Supplementary file 1_Efficacy and mechanisms of andrographolide derivative in acute exacerbations of chronic obstructive pulmonary disease: a meta-analysis, network pharmacology, molecular docking, and in vitro validation study.docx

Inflammatory markers were also reduced: CRP [MD = −4.72 mg/L, 95% CI -6.83 to –2.61], WBC [MD = −1.30 ×10⁹/L, 95% CI −1.79 to −0.80], NEUT% [MD = −4.36 percentage points, 95% CI -6.18 to −2.54], PCT [MD = −0.17 ng/mL, 95% CI -0.23 to −0.10] (all P < 0.0001). Network pharmacology identified 39 overlapping targets, highlighting TNF, IL-1β, NLRP3, and CASP1 as core targets. Molecular docking suggested energetically favorable predicted interactions of andrographolide with NLRP3, caspase-1, IL-1β, and IL-18.

In vitro, andrographolide enhanced BEAS-2B cell viability, reduced LDH release, and suppressed NLRP3, caspase-1, IL-1β, and TNF-α expression.</p>Conclusion<p>Andrographolide derivative injections as adjunctive therapy may improve clinical response, pulmonary function, oxygenation, and inflammatory status in patients with AECOPD. Mechanistic experiments using the parent compound andrographolide suggest that these therapeutic effects are potentially mediated by the NLRP3/caspase-1/IL-1β inflammatory axis.

Nevertheless, these findings should be interpreted cautiously given the exclusively Chinese single-center RCTs, substantial heterogeneity in some outcomes, and lack of direct mechanistic data on individual derivatives.</p>