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.

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.