2. Academic Validation
  3. Xuanfei Baidu Decoction suppresses complement overactivation and ameliorates IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway

Xuanfei Baidu Decoction suppresses complement overactivation and ameliorates IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway

  • Phytomedicine. 2023 Jan:109:154551. doi: 10.1016/j.phymed.2022.154551.
Caixia Li 1,  Yuhong Li 2,  Han Zhang 2,  Yuzhen Zhuo 1,  Lanqiu Zhang 1,  Lei Yang 1,  Qiaoying Gao 1,  Zhengwei Tu 1,  Rui Shao 2,  Yu Wang 2,  Junhua Zhang 2,  Lihua Cui 3,  Shukun Zhang 4
Affiliations

Affiliations

  • 1 Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Tianjin Nankai Hospital; Nankai Clinical College, Tianjin Medical University, Tianjin 300100, China.
  • 2 Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 3 Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Tianjin Nankai Hospital; Nankai Clinical College, Tianjin Medical University, Tianjin 300100, China. Electronic address: [email protected].
  • 4 Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Tianjin Nankai Hospital; Nankai Clinical College, Tianjin Medical University, Tianjin 300100, China. Electronic address: [email protected].
PMID: 36610119 DOI: 10.1016/j.phymed.2022.154551
Abstract

Background: The significant clinical efficacy of Xuanfei Baidu Decoction (XFBD) is proven in the treatment of patients with coronavirus disease 2019 (COVID-19) in China. However, the mechanisms of XFBD against acute lung injury (ALI) are still poorly understood.

Methods: In vivo, the mouse model of ALI was induced by IgG immune complexes (IgG-IC), and then XFBD (4g/kg, 8g/kg) were administered by gavage respectively. 24 h after inducing ALI, the lungs were collected for histological and molecular analysis. In vitro, alveolar macrophages inflammation models induced by IgG-IC were performed and treated with different dosage of XFBD-containing serum to investigate the protective role and molecular mechanisms of XFBD.

Results: The results revealed that XFBD mitigated lung injury and significantly downregulated the production of pro-inflammatory mediators in lung tissues and macrophages upon IgG-IC stimulation. Notably, XFBD attenuated C3a and C5a generation, inhibited the expression of C3aR and C5aR and suppressed the activation of JAK2/STAT3/SOCS3 and NF-κB signaling pathway in lung tissues and macrophages induced by IgG-IC. Moreover, in vitro experiments, we verified that Colivelin TFA (CAF, STAT3 Activator) and C5a treatment markedly elevated the IgG-IC-triggered inflammatory responses in macrophages and XFBD weakened the effects of CAF or C5a.

Conclusion: XFBD suppressed complement overactivation and ameliorated IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway. These data contribute to understanding the mechanisms of XFBD in COVID-19 treatment.

Keywords

Acute lung injury; Complement; IgG immune complex; JAK2/STAT3; NF-κB; XFBD.

Figures
Products
Inhibitors & Agonists