Chronic obstructive pulmonary disease (
COPD) is a serious chronic
lung disease.
Schisandrin A (SchA) is one of the most important active ingredients in Schisandra chinensis and has been used to treat various
lung diseases in several countries. Here, we studied the pharmacological effect of SchA on airway
inflammation induced by cigarette
smoke (CS) and explored the therapeutic mechanism of SchA in
COPD model mice. Our results showed that SchA treatment significantly improved the lung function of CS-induced
COPD model mice and reduced the recruitment of leukocytes and hypersecretion of
interleukin-6 (IL-6), interleukin-1β (IL-1β) and
tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF). H&E staining showed that SchA treatment could effectively reduce
emphysema, immune cell infiltration and airway wall destruction. In addition, we found that SchA treatment can stimulate the expression of
heme oxygenase-1 (HO-1) through the nuclear factor-erythroid 2-related factor (Nrf2) pathway, significantly reduce oxidative stress, increase
catalase (CAT) and
superoxide dismutase (SOD) levels, and suppress the level of
malondialdehyde (MDA) in
COPD model mice. Moreover, SchA treatment suppressed the generation of the NLRP3/ASC/Caspase1
inflammasome complex to inhibit the inflammatory response caused by IL-1β and
IL-18 and pyroptosis caused by GSDMD. In conclusion, our study shows that SchA treatment can inhibit the production of ROS and the activation of the NLRP3
inflammasome by upregulating Nrf-2, thereby producing anti-inflammatory effects and reducing
lung injury in
COPD model mice. More importantly, SchA exhibited similar anti-inflammatory effects to
dexamethasone in
COPD model mice, and we did not observe substantial side effects of SchA treatment. The high safety of SchA makes it a potential candidate drug for the treatment of
COPD.