Modulation of Cytokine Imbalance by Phaleria macrocarpa Leaf Extract in LPS-stimulated RAW 264.7 Macrophages

Chronic inflammation is strongly associated with excessive production of pro-inflammatory cytokines. Mahkota Dewa (Phaleria macrocarpa) is a traditional medicinal plant recognized for its anti-inflammatory potential. Nevertheless, its specific role in modulating pro- and anti-inflammatory cytokines within immune cells remains inadequately explored. This study aimed to investigate the anti-inflammatory activity of P. macrocarpa leaf extract by assessing its regulatory effects on pro-inflammatory (IFN-γ and TNF-α) and anti-inflammatory cytokines (IL-10 and TGF-β) in RAW 264.7 macrophage cells stimulated with lipopolysaccharide (LPS). The cells were treated with P. macrocarpa leaf extract at 9, 18, and 36 µg/mL, none of which exhibited cytotoxic effects. Cytokine levels were measured using flow cytometry. The findings demonstrated a significant reduction (p<0.05) in IFN-γ and TNF-α levels at 18 and 36 µg/mL of P. macrocarpa leaf extract. Furthermore, IL-10 levels increased in a dose-dependent manner, while the highest TGF-β expression was observed at 18 µg/mL. The findings revealed that P. macrocarpa leaf extract exerts significant anti-inflammatory effects by modulating cytokine production in LPS-induced macrophages. These results suggest its broader therapeutic potential in managing inflammation-related diseases, warranting further molecular and clinical investigation.