Ginsenoside Rd attenuates fine particulate matter-induced pulmonary inflammation by directly inhibiting the transforming growth factor-beta-activated kinase 1-mediated toll-like receptor 2 signaling

  • Phytomedicine. 2026 Jul 25:157:158318. doi: 10.1016/j.phymed.2026.158318.
Yu Na Song  1 ,  Su Hyeon Yun  2 ,  Seung-Hyung Kim  3 ,  Eun Sol Oh  4 ,  Hong-Hee Kim  2 ,  Hyung Won Ryu  4 ,  Soo Jin Oh  5 ,  Ji-Yoon Lee  5 ,  Sooil Kim  6 ,  Seunghoon Yang  7 ,  Jinhyuk Lee  7 ,  Hyunju Ro  8 ,  Sung-Tae Hong  9 ,  Su Ui Lee  10
Affiliations
  • 1. Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea; Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea.
  • 2. Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea; Department of Anatomy & Cell Biology, Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
  • 3. DJU Industry-University Cooperation Foundation, Daejeon University, Daejeon 34520, Republic of Korea.
  • 4. Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea.
  • 5. Asan Institute for Life Sciences, Asan Medical Center, Department of Pharmacology, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea.
  • 6. Department of Anatomy & Cell Biology, Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
  • 7. Bio-Design Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea; Department of Bioinformatics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
  • 8. Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea. Electronic address: [email protected].
  • 9. Department of Anatomy & Cell Biology, Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea. Electronic address: [email protected].
  • 10. Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea. Electronic address: [email protected].
PMID: 42177887 DOI: 10.1016/j.phymed.2026.158318
Abstract

Background: Particulate matter (PM) exposure is a major risk factor for the progression and exacerbation of inflammatory lung diseases. Ginsenoside Rd, a bioactive compound derived from Panax ginseng, has been reported to improve lung function; however, its effects on PM2.5 (PM less than 2.5 μm in diameter)-induced pulmonary inflammation and the underlying molecular mechanisms remain unclear.

Purpose: This study investigated whether ginsenoside Rd mitigates PM2.5-induced lung inflammation and explored its molecular targets in vitro and in vivo.

Methods: Mouse alveolar macrophages were stimulated with PM2.5, and mice were exposed to a PM10 and diesel exhaust particles mixture (PM/DEP) to evaluate the anti-inflammatory effects of ginsenoside Rd. Levels of TNF-α, IL-6, neutrophil Elastase, immune cell infiltration, Toll-like Receptor 2 (TLR2) expression, and transforming growth factor β-activated kinase 1 (TAK1) signaling were assessed. Histological staining was performed to examine lung tissue morphology. The direct interaction between Rd and TAK1 was also analyzed.

Results: In vitro, ginsenoside Rd reduced TNF-α, IL-6, and TLR2 expression by inhibiting TAK1-dependent activation of the IκB kinase (IKK)/nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase (ERK)/cAMP response element-binding protein (CREB) pathways. In vivo, Rd attenuated PM/DEP-induced lung tissue damage and neutrophil infiltration, thereby suppressing pulmonary inflammation via blockade of the TAK1/NF-κB pathway. Binding assays confirmed a direct interaction between Rd and TAK1, supporting its role as the key molecular target.

Conclusion: Ginsenoside Rd exerts protective effects against PM2.5-induced pulmonary inflammation by directly inhibiting TAK1-mediated TLR2 signaling. These findings suggest its potential as a therapeutic candidate for inflammatory lung diseases aggravated by air pollution.

Keywords
Air pollution; Ginsenoside Rd; NF-κB signaling pathway; Particulate matter 2.5 (PM2.5); TAK1 kinase; Toll-like receptor 2 (TLR2).
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