Terminalia chebula Fruit Extract Ameliorates Peripheral Edema by Inhibiting NF-κB and MAPK Signaling Pathways

Peripheral edema is a pathological condition caused by abnormal fluid accumulation in the interstitial space due to elevated vascular permeability and inflammation. This study evaluated the therapeutic efficacy of <i>Terminalia chebula</i> fruit extract (TCE) in inflammation-induced peripheral edema and clarified its molecular mechanisms. Using hydrogen peroxide (H₂O₂)-stimulated human umbilical vein endothelial cells (HUVECs), TCE was tested for effects on cell viability, inflammatory gene expression, intracellular reactive oxygen species, endothelial barrier integrity, and vascular endothelial growth factor (VEGF)-induced migration. Its influence on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling was examined. In vivo, TCE was assessed in acetic acid-induced peritoneal vascular permeability and carrageenan-induced paw edema models, followed by histological analysis and serum tumor necrosis factor-α (TNF-α) measurement. TCE restored cell viability (76.2% to 94.8%), reduced <i>TNF</i>, <i>IL6</i>, and <i>PTGS2</i> mRNA expression, and decreased reactive oxygen species by 27.2%. It enhanced barrier integrity, increased transendothelial electrical resistance, and inhibited VEGF-induced migration. TCE suppressed NF-κB and MAPK activation. In vivo, TCE reduced Evans blue extravasation by 41.6% and paw edema by 67.5%. Histology showed reduced dermal thickening and inflammatory infiltration, and serum TNF-α levels were lowered. TCE attenuates peripheral edema by preserving endothelial barrier function and suppressing inflammatory signaling, supporting its potential as a therapeutic agent for inflammation-associated vascular dysfunction and edema.