1. Academic Validation
  2. Qimai Feiluoping decoction inhibits mitochondrial complex I-mediated oxidative stress to ameliorate bleomycin-induced pulmonary fibrosis

Qimai Feiluoping decoction inhibits mitochondrial complex I-mediated oxidative stress to ameliorate bleomycin-induced pulmonary fibrosis

  • Phytomedicine. 2023 Apr:112:154707. doi: 10.1016/j.phymed.2023.154707.
Lu Ding 1 Yingying Yang 2 Zeyu Wang 1 Hang Su 1 Yaxin Li 3 Jing Ma 4 Tingting Bao 5 Hongyu Qi 1 Siyu Song 1 Jing Li 1 Jiachao Zhao 3 Ziyuan Wang 4 Daqing Zhao 1 Xiangyan Li 6 Linhua Zhao 7 Xiaolin Tong 8
Affiliations

Affiliations

  • 1 Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China.
  • 2 National Center for Integrated Traditional and Western Medicine, China-Japan Friendship Hospital, Beijing China; Graduate College, Beijing University of Chinese Medicine, Beijing, China.
  • 3 College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun 130017, China.
  • 4 College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China.
  • 5 Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
  • 6 Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China. Electronic address: [email protected].
  • 7 Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China; Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China. Electronic address: [email protected].
  • 8 Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China. Electronic address: [email protected].
Abstract

Background: Qimai Feiluoping decoction (QM), a Traditional Chinese Medicine formula, has been included in rehabilitation program for functional disorders of discharged COVID-19 patients. QM has been proved to effectively improve the clinical symptoms and imaging signs of PF in COVID-19 convalescent patients.

Purpose: This study to explore the pharmacological effect of QM against PF from the perspectives of imaging, pathological staining, and molecular mechanisms, and identify possible active components.

Methods: Micro-CT imaging and immunohistochemical staining were investigated to verify the therapeutic effect of QM in the bleomycin (BLM)-induced PF mouse model. The 4D-label-free proteomics analysis of lung tissues was then conducted to explore the novel mechanisms of QM against PF, which were further validated by a series of experiments. The possible components of QM in plasma and lung tissues were identified with UHPLC/IM-QTOF-MS analysis.

Results: The results from micro-CT imaging and pathological staining revealed that QM treatment can inhibit BLM-induced lung injury, extracellular matrix accumulation and TGF-β expression in the mouse model with PF. The 4D-label-free proteomics analysis demonstrated that the partial subunit proteins of mitochondrial complex I and complex II might be potential targets of QM against PF. Furthermore, QM treatment can inhibit BLM-induced mitochondrial ROS content to promote ATP production and decrease oxidative stress injury in the mouse and cell models of PF, which was mediated by the inhibition of mitochondrial complex I. Finally, a total of 13 protype compounds and 15 metabolites from QM in plasma and lung tissues were identified by UHPLC/IM-QTOF-MS, and liquiritin and isoliquiritigenin from Glycyrrhizae radix et rhizoma could be possible active compounds against PF.

Conclusion: It concludes that QM treatment could treat PF by inhibiting mitochondrial complex I-mediated mitochondrial oxidated stress injury, which could offer new insights into the pharmacological mechanisms of QM in the clinical application of PF patients.

Keywords

Active components; COVID-19; Mitochondrial complex I; Oxidated stress; Pulmonary fibrosis; Qimai Feiluoping decoction.

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