The formation of advanced glycation end product (AGE) is a risk factor for diabetic retinopathy. Since the current treatment for diabetic retinopathy is accompanied by side effects, preliminary findings have suggested Peperomia pellucida (L.) Kunth as a potential alternative therapeutic option for diabetic retinopathy. This study aimed to elucidate the anti-inflammatory mechanism of P. pellucida in the AGE-stimulated human retinal pigment epithelial cell line ARPE-19. Phytochemical analysis revealed phenylpronanoids, terpenes, and fatty acids in P. pellucida. Through in vitro cell viability assay, the P. pellucida methanolic extract (IC50 = 8.70 mg/mL) and ethyl acetate fraction (IC50 = 7.34 mg/mL) were considered as non toxic for ARPE-19. AGE induced an inflammatory response in ARPE-19 by upregulating the gene (2.4-5.8-fold) and protein (1.4-2.3-fold) expression of signal transducer and activator of transcription 3 (STAT3), interleukin-8 (IL-8), monocyte chemoattractant protein-1, matrix metalloproteinase 2, and vascular endothelial growth factor. At 1.5 mg/mL, P. pellucida methanolic extract suppressed IL-8 expression (p
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