Oroxylum indicum and its flavonoids impact on SARS-CoV-2 and urban dust-induced inflammation in human lung fibroblast cells

Abstract

Background

SARS-CoV-2 infection and chronic urban dust exposure can lead to lung inflammation and fibrosis by stimulating pro-inflammatory cytokines. Oroxylum indicum (L.) Kurz and its flavonoids, baicalein and chrysin, demonstrate potential to treat pulmonary damage.

Purpose

This study evaluated the effects of O. indicum grilled fruit extract, baicalein, and chrysin against receptor-binding domain (RBD)- and urban dust-induced inflammation and key COVID-19 entry mechanisms using an in vitro human lung fibroblast model.

Methods

Human lung fibroblasts were exposed to RBD or urban dust. Relative gene expressions of TNF-α, IL-6, 5-LOX, ACE2, and TMPRSS2 were quantified. Enzyme-linked immunosorbent assay (ELISA) determined RBD–ACE2 binding inhibition. Computational analyses to explore potential mechanisms included PCA, molecular docking, and network pharmacology.

Results

Both RBD and urban dust dramatically increased genes, with RBD upregulating IL-6 and urban dust upregulating TNF-α. Dexamethasone suppressed them, validating the model. O. indicum extract, baicalein, and chrysin significantly reduced TNF-α, IL-6, and 5-LOX expression. O. indicum extract consistently downregulated ACE2 and TMPRSS2 expressions and decreased RBD and urban dust-induced inflammation. Baicalein and O. indicum extract inhibited RBD–ACE2 binding (IC₅₀ = 4.60 ± 0.7 µM and 435.4 ± 52.7 µg/ml, respectively). Experimental results were supported by computational analysis.

Conclusion

This research validates the in vitro model and demonstrates that O. indicum extract, baicalein, and chrysin have the potential to mitigate pulmonary inflammation and interfere with SARS-CoV-2 entry mechanisms. Further investigation should include protein-level analysis and in vivo studies confirming therapeutic efficacy.