancer, Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China. Electronic address: dongr_zhu@email.tjut.edu.cn."), [Lirong Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+L&cauthor_id=42208465)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#short-view-affiliation-2 "School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China."), [Yue Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+Y&cauthor_id=42208465)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#short-view-affiliation-2 "School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China."), [Linnan Du](https://pubmed.ncbi.nlm.nih.gov/?term=Du+L&cauthor_id=42208465)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#short-view-affiliation-2 "School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China."), [Dingqiao Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+D&cauthor_id=42208465)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#short-view-affiliation-3 "Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, People's Republic of China."), [Peng Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+P&cauthor_id=42208465)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#short-view-affiliation-2 "School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China."), [Sha Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+S&cauthor_id=42208465)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#short-view-affiliation-4 "Tianjin Key Laboratory of Drug Targeting and Bioimaging, Life and Health Intelligent Research Institute, Tianjin University of Technology, Tianjin, 300384, People's Republic of China. Electronic address: shaliu@tjut.edu.cn."), [Liren Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+L&cauthor_id=42208465)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42208465/#short-view-affiliation-5 "National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy \(Tianjin\), Tianjin's Clinical Research Center for Cancer, Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China. Electronic address: liuliren@tmu.edu.cn.") ### Affiliations * 1 School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy (Tianjin), Tianjin's Clinical Research Center for Cancer, Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China. Electronic address: dongr_zhu@email.tjut.edu.cn. * 2 School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China. * 3 Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, People's Republic of China. * 4 Tianjin Key Laboratory of Drug Targeting and Bioimaging, Life and Health Intelligent Research Institute, Tianjin University of Technology, Tianjin, 300384, People's Republic of China. Electronic address: shaliu@tjut.edu.cn. * 5 National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy (Tianjin), Tianjin's Clinical Research Center for Cancer, Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China. Electronic address: liuliren@tmu.edu.cn. * PMID: **42208465** * DOI: [ 10.1016/j.bioorg.2026.110040 ](https://doi.org/10.1016/j.bioorg.2026.110040) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Acute lung injury (ALI) is a life-threatening inflammatory condition with limited therapeutic options. Metabolic reprogramming, particularly PKM2-mediated glycolysis, plays a pivotal role in inflammatory responses, yet natural activators targeting this pathway remain largely unexplored. Herein, we found that seco-tanapartholide B (SB), a sesquiterpene lactone derived from the medicinal and edible herb Artemisia argyi, suppresses inflammation and glycolysis both in vitro and in vivo, thereby alleviating lipopolysaccharide (LPS)-induced ALI. Using thermal proteome profiling (TPP), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and bio-layer interferometry (BLI), we identified PKM2 as the direct molecular target of SB. LC-MS/MS analysis further revealed that SB covalently binds to Cys424 of PKM2 through its α-methylene-γ-lactone moiety, leading to enhanced pyruvate kinase activity and promoted PKM2 tetramerization. Consequently, this modification suppressed glycolysis as well as inflammation-related pathways, including NF-κB and STAT3 signaling, and reduced HIF-1α expression. Additionally, genetic knockdown of PKM2 attenuates the anti-inflammatory and glycolysis-inhibitory effects of SB in macrophages. Collectively, these findings identify SB as a natural PKM2 activator that therapeutically targets metabolic-inflammatory crosstalk in ALI. This study extends the potential application of PKM2 activators beyond oncology to inflammatory lung diseases and provides a biochemical rationale for promoting PKM2 tetramerization as a therapeutic strategy for ALI/acute respiratory distress syndrome (ARDS). **Keywords:** ALI/ARDS; Glycolysis; Metabolic reprogramming; PKM2; Sesquiterpene lactone. Copyright © 2024. Published by Elsevier Inc. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Iso-seco-tanapartholide from Artemisia argyi inhibits the PFKFB3-mediated glycolytic pathway to attenuate airway inflammation in lipopolysaccharide-induced acute lung injury mice. ](https://pubmed.ncbi.nlm.nih.gov/36195302/) Kong M, Zhu D, Dong J, Kong L, Luo J.Kong M, et al.J Ethnopharmacol. 2023 Jan 30;301:115781. doi: 10.1016/j.jep.2022.115781. Epub 2022 Oct 3.J Ethnopharmacol. 2023.PMID: 36195302 * [ Covalent targeting GAPDH by Pudilan formula and baicalein suppresses macrophage Warburg effect to alleviate acute lung injury. ](https://pubmed.ncbi.nlm.nih.gov/41506101/) Jiang M, Yang Y, Zhang Y, Zhang P, Zhang Q, Yang T, Zhang G, Zhou J, Chu Z, Li S, Wang Y, Zhang J, Shen S, Song P, Wang J, Tang H.Jiang M, et al.Phytomedicine. 2026 Feb;151:157727. doi: 10.1016/j.phymed.2025.157727. Epub 2025 Dec 21.Phytomedicine. 2026.PMID: 41506101 * [ Ailanthone ameliorates CCl4-induced liver fibrosis by targeting PKM2-mediated macrophage M1 polarization and glycolytic reprogramming. ](https://pubmed.ncbi.nlm.nih.gov/41980396/) Wan Y, Wang T, Wang K, Huo Q, Cheng X.Wan Y, et al.Int Immunopharmacol. 2026 Jun 15;179:116640. doi: 10.1016/j.intimp.2026.116640. Epub 2026 Apr 13.Int Immunopharmacol. 2026.PMID: 41980396 * [ The role of the interplay between macrophage glycolytic reprogramming and NLRP3 inflammasome activation in acute lung injury/acute respiratory distress syndrome. ](https://pubmed.ncbi.nlm.nih.gov/39623879/) Luo L, Zhuang X, Fu L, Dong Z, Yi S, Wang K, Jiang Y, Zhao J, Yang X, Hei F.Luo L, et al.Clin Transl Med. 2024 Dec;14(12):e70098. doi: 10.1002/ctm2.70098.Clin Transl Med. 2024.PMID: 39623879Free PMC article.Re
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