Tong Sai granule improves AECOPD via regulation of MAPK-SIRT1-NF-κB pathway and cellular senescence alleviation

Tao, Ling; Lu, Xin; Fu, Zihao; Tian, Yange; Liu, Xinguang; Li, Jiansheng; Zhao, Peng

doi:10.1016/j.jep.2023.116622

Cited by 7 publications

(1 citation statement)

References 45 publications

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“…Besides, traditional Chinese medicine (TCM) has gained growing attention as a potential treatment for COPD, owing to its multi-target and multi-pathway action mechanisms, which distinguish it from Western medicines. 73 , 74 Notably, monomer compounds derived from TCM hold significant potential as valuable assets for the discovery of innovative reagents, given their exceptional biological activity and greater structural diversity in comparison to synthetic compounds. 75 In addition to the general advantages of monomers, AGP possessed the advantageous characteristics of low toxicity, ease of acquisition, and cost-effectiveness, rendering it extensively utilized in the treatment of diverse inflammatory conditions.…”

Section: Discussionmentioning

confidence: 99%

Andrographolide Attenuates NLRP3 Inflammasome Activation and Airway Inflammation in Exacerbation of Chronic Obstructive Pulmonary Disease

Yu,

Miao,

Xiao

et al. 2024

DDDT

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Purpose The aim of this study is to uncover the anti-inflammatory propertity of andrographolide (AGP) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the underlying mechanisms related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway. Methods An in vivo experiment was conducted on murine model of AECOPD through endotracheal atomization of elastase and lipopolysaccharide (LPS). Intraperitoneal AGP was administered four times. NLRP3 inflammasome pathway molecules were examined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. By using enzyme-linked immunosorbent assay (ELISA), we tested interleukin (IL)-1β levels in bronchoalveolar lavage fluid. An in vitro study was conducted to determine how AGP impacts the NLRP3 inflammasome in THP-1 derived macrophages. The levels of molecules involved in the pathway were measured. Furthermore, molecular docking analyses were carried out to investigate the interactions between AGP and pathway targets. Results In the in vivo study, NLRP3 inflammasome activation was observed in mice experiencing AECOPD. The administration of high-dose AGP demonstrated a mitigating effect on inflammatory cells infiltration in the lungs. Moreover, AGP administration effectively suppressed the expression of NLRP3, apoptosis associated speck-like protein that contains a CARD (PYCARD), cysteinyl aspartate-specific protease-1 (Caspase-1), IL-1β, and IL-18 at both the genetic and protein levels. In the in vitro experiment, IL-1β levels were significantly elevated in THP-1 derived macrophages with activated inflammasome compared to the control group. Furthermore, the downregulation of NLRP3, CASP1, and IL1B genes was observed upon the inhibition of NLRP3 expression through small interfering RNA (siRNA). AGP demonstrated inhibitory effects on the gene expression and protein levels of NLRP3, Caspase-1, and IL-1β. Additionally, molecular docking analysis confirmed that AGP exhibited a favorable binding affinity with all five targets of the pathway. Conclusion AGP effectively inhibited NLRP3 inflammasome activation and mitigated the inflammatory reaction of AECOPD both in animal models and in vitro experiments, highlighting the potential of AGP as a treatment for AECOPD with anti-inflammatory properties.

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Section: Discussionmentioning

confidence: 99%