Pharmacological basis of Codonopsis Radix in COPD: Lobetyolin modulates Nrf2/NF-κB-mediated inflammation and oxidative stress.

2026-02-14
Journal of ethnopharmacology 363
- Zhengjun Chen
- Qi Shi
- Chunxia Wang
- Zhihong Zhang
- Jie Yang
- WenRong Luo
- Fude Yang

PubMed: 41698557
DOI: 10.1016/j.jep.2026.121383

Study Design

Population: Male SPF-grade C57BL/6J mice and BEAS-2B cells
Methods: CSE/LPS-induced COPD model in mice, UHPLC-QE-MS combined with network pharmacology, HPLC, and CSE/LPS-induced BEAS-2B cell injury model
Funding: Unclear

Ethnopharmacological relevance

Codonopsis Radix (CR), a traditional Chinese medicinal herb, tonifies the lung and promotes fluid production. It serves as an effective and commonly used remedy for pulmonary diseases. Chronic obstructive pulmonary disease (COPD) is a common respiratory disease in which inflammation and oxidative stress are central to disease pathogenesis. Lobetyolin (LBT), a bioactive constituent of CR, exhibits anti-inflammatory and antioxidant activities; however, its efficacy and underlying mechanisms in COPD remain unclear.

Aim of the study

This study aims to identify the active components of Wen Codonopsis Radix (WCR) for the treatment of COPD, and to elucidate the mechanism by which LBT alleviates COPD by regulating the Nrf2/NF-κB signaling pathway.

Materials and methods

Male SPF-grade C57BL/6J mice were used to establish a CSE/LPS-induced COPD model. The active fraction of WCR was screened by pharmacodynamic evaluation. Potential active components and signaling pathways within the most effective fraction were predicted using UHPLC-QE-MS combined with network pharmacology. Candidate bioactive constituents were further quantified by HPLC to substantiate their chemical relevance. In a CSE/LPS-induced BEAS-2B cell injury model, the mechanism of LBT was investigated with a focus on the Nuclear factor erythroid 2-related factor 2 (Nrf2)/Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway.

Results

The ethyl acetate fraction of WCR alleviated CSE/LPS-induced lung injury in COPD mice, and LBT emerged as a potential active component for COPD treatment. In CSE/LPS-induced BEAS-2B cells, LBT significantly reduced inflammation and oxidative stress, modulated the Nrf2/NF-κB pathway, upregulated SOD expression, and decreased IL-8, TNF-α, and MDA levels. Collectively, these effects attenuated COPD development and progression.

Conclusion

LBT alleviates inflammation and oxidative stress, delays COPD progression, and ameliorates lung injury by activating Nrf2, inhibiting NF-κB signaling, and restoring Nrf2/NF-κB homeostasis. This study provides a theoretical basis for elucidating the "quality-effect" relationship of WCR and supports its product development.