Na LiJi-Lin ChenYi-Jian SunJia-Fan SunTing-Hua Wang0000-0002-9831-4395Amy Yi Hsan, SaikSaikAmy Yi Hsan0000-0002-1882-7757Alan Ong Han Kiat2026-10-192026-10-192025-08-0810.1007/s11418-025-01935-1https://dspace-cris.utar.edu.my/handle/123456789/11791The objective of this study is to investigate the protective effects of berberine (BBR) on diabetic retinopathy (DR) and its regulatory mechanism on NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway. DR rat model was established by Streptozotocin (STZ) injection and treated with BBR. Retinal structure was evaluated by Optical Coherence Tomography (OCT), Hematoxylin and Eosin (HE) staining, and immunofluorescence. NLRP3 pathway proteins were detected by Western blot (WB), and the effects were further studied using RNA interference. BBR significantly improved retinal structure in DR rats and decreased the expression of NLRP3, Cysteine-aspartic acid protease-1(Caspase-1), Gasdermin D (GSDMD), Interleukin-1 beta (IL-1?), and Interleukin-18 (IL-18) (p < 0.05). In an in vitro study using human RPE cells line, BBR administration improved cell viability and reduced RPE pyroptosis, while RNA interference of NLRP3 pathway enhanced BBR’s protective effects. BBR ameliorates DR by inhibiting NLRP3 inflammasome-mediated pyroptosis pathway. © The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy 2025.en-USBerberineDiabetic retinopathyPyroptosisRetinal protectionAnimalsCaspase 1Cell LineDiabetes MellitusExperimentalDiabetic RetinopathyHumansInflammasomesInterleukin-18Interleukin-1betaMaleNLR FamilyPyrin Domain-Containing 3 ProteinRatsSprague-Dawleyberberinecryopyrineosingasdermingasdermin dglucosehematoxylininflammasomeinterleukin 18interleukin 1betainterleukin 1beta converting enzymestreptozocinunclassified drugNlrp3 proteinratanimal cellanimal experimentanimal modelanimal tissueArticlecell structurecell viabilitycontrolled studydiabetic retinopathyglucose blood levelhumanhuman cellimmunofluorescencemalenonhumanoptical coherence tomographyprotein expressionpyroptosisrat modelretina epithelial cellRNA interferencesignal transductionstreptozotocin-induced diabetes mellitusTUNEL assayWestern blottinganimalcell linedrug effectdrug therapyexperimental diabetes mellitusgeneticsmetabolismSprague Dawley ratjournal-article