2. Academic Validation
  3. Qi-Sai-Er-Sang-Dang-Song decoction inhibits pyroptosis and inflammation in THP-1 cells and alleviates rheumatoid arthritis by inhibiting the NLRP3-pyroptosis signaling pathway

Qi-Sai-Er-Sang-Dang-Song decoction inhibits pyroptosis and inflammation in THP-1 cells and alleviates rheumatoid arthritis by inhibiting the NLRP3-pyroptosis signaling pathway

  • Phytomedicine. 2025 Oct 27:148:157481. doi: 10.1016/j.phymed.2025.157481.
Jia Liu 1,  Tianru Wang 2,  Bojun Tang 2,  Xing Fu 3,  Nengqiao Fang 2,  Hanyu Lu 1,  Zhengyang Yu 2,  Yi Zhang 4,  Jinsong Su 5
Affiliations

Affiliations

  • 1 Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 2 State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
  • 3 Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 4 Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: zhangyi@cdutcm.edu.cn.
  • 5 Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: sujinsong@cdutcm.edu.cn.
PMID: 41172917 DOI: 10.1016/j.phymed.2025.157481
Abstract

Background: Rheumatoid arthritis (RA) is the most common chronic and autoimmune disease characterised by synovial hyperplasia, pannus formation and bone destruction, and accompanied with multiple complications. Qi-Sai-Er-Sang-Dang-Song decoction (QSD) is commonly prescribed for the clinical treatment of RA in Tibetan medicine, featuring remarkable therapeutic efficacy and few side effects. Nevertheless, its mechanism of action in RA treatment is unclear.

Purpose: The study aims to elucidate the components of QSD, and explore the mechanism of QSD's anti-RA effect through in vivo and in vitro experiments.

Methods: QSD and QSD-containing serum were respectively determined by UPLC-LTQ-XL-MSn and UPLC-Q-Exactive Orbitrap MS. A collagen-induced arthritis (CIA) rat model was used to investigate the anti-RA effects of QSD in vivo. The pharmacological was evaluated by body mass, foot swelling rate, immune organ index and hematoxylin-eosin (H&E) staining. Pyroptosis and inflammation were detected by TUNEL staining, western blotting and ELISA. THP-1 cells were induced by LPS combined with ATP to establish an in vitro inflammation model. Inflammatory mediators were detected by ELISA. Cell Pyroptosis was examined by flow cytometry, LDH release, scanning electron microscopy, western blotting, and immunofluorescence.

Results: MS analysis was conducted on QSD and QSD-containing serum to clarify the material basis and active components of QSD. In vivo, QSD could effectively improve RA symptoms in CIA rats; significantly reduce the expression levels of NLRP3-pyroptosis pathway-related proteins; and inhibit the release of IL-1β, IL-6 and IL-18 in serum. In vitro, QSD could inhibit the release of inflammatory factors IL-6 and IL-1β. QSD could also inhibit the activation of NLPR3 inflammasomes, suppress Pyroptosis, reduce LDH release and minimise the expression levels of proteins related to the NLRP3-pyroptosis pathway.

Conclusion: QSD exerts therapeutic effects on RA by regulating the NLRP3-pyroptosis pathway through the inhibition of Pyroptosis and NLRP3 inflammasome activation. Therefore, QSD can be further developed and applied clinically as a new drug for RA treatment.

Keywords

CIA rat model; NLRP3-pyroptosis; Qi-Sai-Er-Sang-Dang-Song-Tang; Rheumatoid arthritis.

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