Investigating the therapeutic mechanism of Bufei Decoction in COPD: Schisandrin B targets the TLR4/NF-κB/JAK-STAT signaling pathway

TL;DR

This study shows that Bufei Decoction, especially its component Schisandrin B, helps treat COPD by reducing lung damage and inflammation through a specific biological pathway.

Contribution

The study identifies Schisandrin B as a key therapeutic component in Bufei Decoction that targets the TLR4/NF-κB/JAK-STAT pathway in COPD.

Findings

Bufei Decoction dose-dependently improved lung function and reduced inflammation in COPD rats.

Schisandrin B strongly binds to TLR4 and inhibits the NF-κB/JAK-STAT pathway, reducing lung injury and macrophage activation.

TLR4 knockdown reversed the protective effects of Schisandrin B, confirming its role in the therapeutic mechanism.

Abstract

Evaluate Bufei Decoction effects on chronic obstructive pulmonary disease (COPD) and elucidate Schisandrin B (Sch B) mechanism via TLR4 pathway.

COPD was induced in rats using LPS/cigarette smoke. Effects of low, medium, high-dose Bufei Decoction and doxofylline were assessed on lung pathology, function, blood gases, and inflammation. Sch B role was investigated via network pharmacology (identifying active components/targets), molecular docking (schisandrin B-TLR4 binding), and in vivo validation.

Bufei Decoction dose-dependently ameliorated COPD-induced lung injury, improved pulmonary function/blood gases, and reduced inflammation (high-dose most effective). Network pharmacology identified 241 Bufei Decoction components (including Sch B) targeting core molecules (TLR4, JAK1, STAT3). Molecular docking confirmed strong Sch B-TLR4 binding. Functional analysis implicated immune/inflammatory pathways. In vivo experiments showed that Sch B dose-dependently alleviated lung injury, improved pulmonary function, reduced the levels of inflammatory markers, and inhibited the M1/M2 macrophage ratio as well as the expression of proteins related to the NF-κB/JAK-STAT signaling pathway. Crucially, TLR4 knockdown reversed Sch B’s protective effects, worsening injury and inflammation.

Bufei Decoction treats COPD through multi-component synergy. Sch B is a key active component, exerting therapeutic effects by targeting TLR4 to regulate macrophage polarization and inhibit the NF-κB/JAK-STAT signaling pathway, thereby improving lung function and reducing inflammation.

The online version contains supplementary material available at 10.1186/s41065-025-00629-8.

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