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

Background: 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.

Purpose: 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.

Study Design: 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.

Methods: 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.

Results: 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.

Conclusion: 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.