2. Academic Validation
  3. Kaempferol reprograms pro-inflammatory macrophage polarization by targeting the PTGS2-PGE2 axis: A multi-omics deconvolution of a traditional anti-inflammatory herb pair

Kaempferol reprograms pro-inflammatory macrophage polarization by targeting the PTGS2-PGE2 axis: A multi-omics deconvolution of a traditional anti-inflammatory herb pair

  • Biochem Pharmacol. 2026 Jun:248:117865. doi: 10.1016/j.bcp.2026.117865.
Han Chen 1,  Shuying Chen 1,  Haixia Huang 1,  Kai Chen 2,  Huimin Wan 3,  Ruifen Zhang 4,  Linya Wu 4,  Qifang Wu 4,  Haibin Tong 5,  Gang Xu 6
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 2 Department of Gynecology, Woman's Hospital School of Medicine Zhejiang University, Hangzhou 310006, China.
  • 3 Department of Obstetrics, Woman's Hospital School of Medicine Zhejiang University, Hangzhou 310006, China.
  • 4 College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China.
  • 5 College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Beijing 100700, China. Electronic address: [email protected].
  • 6 Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: [email protected].
PMID: 41794261 DOI: 10.1016/j.bcp.2026.117865
Abstract

Metabolic dysfunction-associated steatohepatitis (MASH), a progressive liver disease driven by pro-inflammatory (M1) macrophage polarization, lacks effective pharmacotherapies. While the Chaihu-Baishao (CB) herb pair is a traditional remedy for liver disorders, its molecular mechanism is unknown. This study aimed to deconstruct CB's mechanism and validate its core bioactive component for MASH therapy. We employed an integrative strategy from multi-omics to in vivo validation. Transcriptomic analysis identified M1-polarized macrophages as central drivers of MASH. We then demonstrated that the CB extract ameliorates MASH pathology in a diet-induced mouse model. To elucidate the underlying mechanism, network pharmacology predicted kaempferol as the core bioactive compound and PTGS2 (COX-2) as its primary target. A direct kaempferol-PTGS2 interaction was rigorously confirmed by a suite of biophysical assays (CETSA, DARTS, MST), yielding a dissociation constant (Kd) of 5.16 µM. Functionally, kaempferol suppressed M1 macrophage polarization in vitro by inhibiting PTGS2-mediated prostaglandin E2 (PGE2) production, an effect reversed in a PGE2 rescue experiment. Crucially, in vivo administration of kaempferol alone recapitulated the therapeutic benefits of the full CB extract, significantly improving liver pathology and suppressing hepatic PGE2 levels. Our study provides a multi-scale validation, identifying kaempferol as the principal bioactive component of the CB herb pair. Kaempferol ameliorates MASH by directly targeting the PTGS2-PGE2 axis to reprogram macrophage polarization, presenting a promising, mechanism-defined therapeutic lead with clear translational potential.

Keywords

Chaihu-Baishao; Kaempferol; Macrophage polarization; Metabolic dysfunction associatedsteatohepatitis (MASH); Network pharmacology; PTGS2 (COX-2).

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