1. Academic Validation
  2. Schisandrin A regulates the Nrf2 signaling pathway and inhibits NLRP3 inflammasome activation to interfere with pyroptosis in a mouse model of COPD

Schisandrin A regulates the Nrf2 signaling pathway and inhibits NLRP3 inflammasome activation to interfere with pyroptosis in a mouse model of COPD

  • Eur J Med Res. 2023 Jul 3;28(1):217. doi: 10.1186/s40001-023-01190-8.
Jiamin Zeng # 1 2 Sida Liao # 1 Zhu Liang 1 2 Caiping Li 2 Yuewen Luo 2 Kexin Wang 2 Dapeng Zhang 1 Lan Lan 1 Suzhen Hu 3 Wanyan Li 1 Ran Lin 4 Zichen Jie 4 Yuanlong Hu 1 2 Shiting Dai 1 2 Zhimin Zhang 5
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 2 Guangzhou Medical University, Guangzhou, China.
  • 3 Huangdao District Chinese Medicine Hospital, Qingdao, China.
  • 4 The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 5 The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. zhangzhimin51666@163.com.
  • # Contributed equally.
Abstract

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.

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