Anti-inflammatory effects of Rhus javanica ethanol extract for pulmonary and colonic disorders

Rhus javanica is a traditional medicinal herb widespread in East Asia, including Korea, China, and Japan. Valued for its antidiarrheal, bactericidal, and anti-inflammatory properties, it epitomizes the synergy of traditional wisdom and natural benefits.

This study aimed to investigate the anti-inflammatory properties of Rhus javanica ethanol extract (Rj-EE) in both in vitro and in vivo models, elucidate the underlying mechanisms, and provide a theoretical foundation for its potential use as a natural therapeutic option for clinical colitis and lung diseases.

RAW264.7 cells, peritoneal macrophages, HEK293T cells, and mouse models of acute lung injury and acute ulcerative colitis were used to evaluate the anti-inflammatory activity of Rj-EE.

In this study, the phytochemical constituents of Rj-EE were identified by GC-MS and LC-MS. Inflammatory targets were sourced from GeneCards and Swiss Target Prediction databases. Gene ontology and KEGG analyses revealed Rj-EE's anti-inflammatory mechanisms. Nitric oxide (NO) production and cell viability were assessed with Griess and MTT assays, respectively. Inflammatory cytokines were measured by RT-PCR, transcription factor activity by luciferase assays, and protein expression through Western blotting. Overexpression and CETSA assays were conducted in HEK293T cells. In vivo model animals with lipopolysaccharide-induced acute lung injury and dextran sulfate sodium-induced acute ulcerative colitis were treated with Rj-EE and then assessed by RT-PCR, hematoxylin and eosin (H&E), cytokine analysis via an enzyme-linked immunosorbent assay, and Western blotting.

KEGG analysis identified the NF-κB pathway as key to Rj-EE's anti-inflammatory effects, with Src as a central target. Molecular docking showed strong binding between Rj-EE's active components and key genes. In vitro, Rj-EE reduced NO production and inflammatory mRNA markers, and inhibited MyD88- and TRIF-induced NF-κB and AP-1 activity. It also targeted Src and Syk. In vivo, Rj-EE alleviated colitis and lung injury.

Overall, Our findings lay a foundation for further research into Rj-EE's molecular anti-inflammatory mechanisms and suggest that Rhus javanica could be explored as a potential anti-inflammatory agent targeting Src and Syk for conditions like lung injury and colitis.